Document V3J2XER0Vx4896qJp9KzEw5Kj

FILE NAME Talc TALC DATE 2000 Dec 1 DOC TALC175 DOCUMENT DESCRIPTION Letter to Dr. Mary Wolfe Duke University RE Comments on the Subcommittee's Consideration of Listing Talc in the 10th Report on Carcinogens Divte 4 of Occupational & Environmental Medicine Dec. Dec. 2000 Duke University Medical Center Department of Community & Family Medicine Division of Occupational & Environmental Medicine Box 3834 Durham NC 27710 December 1 2000 Tel 919-286-5744 FAX 919-286-5647 Dr. Mary S. Wolfe National Toxicology Program Board of Scientific Counselors Report on Carcinogens Subcommittee NIEHS A3-07 Research Triangle Park NC 27709 Re Comments on the Subcommittee's Consideration of Listing Tale in the 10th Report on Carcinogens Dear Dr. Wolfe My comments are being made on the behalf of the Art and Creative Materials Institute a profit trade organization that represents the major manufacturers and importers of art materials in the United States Tale is a common component of these art materials I would like to address several issues discussed in the draft Report on Carcinogens Background Document for Talc Asbestiform and Asbestiform These comments are offered to the Report on Carcinogens Subcommittee with the expectation that this report can be strengthened if it addresses certain issues in more detail I will comment on both on studies concerning both asbestiform and nonasbestiform tale Asbestiform Talc Definition The draft report discusses the definition of asbestiform fibers It would be strengthened if it includes NIOSH's definition of these fibers NIOSH Kullman et al 1995 defines asbestiform habit as a specific type of mineral fibrosity in which the growth is primarily in one dimension and the crystals form naturally as long flexible fibers Fibers can be found in bundles that can be easily separated into smaller bundles or ultimately into fibrils This definition is important since many of the fibers in asbestiform tale are cleavage fragments NIOSH's definition for asbestiform habit contrasts with their definition for the nonasbestiform habit : http/ 72 14 203 search vKzb3nEaXCSJ duk_nd Pneumoconiosis 1 of 4/12/2006 1 31 24 PM Division of Occupational & Environmental Medicine These minerals have ... crystal habits where growth proceeds in two or three dimensions instead of one dimension When milled these minerals do not break into fibrils but rather into fragments resulting from cleavage along the two or three growth planes Particles formed by the comminution of these minerals are referred to as cleavage fragments Respirable fiber size Although the draft report notes that a respirable fiber has a diameter of 3-4 m this is for fibers with a density of 1. Talc has a specific gravity of 3 and consequently the equivalent aerodynamic diameter of respirable tale fibers would be 1/3 of this on the order of 1 m Wylie et al 1993 This finding is particularly important in that the fibers in asbestiform tale are primarily wider than 1 m with only 10-11 of fibers in commercial talcs being < m in diameter Fiber size and cancer risk There are excellent animal models for the relationship between fiber dimension and risk of both mesothelioma and lung cancer For mesothelioma risk fibers with a dimension of /0.25 im n diameter and 8 m long appear to present the greatest risk Stanton et al 1981 Oehlert 1991 with almost no risk presented by short fibers Davis et al 1986 Most amphibole fibers in a asbestiform tale mine are shorter than 10 m Kelse and Thompson 1989 and would not be expected to present a risk of mesotheliomas Similarly lung cancer risk also depends on fiber dimensions Based on asbestos inhalation studies Berman et al 1995 found that potency for lung cancer rested with fibers that were longer than 10 m and less than 0.3 m in diameter Their model found that fibers that were 10 m long and had widths from 0.3-5.0 m were not associated with a lung cancer risk Lippmann 1988 performed as similar analysis He found that fiber retention drops rapidly as fiber diameter increases from 0.8 to 2.0 m No lung cancer risk was associated with fiber length less than 5 m Lung cancer risk was associated with fibers with a diameter of 0.3-0.8 m and a substantial fraction 10 m in length Animal Studies Although IARC considered a number of studies involving the carcinogenicity of talc in experimental animals they did not have access to identification information concerning several of the fibrous talcs This is particularly important because talcs form the Grouvenor Tale Company GTC the mine most studied for cancer risk have been examined in a number of animal models and have been found to be carcinogenic Stanton et al 1981 examined