Document g9K1Xbk3w94N6xr2DDVdnx3V

It OSHA d o c k et o ffic er DATE k 1990 TIM E_______ distributed as another membership service by the \American Mining Congress HEALTH EFFECTS OF TREMOLITE This Official Statement Of The American Thoracic Society Was Adopted By The A TS Board of Directors, June, 1990 PLAINTIFFS EXHIBIT C A M -286 CAMC-Abeyta-002362 INTRODUCTION The risks of exposure to the major commercial asbestos fib er types encountered in mining and milling, m anufacturing, and product use are well known. T here is increasing consensus th at amphibole exposure (crocidolite and amosite) is more hazardous than exposure to chrysotile, p articu larly as it relates to mesothelioma risk . In addition, there has been u n certain ty in reg ard to w hether the chrysotile risk is a ttrib u ta b le to this fib e r, or to its common contaminant, trem olite, an amphibole fiber which has had little commercial u s e . In addition to chrysotile ore, tremolite contaminates deposits of talc and verm iculite. Some epidemiologic stu d ies of th ese in d u strie s have re p o rte d excess lung cancers and mesotheliomas, an appropriate cause for concern. Assessment of tremolite exposure risk has also been approached by animal studies and mineralogic analysis of human lungs. A troublesome issue has been the mineralogical distinction between fibers and cleavage fragm ents, and w hether this distinction has biological implications. Federal regulatory agencies have participated in the intense debate on tremolite issues. Tremolite -contaminate d play sand has been the subject of considerable deliberation by the Consumer P roduct Safety Commission. The Occupational Safety and Health Administration has had a long in te re st in how (and w hether) non-asbestiform amphiboles (including trem olite) should be regulated. The agency recently proposed revised standards for occupational exposure to asbestos which would omit non-asbestiform amphiboles (in cluding trem olite) from the rulemaking. The Scientific Assembly on Environm ental and Occupational Health of the American Thoracic Society appointed a Committee on Health Effects of Tremolite in 1988. Its charge was to critically assess the scientific knowledge concerning health risk s from tremolite e x p o su res. This re p o rt will ad d re ss the epidemiologic, animal, and mineralogical inform ation, and comment on some of the regulatory issues. A d raft rep o rt of the Committee was presented to the membership at the Annual Meeting of the ATS in May, 1989, in a public forum. Extensive discussion at that time and a substantial num ber of w ritten comments and other materials were provided to the Committee by a wide v ariety of interested persons and organizations in the months following the Annual Meeting. The Committee appreciates these re sp o n se s, has carefully considered all of the subm issions, and has made considerable revisions of the d raft re p o rt. h UG fc ' 3 0 1.: > P Pi ? c , P PI J C, C l , , 1 C r , - CAMC-Abeyta-002363 MINERALOGIC ISSUES As noted above, the focus on trem alite has raised the issue of the importance of cleavage fragm ents as opposed to asbestiform fib e rs. The issu e, fundam entally, is w hether two fibrous p articles of identical size and shape will have different biologic properties if the particles are pieces of mineral which have broken off a larger sample parallel to a cry stal face ( i . e . , cleavage fragm ents) as opposed to particles which have originally grown in a fibrous habit (i.e ., asbestiform fibers). - It became apparent both from our review of the literatu re and from submissions made to th is Committee b y experienced m ineralogists, th at the distinction between cleavage fragm ents and asbestiform fib ers, although theoretically clear, is in practice extrem ely m urky. Some m ineralogists believe th at these two types of particles are always d istin ct, whereas others believe they shade off one into the other, and th at interm ediate forms (byssolite) exist. F urther, these same submissions were at odds with each other in identifying particular samples used in various experim ents (including the play sand samples analyzed by members of the Committee) as asbestiform fib ers or cleavage fragm ents. To complicate m atters, it was also suggested to us that th e important distinction is not th at between cleavage fragm ents and asbestiform fibers, but between non- asbestiform and asbestiform fibers. Because of the lack of consensus among m ineralogists, as well as the limited information about the minerals p re se n t in most published human and animal