two asbestiform talcs from the Grouvenor tale district including one from GTC Stanton tale 6 in their pleural implantation rat model Neither of these talcs induced mesotheliomas although based on particle dimensions a 60 incidence of mesotheliomas would have been expected with the GTC tale Oehlert 1991 analyzed the Stanton data breaking out potency assessments not only by particle size but by mineral type When compared to asbestos the author found that tales were 135,000 as potent for causing pleural tumors This analysis included both the asbestiform talcs and 5 asbestiform tales studied by Stanton et al Smith et al 1979 also studied one GTC tale FD14 FD14 in their hamster pleural mesothelioma model This tale as well as another tale containing amphibole fibers was negative in their model Wylie et al 1997 studied the FD1FD144 tale from the Smith et al study in an in vitro system It was not cytotoxic and did not induce cell proliferation Talc samples not containing quartz were not cytotoxic where asbestos was both cytotoxic and induced proliferation Epidemiology asbestiform amphiboles The primary components of asbestiform talcs other than talc are cleavage fragments of anthophyllite and tremolite Since exposure to these cleavage fragments may be a factor in cancer risk from exposure to asbestiform talc a review of epidemiological studies of workers exposed to nonasbestiform amphiboles is in order and will strengthen this report Kusiak et al 1991 looked at a cohort of 54128 gold and nickel miners with potential exposure to nonasbestiform amphibole fibers They found an excess cancer risk in 1945 workers but no relationship between cancer excess and exposure to mineral fibers The concluded that the excess was probably related to exposures to arsenic and radon decay products radon daughters Steenland and Brown 1995 studied 3328 gold miners from South Dakota There was no significant increase in lung cancer r.sk in this cohort though there was evidence of excessive quartz exposure including elevated deaths from immunological diseases renal disease and tuberculosis The authors suggest that a slight excess in lung cancer rates might be related to the smoking habits of miners they smoke more then the general population Cooper et al 1992 studied 3444 taconite miners exposed to silica and nonasbestiform amphibole fibers The standardized mortality rate SMR for lung cancer was less than expected at 67 and was not related to duration of employment exposure level or latency When Cooper et al eliminated those workers with less than 3 months of employment from the analysis the SMR for lung cancer actually decreased as duration of employment increased Epidemiology asbestiform tale The association between exposure to asbestiform tale and lung cancer risk is primarily based on the findings of increased cancer risk in workers exposed to asbestiform tale in the Grouvenor tale district GTD of upstate New http 72 14 203 search vKzb3nEaXCSJ duk Pneumoconiosis 2 of 4/12/2006 1 31 24 PM Division of Occupational & Environmental Medicine York A more detailed description of these studies as well as inclusion of the latest Dezell et al 1995 study would be in order Kleinfeld et al 1967 1974 found a 10 pulmonary and pleural tumors among a study of all GTD workers All cases occurred in workers who were exposed prior to the introduction of exposure control measures ca. 1945. Twenty of the workers died of pneumoconioses including 5 who died ofa complication of quartz exposure tuberculosis This study had the short coming that it did not take into account exposures other then to did not take into account smoking history and did not relate exposure levels to outcome Recent data developed by NIOSH 1980 can be used to estimate respirable quartz exposures to workers in this study NIOSH found that for the average dust exposure of 2.9 million particles per cubic foot mppcf in GTC mills the average respirable quartz exposure was 11 mand that for the average dust exposure of 8.1 mppcf in the GTC mine the average quartz exposure was 12.4 g mDust exposure measurements were made for GTD mines and mills in the Kleinfeld et al study These exposures can be translated to average respirable quartz exposures as follows . wwwwwww 1945 Mppcf 1945-196 1945-19655 Qartz m3 Mppcf Quartz wwwwwwwwww Mines drilling = 818 1250 5 Mines other 129 5-9 Mills 69-278 260-1050 27-37 m 8 8-14 102-14 102-140 0 102-140 Exposure levels prior to 1945 were sufficiently high in both mines and mills to result in the pneumoconioses cases described above with quartz levels in air as great as 10 fold higher than today's permissible exposure limit for respirable quartz of 100 m Respirable quartz is a