data ( i .e ., w hether the particles used or observed really are fibers or cleavage fra g m e n ts), we have to a g reat extent ignored the distinction, and ended up tre a tin g most of the data as based on 11fibers" of various sizes. The Committee recognizes that this is not an ideal solution, and where stronger evidence for the cleavage fragm ent or asbestiform n a tu re of a p articu la r fiber e x ists, we have noted it. However, until th e re is reasonable mineralogic unanim ity both on general definition and the classification of specific samples, and then animal experim entation with such classified m aterials, it appears to us impossible to draw general conclusions about biologic effects based on the distinction between cleavage fragm ents and asbestiform fibers. EPIDEMIOLOGIC EVIDENCE Epidemiologic information concerning tremolite as a potential health risk comes from studies of w orkers occupationally exposed as a consequence of tremolitic contamination of ores (ch ry so tile, verm iculite and ta lc ), and of resid en ts of certain regions in T urkey where exposures resu lt from naturally-occurring deposits. 3 CAMC-Abeyta-002364 Chrysotile There is stro n g epidemiologic evidence th at the amphiboles amosite and -- crocidolite are considerably more dangerous than chrysotile in causing mesothelioma ( 1 ) . Because of th is, and because most chrysotile deposits also contain th e amphibole trem olite, it is possible th a t th e rela tiv e ly few mesothelioma cases among chrysotile w orkers may actually have been caused by tremolite a sb e sto s. S upporting evidence fo r the role of trem olite comes prim arily from mineralogie analyses of lu n g s, which have found th at the most important difference between mesothelioma cases and matched controls is the amphibole content, including tremolite (2 a ,Z b ). It should be understood that mineralogie analyses of the lungs have been used as an indicator of exposure, because the tremolite usually constitutes only a very small and variable fraction of the chrysotile o re, and therefore m easurem ents of tremolite exposure levels for th ese ch ry so tile w orkers do not exist. Vermiculite Workers from two vermiculite mines have been studied: one in Libby, Montana, studied b y two independent groups of research ers (3 - 6 ), and one in South Carolina ( 7 ) . Ores from both mines are reported to have been contaminated with trem olite asbestos (and non-asbestiform trem olite) but fib er exposure levels were lower in South Carolina. However, some u n c ertain ty regarding tremolite asbestos contamination at the Libby mine has been expressed (2o ltai, Tibor: P ersonal communication to th e Committee, citin g B ates, R .L ., Geology of the Industrial Rocks and M inerals, H arper and B rothers, 1960). By contrast, a member of th is Committee (P . S ebastien) was involved in th e mineralogical evaluation of the Libby mine, and is convinced th a t the deposits contain "true asbestiform fibers". The Libby cohort included w orkers employed for at least a year. Exposure estim ates (in fibers p e r ml) were based on m easurem ents in the 1970's using the membrane filter method, and on tren d s in m easurements made in the past using the midget impinger method. In this cohort, with a mean length of employment of 8 .7 y e a rs , th ere were excess pneumoconioses (e ig h t c a s e s ), four cases of mesothelioma, and an excess lung cancer risk [tw enty or more years from hire: 15 o b se rv e d , 5 .3 expected, fo r a Standardized M ortality Ratio (SMR) of 2 .8 5 ] ( 3 ) . T hough there was considerable v ariab ility in th e SMR's, the lung cancer risk was significantly related to estim ated cumulative exposure. Because of the non-fibrous n a tu re of verm iculite, and the fin d in g of pneumoconioses and elevated lung cancer, tremolite was in terp reted to be the causative a g e n t. A dditionally, the m orbidity stu d ies ( 4 , 6 ) found evidence of fib rotie e ffe c ts , including parenchym al small o p a citie s, pleural thickening and pleural calcification. h U>3 6 ' 3 0 ] : 14 4 fi P fi C ' . i r r> r* e CAMC-Abeyta-002365 Taken together the findings for this cohort indicate th at tremolite asbestos exposures resu lt in re s p ira to ry health consequences similar to other forms of asbestos, including lung cancer and mesothelioma. Among the smaller cohort (1 9 4 ) o fS o u th Car ol i na verm icuhte miners employed for at l i s t a months, thara w er. four t a * cancer daatha. varans 3.3 expected, and no mesothelioma or pneumoconioses cases SJ). U s in g the dose response relationship fo r Montana, the authors calculated that a detectable increase in lung cancer ris k would not have been expected because c f the low exposure levels and the small size of the cohort. 