known human lung carcinogen with elevated risks particularly when exposures are sufficient to result in silicosis That respirable quartz exposures were a concern has been confirmed by autopsy studies performed by Dr. Jerrold Abraham of 8 GTD workers Two of the 5 workers with a history of more than 20 years of tale mining had silicosis The second study that has been used to implicate a risk between exposure to asbestiform tale and lung cancer is the NIOSH 1979 study of Grouvenor Tale Company workers GTC went into operation in the late 1940's using a wet drilling method that would have suppressed exposure to respirable quartz dust as noted in the above table The NIOSH study has been criticized because of a number of short comings It would be important to highlight these short comings since they have been addressed in later epidemiological studies of these workers Specific concerns with this study included its small size inclusion of all workers including those that had only worked days lack of assessment of the contribution of prior exposures no study of exposure cancer relationsh ps and no adjustment for smoking effects Brown et al 1983 Any prior mine work among GTC employees would have likely involved high level exposures to quartz dust Stille and Tabershaw 1982 were able to nearly double the size of the cohort They found that the SMR for lung cancer among workers who had only worked at GTC was less than expected 76 and that tuberculosis a disease associated with silicosis was a significant finding SMR 680 This study did not correct for smoking history exposure or identify GTC exposures that many have been a concern Lamm et al 1988 presented a analysis ofthe Stille and Tabershaw 1982 data set in which the occupat onal histories of workers dying of lung cancer were presented 8 of 11 workers who died of lung cancer had worked in mines other than tale mines or in quaries elsewhere than at GTC The SMR for lung cancer in mill workers was 72 for those workers who had worked at least one year at GTC For those for workers who worked less than one year and had first worked to GTC 20-24 years prior to their death the SMR for lung cancer was 1111. The latter group would have included workers with prior exposures to mine dust prior to the putting in place ofdust control technologies Gamble 1993 performed a nested case control study on NIOSH's second evaluation of 710 GTC workers NIOSH 1990 to address concerns of confounding They found that when using fellow GTC workers as controls all of the excess lung cancer risk could be ascribed to smoking When looking at past exposures they found that essentially all tale exposure could be ascribed to work at GTC They were able to give more complete exposure histories for the lung cancer cases 8 of the 22 cases had worked as drillers at mines or quarries other than GTC and 17 had worked in metal mines prior to working at GTC Work in mines would have been expected to be associated with exposure to either quartz dust exposures would have likely been even higher in metal mines than in tale mines because of quartz content of base rock or radon daughters a known cause of excess lung cancer risk in metal miners That drillers may be at particular risk of quartz exposure has been noted by Rubino et al 1976 who found that dust generated from drilling operations my http 72 14 203 search vKzb3nEaXCSJ duk Pneumoconiosis 3 of 4/12/2006 1 31 24 PM > Division Division of Occupational & Environmental Medicine contain up to 18 quartz even though tale itself is relatively free from quartz In metal mines drilling dust can contain up to 39 quartz McDonald et al 1978 Dezell et al 1995 further expanded the cohort to 818 workers and increased the latency time to an average of 21 years for GTC workers They were able to address the concern that prior studies did not address incorporate an exposure analysis by estimating respirable dust exposures When compared to past dust measurements there was an excellent correlation between the two with a correlation coefficient of 0.78 They found no relationship between dust exposure at GTC and lung cancer Increases in lung cancer were limited to workers hired prior to 1955 with deaths from malignant respiratory disease concentrated in this group as well When adjusting for exposure they found an inverse relationship between lung cancer and exposure to all subjects to those workers who were first employed prior to 1955 and to those workers who had worked at GTC for more than one year The Gamble and Dezell et al studies discount the finding of an exposure risk of lung cancer for GTC workers with smoking and prior exposures to causing quartz dust or radon being likely contributors to