'T he resu lts therefore do not add information: they are consistent with both the Libby results and a conclusion of no attrib u tab le health risk . The observation for th e Libby cohort of a dose-response relationship for lung c a n c e r ^ k 5 important evidence of tremolite asbestos as a carcinogen m vermiculite mining. However, since this is based on only one cohort, data on other relatively larg e populations of verm iculite miners are available, fhe a ^ w S t o a u S ? in S e c r e t i n g non-replicated epidemiologic study r e s ^ u i w T r i n t e d , an approach also suggested by the indicated reservations regarding the mineralogy of the Libby deposit. Talc Two cohorts of New York State talc miners have been stu d ied for evidence of health risks. One group, 260 w orkers employed at least fifteen y e ars in several New York m inesw ith asbestiform trem olite contamination (8 , 9 ) , was the subject of a crooortionsd m ortality s tu d y . Of all 108 d eath s, 27% were due to pneumoconiosis, and there was one peritoneal mesothelioma; however, since talc San cause lung fibrosis, and information concerning other exposures of workers was ^ a v a i l a b l e , these deaths cannot be attrib u ted to tremolite exposure. An excess in lung cancer risk was noted: the th irteen lung can cercases constituted 12% of all d e a th s, compared with an expected 3.7% ^ se^ n^ 55 U .S. ra te s. Risk did not exhibit a relationship with duration of employment. A firm conclusion of an elevated lu n g cancer risk cannot be made from this stu d y for a number of re a so n s, including the lack of a dose-response relationship, the potential problems of all proportional m ortality stu d ies, the fact that New York lu n g cancer rate s d u rin g 1950-1959 were higher than U .S . rates (b y 29%), and the lack of smoking information. Employees of a New York talc mine were the subjects of th ree published p ap ers and an unpublished rep o rt b y the National Institute for Occupational Safety and Health INIOSH) (1 0 ). Brown, et a l . , (1 1 ) reported th a t ore samples were found to contain asbestiform m inerals, including trem olite, and to b e similar to that from other New York m ines. T here h a s, how ever, been dispute reg ard in g the mineralogic compositon of th ese talc deposits (Viylie: Personal communication to the Committee). 5 CAMC-Abeyta-002366 The first of th e stu d ies (1 1 ) included 398 men hired d u rin g 1947-1959 ; the second (1 2 ), 655 men hired during 194B-1977; the th ird was prim arily a reanalysis of th e Stille and Tabershaw data (1 3 ). All th re e had im portant limitations in th e ir data analyses: the firs t considered follow-up time since h ire, but not any indicator of exposure, though job records were available; the second separately analyzed w orkers with and without previous employment elsewhere, b u t did not consider follow-up period or exposure indicators; the third considered duration of employment and previous employment elsew here, but did not control for follow-up time. - NIOSH in v estig ato rs recently expanded the cohort to men h ired d u rin g 1947 1978, continued follow-up of the cohort through 1983, considered both follow-up period and le n g th of employment, and included a n ested case-control stu d y of all confirmed lu n g cancer cases (1 0 ). The re su lts of th is la te st re p o rt will be reviewed h ere, since it contains the most recent data and complete analyses. Twenty or more years after hire (which includes thirteen of the seventeen lung cancer cases occurring through 1983), the only significantly elevated lung cancer risk was observed among workers employed less than one year (8 observed, 2.24 ex p ected , SMR = 35 7.2, one-tailed p < .0 1 ). By c o n tra st, among those employed at least one year, the risk was not significantly elevated (5/2.81, one-tailed p > .1 5 ), and there was not a trend of risk with duration employed (fo r d u ratio n s of 1 -9 , 10-19 and > 20 y e a rs, th e SMB's were 82 [1 / 1 .2 ], 446 [2 / 0 .5 ], and 176 [2 / 1 .1 ], resp ectiv ely ). This finding of an elevated risk restricted prim arily to sh o rt-term w orkers is consistent with several epidemiologic studies of oth er exposures; it has been noted that sh o rt-term workers are particularly difficult to evaluate and may differ from o th er w orkers in ways related to cancer risk , possibly including personal lifestyles (1 4 ). The nested