the risk asbestiform Talc Lung overload Your Committee's concern with cancer risk from exposure to asbestiform tale rests in part on the finding of lung cancers in female rats exposed to greater than 18 mg of platy tale in an NTP assay This assessment would be strengthened with a more complete discussion of overload of alveolar macrophage AM clearance lung clearance that can contribute to both lung cancer risk in rats and lung inflammation as seen in this study When there is overload of lung clearance by inert particles irreversible inflammation and even an increased cancer risk occurs This has been documented in rat exposure studies involving carbon black diesel soot titanium dioxide toner and PVC spheres Oberdorster 1995a Such effects occur when particle deposition is such that AM can no longer keep the particle lung burden constant at a given dose With sufficiently high exposures lung clearance inhibition and associated lung inflammation is irreversible even after exposure ceases Bellman et al 1992 Inhibition of lung clearance and associated inflammation results in DNA and sister chromatid changes in lung epithelial cells Lung inflammation is thought to be the reason for increased cancer risk in lung overload conditions Although the Report discounts lung clearance as a mechanism for the finding of lung cancer in female rats in the NTP study this overlooks the strong likelihood that lung overload was involved in the noted outcome Oberdorster 1995b found that lung clearance was markedly inhibited in both rats and mice in this study Based upon the expected particle retention half life talc lung burden in rats was increased by a factor of 5-6.5 fold and in mice by a factor of 9.4 to 21.6 fold at 24 months Without inhibition of lung clearance no increase in tale lung burden would have been expected Bronchiolar lavage studies done by NTP at this time confirmed the level of inflammation was what would be expected from the effects of lung clearance overload not a specific toxic effect such as seen with respirable quartz Goodman 1995 a member of the Scientific Board of Counselors evaluating this chronic tale inhalation study , concurred with Oberdorster that the maximum tolerated dose for this study was exceeded He noted that platy tale was not genotoxic Capron et al 1990 and that the chronic toxicity and inflammation in female rats was substantially higher than in males or mice where no tumors were noted Animal studies The NTP ttaallee study is not supported by other studies of the carcinogenic potential of tale in experimental systems Stenback et al 1978 injected USP platy tale into the trachea of hamsters and found no respiratory tract tumors Lesions seen were similar to those seen with treatment with iron dust Capron et al 1990 injected fiber talc into the pleural space of 52 Sprague rats No pleural tumors occurred during their life span Asbestos served as a positive control Stanton et al 1981 examined the carcinogenicity of 7 talcs in their rat intrapleural assay None of these talcs caused a higher frequency of tumors than seen in the study's control population Oehlert 1991 analyzed the Stanton data breaking out potency assessments not only by particle size but by mineral type When compared to asbestos the author found that talcs were 135,000 as potent for causing pleural tumors Five of these talcs were asbestiform Epidemiological studies The report discounts the follow up study of patients treated intrapleurally with tale Research Committee of the British Thoracic Association and the Medical Research Council Unit 1979 because the tale was not identified and follow up intervals were less than 15 years The pleural cavity appears to be particularly sensitive to the carcinogenic effects of minerals in the animal model This experiment is therefore particularly cogent Although talc types were not identified European Pharmacopea talcs which would have likely included talcs used for this purpose have been analyzed Paoletti et al 1984 and included both fibrous as well as platy talcs Eighty of the patients where followed for 15-30 years and 75 for 30-40 years a duration http 72 14 203 search vKzb3nEaXCSJ duk Pneumoconiosis 4 of 4/12/2006 1 31 24 PM Division of Occupational & Environmental Medicine sufficiently long to have identified any cancer risk from such a procedure Selvan et al 1979 found that the relative risk of lung cancer among millers exposed to platy tale was 1.0 but elevated in miners They discounted this association because miners can be exposed to radon daughters Wergeland et al 1990 also found that cancer risk among tale millers working with fiber tale was not elevated They also explained a slight increase in lung