ease-control stu d y of all tw enty-tw o lung cancer cases (including five which occurred a fte r 1983), each matched with th ree controls, was able to evaluate the potential role of smoking and other occupational ex posures. Smoking was found to be a significant facto r, b u t th ere was no evidence of an effect of o th er occupational exposure or length of employ- ment at the mine; in fact, there was a generally decreasing risk with duration of mine employment. The results of the case-control study and the lack of any dose-response relationship for lung cancer risk in the cohort study do not support a conclusion th a t the elevated ris k in this population was a ttrib u ta b le to mine exposures. NIOSH also conducted a stu d y of 392 miners who had w orked fo r at least a year in Vermont talc mines, in which the ore was reported to be free of asbestos contamination (1 5 ). Miners were found to have had excess lung cancer risk (5/1.15 = 4 .3 5 , p < .0 1 ), though millers did not (2 /1 .9 6 = 1 .0 2 ), even though millers were believed to have had higher exposure lev els. Risk was not evaluated in relation to any other indicator of exposure. The authors mentioned . 6 ftU-6 6 ' 50 16 : 15 CAMC-Abeyta-002367 several potential influencing factors for which no information was available, including radon exposure, smoking, and previous work in a local talc mine'with tremolite contamination. These results do not demonstrate an exposure-related lung cancer risk. A study of a large cohort (n * 2,,000) of Italian talc miners (1 6 ) employed at least one y ear found no evidence of excess cancer risk. The ore is reputed to be one of the p u rest anyw here, although analyses of the ore found a small amount of trem olite. An observed pneumoconiosis risk was a ttrib u te d b y the authors to silica exposure. A National Cancer Institute (NCI) stu d y of workers in three ceramic m anufacturing plants (17) categorized w orkers with high silica dust exposure into three categories of talc exposure: none, fibrous (trem olitic) talc, and non fibrous talc, stated to contain no asb esto s. There was not a significantly elevated lung cancer risk among either the non-talc (18/13.2= 1.37) or the fibrous talc workers (5/2.9= 1.74), but the non-fibrous talc group had a significantly elevated lung cancer risk (21/8.3= 2.54, p < .001) which exhibited a trend with duration of employment in non-fibrous talc jobs. There are a number of methodologic problems with this stu d y , including the lack of smoking inform ation, the relatively small num ber of fibrous talc w o rk ers, and the use of u .S . ra th e r than local m ortality r a t e s . However, as rep o rted , these resu lts do not support a carcinogenic role of trem olite, since the tremolitic talc appeared to be less hazardous than the asbestos-free talc. In summary, none of the talc studies has convincingly demonstrated an increased lung cancer risk reliably attrib u ted to exposure, and the v ery similar re s u lts fo r New York and Vermont mine w o rk ers, whose tremolite exposures were apparently different, do not su p p o rt a role for tremolite as a lung carcinogen in talc mining (w hether the tremolite was asbestiform or n o t). Environmental Exposures in T urkey Elevated mesothelioma risk has been observed among inhabitants of ru ral areas in T urkey with naturally occurring asbestiform tremolite (1 8 ). While th ere is no occupational asbestos exposure in the a re a, some residents have apparently had very high tremolite exposures as a consequence of numerous natural outcrops, and the use of the mineral dust in whitewash and stucco for houses. atients with pleural plaques and diffuse thickening, and diffuse pulmonary fibrosis, have also been reported. The lack of evidence of any other fiber exposure strongly suggests tremolite asbestos as the cause. Finally -- while not tremolite -- sh o rt, non-asbestiform amphibole exposures (cum nungtonite-grunerite) have occurred in two populations wh_.h have been studied for mortality experience. Both the Homestake and Reserve Mining studies failed to show either an overall excess lung cancer risk , or a gradient M(. JaySy^Zn\Jh) Hsk With increasinK estimated past ------ exposures within the cohorts. 7~ CAMC-Abeyta-002368 Summary of the Epidemiologic Evidence In summarizing th e limited, epidemiologic data on trem olite e x p o su re, the Montana verm iculite w orkers demonstrated a mesothelioma risk and an excess lung cancer risk , which is dose-related and fu rth er strengthens the conclusion that tremolite asbestos should be considered to be carcinogenic, and should be regulated accordingly. The dose-response relationship based on the Montana experience can be used to establish allowable occupational and environmental exposure levels for asbestiform trem olite. Additional su p p o rt for a role of tremolite asbestos as a human carcinogen comes from the lung b u rd en analyses of Quebec chrysotile miners (see following sectio n ). However, talc workers have not been convincingly demonstrated to have an exposure-related cancer risk , and there is continuing controversy as to w hether the relevant talc deposits contained asbestiform trem olite.. LUNG BURDEN STUDIES OF TREMOLITE Relatively little information is available on the tremolite content of human lung in occupationally or environmentally exposed populations, or on the fibers to which various populations have been exposed, b u t the data which do exist indicate th at both fiber concentration and fiber size can be correlated with disease p attern s. It should be noted th a t mineral analysis of fiber content in the lungs of these workers does p re s e n t some problem s. For one th in g , chrysotile tends to disappear rap id ly from lu n g , so th a t the typical lung of a chrysotile miner will contain more tremolite than chrysotile, even though trem olite constitutes only a few p ercent of th e ore. Secondly, different research groups have chosen to count fib e rs of d iffe re n t minimal lengths in th e ir analyses; th ere are valid reasons for each approach, b u t the results are not always -comparable, as noted below. In the lungs of Quebec and Cypriot chrysotile miners, tremolite is the predom inant residual fib e r, even though it constitutes only a few percent of the original ore (2 1 ,2 2 ). Chrysotile-derived tremolite is also seen in substantial amounts in the lungs of South Carolina textile w orkers, albeit in a lesser ratio to chrysotile (2 3 -2 5 ). In the Quebec mining and milling population, the concentration of tremolite in workers with asbestosis is, overall, markedly increased compared to those with no parenchymal disease (2 6 ). In both the Quebec mining and milling population, and the South Carolina textile w orkers, there is a good correlation between the concentration of tremolite p er gram of lung tissue and the degree of in terstitial fibrosis (asb esto sis) (2 3 ,2 7 ); th ere is also, however, a reasonably strong correlation between chrysotile concentration and severity of fibrosis (2 3 ,2 7 ), and the present data c . not indicate w hether tremolite or chrysotile is more important in this p ro c e s s . Compared to the incidence in workers heavily exposed to amosite or crocidolite, mesotheliomas are relatively scarce in the Quebec chrysotile mining population. Although analysis shows that occasional cases from the mining regions have amosite and crocidolite in th e ir lungs (p a rtic u la rly w orkers from the region of the town of A sbestos [ 2 8 ] ) , most of the 8 h U'3 6 ' 9 0 l B : 1 7 Pi P c. o c-n a r r* - r CAMC-Abeyta-002369 cases, and especially those from the region of T hetford mines, contain only tremolite and chrysotile (th e former in larger amounts than the latter [2 9 ,3 0 ]), indicating th at one or both of these fibers is the agent inducing mesothelioma. It is notew orthy that the median tremolite content of the lungs of the Quebec w orkers with mesothelioma is Bomewhat above th a t of those with asbestosis (2 ) . This is in d irect c o n tra st to the situation in w orkers w ith heavy exposure to amosite or crocidolite, where mesothelioma appears at fa r lower lung burdens than asbestosis (2 ). If one counts all fib ers, then the tremolite found in the lungs of Quebec chrysotile w orkers ap p ears to be a relatively s h o rt, low aspect ratio fiber (geometric mean length 2 microns, geometric mean aspect ratio 8:1-10:1), p a rticu la rly when compared to the amosite and crocidolite found in the lungs of shipyard w orkers or insulators (2 6 ). If one counts only fibers longer than 5 m icrons, as does the g roup at McGill, then in fact the geometric mean aspect ratio of tremolite fibers is measured at greater than 20:1 (3 0 ). Tremolite exposure from ambient air has been documented by lung analysis in various environm entally-exposed populations. Tremolite, like other amphibales, appears to accumulate read ily in lungs at all exposure levels, and is the most commonly encountered amphibole fiber in the lungs of u rb a n dwellers in North America (2 1 ). Here again, the fib er ia a sh o rt, low -aspect ratio mineral (actually considerably sh o rte r than the fibers seen in chrysotile m