cancer risk among miners as likely secondary to radon daughter exposure Radon daughter exposure level in the studied mine was 10 fold higher than in the tale mine in the Selvan et al study In summary the assessment of cancer risk of asbestiform and asbestiform tale be strengthened by Addressing issues of risk associated with fiber size associated cancer risk is not seen with the small fiber lengths that predominate in the GTC mine and mill Because exposures were qualitatively similar to those at other mines and mills in the region Brown et al 1983 this relationship is particularly important for assessing the exposure relationships in the cohort studies on which your Committee bases there cancer risk concern Including information on source in the description of tale animal studies A number of studies have been made of the GTD talcs all negative for cancer risk This finding is particularly important since the positive epidemiological studies for asbestiform talc are related to exposures to and other dust from this region Including in the assessment a review of epidemiological studies of lung cancer risk none associated with exposure to nonasbestiform cleavage fragments This is particularly cogent since the major fiber burden in GTD talcs is from such cleavage fragments Including a discussion of exposure relationships in the epidemiological assessment of asbestiform tale cancer risk This is particularly pertinent since there is major confounding in the worker segment of these studies by not adjusting for risks of lung cancer from smoking and exposures to respirable quartz dust which has also been associated with human lung cancer risk A detailed assessment of exposure has not found a relationship between asbestiform talc exposure and increased lung cancer risk e Including in the assessment a more detailed discussion of confounding by lung overload in the NTP talc inhalation study Lung overload with inert particles is associated with lung inflammation and cancer risk Significant lung overload occurred in both rats and mice in this study associated with both inflammation and lung cancer at the highest exposure level That the cancer risk was likely associated with lung overload mechanisms needs to be addressed Comparing the potency of tale to asbestos in animal models An updated assessment of the Stanton et al study of talcs found that asbestos was 135000 fold more potent than the talcs that they studied These talcs included both asbestiform and non- asbestiform talcs Although asbestiform tale contains fibers these do not appear to behave like asbestos This animal model does not provide biological support for the NTP asbestiform tale study findings Addressing the similarities between human tale pleurodesis and the rodent intrapleural model The finding of no tumor risk in long term follow up of patients treated with pleurodesis lends support to the negative findings with tale in the animal model Respectfully submitted http 72 14 203 search vzb3nEaXCSJ duk Pneumoconiosis 5 of 4/12/2006 1 31 24 PM DIVISION of Occupational & Environmental Medicine Woodhall Stopford MD MSPH References AbrahamJL Abestosis talcosis mesothelioma and commercial amphibole asbestos fibers and cleavage fragments in lung tissues of New York State miners abstract Presented to OSHA in their asbestos standard hearings 1990 Bellmann B Muhle H Creutzenberg O Mermelstein R. Irreversible pulmonary changes induced in rat lung by dust overload Environ Health Perspect 1992 189-91 Berman DW Crump KS Chatfield EJ Davis JM Jones AD The sizes shapes and mineralogy of asbestos structures that induce lung tumors or mesothelioma in HAN rats following inhalation Risk Anal 1995 Apr 181-95 Bischoff F Bryson G. Tale at the rodent intrathoracic intraperitoneal and subcutaneous sites Proc Am Assoc Cancer Res 17 1976 Brown DP Beaumont JJ Dement JM The toxicity of update New York talc Letter to the editor With response by Tabershaw IR and Thompson CS JOM 25 178-180 1983 Cooper WC Wong O Trent LS Harris F. An updated study of taconite miners and millers exposed to silica and asbestiform amphiboles J Occup Med 1992 1173-80 Davis JM Addison J Bolton RE Donaldson K Jones AD Smith T. The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection Br J Exp Pathol 1986 415-30 Delzell E Oestenstad K Honda Y Brill I Cole P. A follow study of mortality patterns among Gouverneur Tale Company workers Birmingham University of Alabama 20 Mar 1995 Capron S Fleury J Nebut M De Neef R JaurandMC Some in vivo and in vitro studies carried out with tale samples In NATO ASI Series G 21. Health Related Effects of Phyllosilicates J Bignon ed Berlin Springer 1990 Pp369-376 Gamble JF A nested case control