iners), which is probably derived from chrysotile ore (2 1 ). Of particxilar in te re st is the lu n g burden of the re sid e n ts of the Quebec mining townships of Asbestos (2 8 ) and Thetford Mines/Black Lak e (28,31 -3 3). Analysis of lung asbestos content in the latter shows th at these lungs contain approximately as much tremolite as chrysotile (2 8 ,3 1 -3 3 ), even though the ambient chrysotile level is several hundred-fold higher than the ambient tremolite level (3 4 ), In re sid en ts of A sbestos, how ever, th ere is no tremolite excess, presum ably because the ambient tremolite concentration (0.0002 fib e rs/c c ) is much less than in T hetford Mines (0 .0 0 1 5 fib e rs/c c ) (3 4 ). Studies from two d ifferen t laboratories have confirmed th a t the population of T hetford Mines who have n e v e r been employed in the asbestos industry carry a higher trem olite, as well as chrysotile, burden compared to residents of North American u rb an areas (2 8 ,3 1 - 3 3 ). The McGill group stu d ies have also recently shown th a t this lung b u rd en is significantly correlated both with distance of domicile from the mines, and with time lived in the mining region (3 2 ,3 3 ). Even g re a te r b u rd en s are found in those who have household contact exposure because a close relative works in the mining and milling in d u stry (3 2 ). Although this burden is apparently occasionally associated with pleural plaques (plaques were seen in seven of seventy-two cases studied by Case, et al. [2 8 ,3 0 ]), particu larly in individuals such as farm ers who encounter dust from soil (3 5 ), there is no epidemiologic evidence th a t eith er chrysotile or tremolite at this level produces an excess of lung cancer or mesothelioma. 9 CAMC-Abeyta-002370 By c o n tra st, stu d ies of lung content of populations environm entally exposed to " longer, and usually much higher aspect ratio, tremlate indicate that this type of fiber is a potent mesothelial carcinogen. Yaziogliu, et a l . , (3 6 ) reported a population in T urkey, and Constantopoulos, et a l., (1 7 ,1 8 ) a population in G reece, with substantial incidences of mesothelioma and exposure to long fibers with aspect ratio g reater than 50. It has also been suggested th at long trem olite fib ers are responsible fo r some of the mesotheliomas seen in p e rso n s o th er th an chrysotile m iners in N orth America ( 2 b , 3 9 ). The exact role of length versus aspect ratio is uncertain, since several apparently environm entally-induced mesotheliomas have been rep o rted from an area of Corsica, where analysis of lung content indicates that the tremolite fibers are fairly long (probably on average as long as the amosite fibers seen in the lungs of shipyard and insulation w orkers in North A m erica), bu t the aspect ratio is lower (considerably lower th an is found for amosite or crocidolite) (4 0 ). The evidence on mineral lung burden implies th at long, high aspect ratio, tremolite fibers behave much like other amphiboles of comparable size, and are particularly dangerous because of their propensity to induce mesothelioma. The data appear to indicate th a t fa irly low aspect ratio fib e rs of trem olite are capable of causing d ise ase , pro b ab ly in fairly low concentrations in th e case of pleural plaques, b u t certainly only in v ery high concentrations in reg a rd to mesothelioma and asbestosis. However, this statem ent is made with considerable caution, because the populations with exposure to this type of mineral have also had extrem ely high chrysotile ex p o su re, an exposure w hich, as noted above, is not well reflected in mineral analyses of lung content; the role of chrysotile versus tremolite in producing disease in these patients cannot be clearly sorted out. ANIMAL STUDIES Only a nwQi num ber of animal studies have u sed trem olite, and these stu d ies are confounded b y difficulties in definition of the exact mineral used (p a rtic u la rly its size, len g th and s h a p e ), and in some in stan ces b y flawed experimental design or poor survival of anim als. Much of the in te rest in trem olite arose from the fact th a t it contaminates talc (4 1 ). Smith, et a l., (4 2 -4 5 ) found th at a commercial New York talc sample containing fifty p ercen t v e ry large diam eter trem olite (1 micron mean diam eter) produced no tumors when injected into the pleural cavity of ham sters. However, mesotheliomas were produced with what are described as long and thin or asbestiform fibers from other samples of tremolitic talc. U nfortunately, no details of the exact fiber sizes are