study of lung cancer among New York tale workers Int Arch Occup Environ Health 1993,64 449- 56 Goodman JI An analysis of the National Toxicology Program's NTP Technical Report NTP TR 421 on the toxicology and carcinogenesis studies of falc Regul Toxicol Pharmacol 1995 244-9 International Agency for Research on Cancer Tale In Silica and Some Silicates IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans 42 185-224 1987 Kelse JW Thompson CS The regulatory and mineralogical definitions of asbestos and their impact on amphibole dust analysis Am Ind Hyg Assoc J. 50 613-22 1989 Kleinfeld M Messite J Kooyman O Zaki M. Mortality among tale miners and millers in New York State Arch Environ Health 14 663-7 1967 Kleinfeld M Messite J Zaki MH Mortality experiences among tale workers a follow study J Occup Med 1974 May 345-9 http 72 14 203 search vKzb3nEaXCsJ duk_nd Pneumoconiosis 6 of 4/12/2006 | 31 24 PM SATISTUL DE Uccupational & Environmental Medicine Kullman GJ Greife AL Costello J Hearl FJ Occupational exposures to fibers and quartz at 19 crushed stone mining and milling operations Am J Ind Med 1995 641-60 Kusiak R Springer J Richie A et al Carcinoma of the lung in Ontario gold miners possible aetiological factors Br J Industr Med 48 808-817 1991 Lamm SH Levine MS Starr JA Tirey SL Analysis of excess lung cancer risk in short employees Am J Epidemiol 1988 Jun.127 1202-9 Lippmann M. Asbestos exposure indices Environ Res 1988 86-106 McDonald JC Gibbs GW Liddell FD McDonald AD Mortality after long exposure to cummingtonite Am Rev Respir Dis 1978 271-7 National Institute for Occupational Safety and Heallth Technical Report Occupational Exposure to Tale Containing Asbestos DHEW NIOSH Publication No. 80-115 1980 National Institute for Occupational Safety and Heallth Health Hazard Report RT Vanderbilt Company HETA 90-390-2065 1990 National Toxicology Program Toxicology and Carcinogenesis Studies of Tale in F344 Rats and B6C3F1 Mice Technical Report Series No. 421 NIH Publ No. 93-315 Oberdorster G. Lung particle overload implications for occupational exposures to particles Regul Toxicol Pharmacol 1995a Feb 123-35 Oberdorster The NTP inhalation study a critical appraisal focused on lung particle overload Regul Toxicol Pharmacol 1995b 233-41 Oehlert GW A reanalysis of the Stanton et al pleural sarcoma data Environ Res 1991 Apr 194-205 Paoletti L Caiazza S Donelli G Pocchiari F. Evaluation by electron microscopy techniques of asbestos contamination in industrial cosmetic and pharmaceutical talcs Reg Toxicol Pharm 4 222-235 1984 Reger R Morgan WK On tale tremolite and tergiversation Br J Ind Med 1990 505-7 Rubino GF Scansetti G Piolatto et al Mortality study in tale miners and millers J Occup Med 18 187-193 1976 Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis Unit A survey of the longterm effects of tale and kaolin pleurodesis J Dis Chest 1979 285-8 Selevan SG Dement JM Wagoner JK Froines JR Mortality patterns among miners and millers of asbestiform talc preliminary report J Environ Pathol Toxicol 1979 273-84 Smith WE Hubert DD Sobel HJ Marquet E. Biologic tests of tremolite in hamsters Dusts and Disease Pathotox Publishers 1979 Pp 335-339 Stanton MF Layard M Tegeris A Miller E May M Morgan E Smith A. Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals J Natl Cancer Inst 1981 Nov http 72 14 203 search vKzb3nEaXCSJ duk_nd Pneumoconiosis 7 of 4/12/2006 | 31 24 PM DIVISION of Occupational & Environmental Medicine 965-75 Steenland K Brown D. Mortality study of gold miners exposed to silica and nonasbestiform amphibole minerals an update with 14 more years of follow Am J Ind Med 1995 217-29 Stenback F Rowland J. Role of talc and pyrene in respiratory tumor formation An experimental study Scand J Resp Dis 59 130-140 1978 Stille WT Tabershaw IR The mortality experience of upstate New York tale workers J Occup Med 1982 480-4 Thomas TL Lung cancer mortality among pottery workers in the United States IARC Sci Publ 75-81 Wergeland E Andersen A Baerheim A. Am J Ind Med 505-13 Wehner AP Zwicker GM Cannon WC Watson CR Carlton WW Inhalation of talc baby powder by hamsters Food Cosmetics Toxiocol 15 121-9 1977 Wylie AG Bailey KF Kelse JW Lee RJ The importance of width in asbestos fiber carcinogenicity and its implications for public policy Am Ind Hyg Assoc J 1993 239-52 Wylie AG Skinner HC Marsh J Snyder H Garzione C Hodkinson D Winters R Mossman BT Mineralogical features associated with cytotoxic and proliferative effects of fibrous tale and asbestos on rodent tracheal epithelial and pleural Mesothelial cells Toxicol Appl Pharmacol 1997 Nov 143-50 http.72 http.72 14 203 search vKzb3nEaXCSJ duk Pneumoconiosis 8 of 4/12/2006 1 31 24 PM