provided, and it is impossible to determine w hether these samples would be p roperly classified as asbestiform or not. * The most im portant and w idely cited studies in re g a rd to trem olite are those by Stanton and colleagues (4 6 -4 9 ). Using a large number of different types of mineral fibers implanted directly into ra t pleural cavities, they showed that fiber carcinogenesis was related to fiber size, shape, and durability, ra th e r than to chemical composition p e r se. Although Stanton, 10 (hU 6 6 ' 9 0 1 6 : 1 5 >T' --v-o m .. c n ,t c r. >i CAMC-Abeyta-002371 et a l . , found th at fib er6 longer than 8 microns and narrow er than 0.25 microns in diameter w ere, in general, the most carcinogenic, they did observe a very high incidence of tum ors with trem olite, which in fact was much sh o rte r and... b ro ad e r. T heir data indicate th at tremoilite fib er populations in which the majority of the fib ers are g reater than 4j microns in length and have a diameter of less th an 1 .5 m icrons were among the most carcinogenic (100% tumor p r o b a b i l i t y ) of all th e differen t ty p es of m inerals te ste d when u sin g the intrapleural injection model. Wagner, et a l., (5 0 ) tested three samples of trem olite. A sample prepared from a South Korean rock which was about eighty percent fib ro u s, with about one-third of the fibers longer than 8 microns and most less than 0.6 microns in diam eter, produced mesotheliomas in th irty percent of animals. By contrast, two o th er samples which had few fib ers failed to produce any tum ors. The same gro u p also studied these fib ers in v itro , and the Korean fiber showed the greatest cytotoxic effects as measured by LDH, beta-glucuronidase release and giant cell formation. Davis, et a l . , (5 1 ) tested an asbestiform Korean tremolite in an inhalation experim ent, and found two mesotheliomas and sixteen carcinomas in forty animals. No tum ors were seen in the controls. Inspection of th eir data indicates that approximately sixty percent of the fibers were shorter than 4 microns and th ick er th an 0.25 m icrons, and n in ety percent had diameters of less than 1 micron. The authors noted th a t the tremolite was one of the most carcinogenic materials they had used. Davis, et a l . , are continuing experim ents with tremolite (communication to the committee). Preliminary analysis of their data indicates that asbestiform varieties of tremolite are highly carcinogenic and produce over ninety percent incidence of mesothelioma by eighteen m onths; it should be noted that the mean aspect ratio of these fibers was approxim ately 8:1. Of particu lar in te rest is the fact th at two samples which Davis describes as containing elongated spicules ra th e r th an tru e asbestiform fibers (an d described by A. G. Wylie in a submission to this Committee as b y sso lite) produced tumors in sixty-nine percent and twelve percent of animals. As well, a sample of tremolite containing many particles with an aspect ratio greater than 3:1, but described by Davis as "prismatic'' rath er than asbestiform , produced mesotheliomas in six percent of animals. Davis makes the point th at it is difficult to determine whether size and shape are the most im portant determinants of carcinogenicity in these experim ents, because the num bers of fibers injected vary greatly amongst the different samples, and there is a close correlation between fiber shape and fib er num ber in these p rep aratio n s; th u s, the most carcinogenic samples had both the highest total num ber of fibers and the greatest number longer than 5, 10, or 20 microns in lemgth. It should be noted th a t many of- th e original studies of-chrysotile toxicity by inhalation may have been influenced by the presence of tremolite. Wagner (52) noted th a t, although no tremolite was found in the original chrysotile fiber samples and fibers taken from the d u stin g cham bers using UICC chrysotile A and a fine Quebec chrysotile, on reanalysis of the lung burdens of exposed rats clearly indicated the presence of the fib er. Langer (5 3 ) was also 11 CAMC-Abeyta-002372 gamas-svas^ssrs?-st^iiea 'of^ ofSb o t h ^ n ^ ^ T d ChrySOtile' eve" though effects ascribed in animal studies to c w T ^ trem ohte, and to what extent unclear (5 2 ,5 5 ,5 6 ). ^ t0 eh*y*otile are really effects of tr S S S te is Review of the animal investigation e j . ... specifically exam iningth * ,althoug`h th e re are few such S d" Mf mestheliomas and carcinomas in ^*eTM o lite 11 is clear th a t trem olite powerful mesothelial carcinogen in 13? exPenm ental animals, and th a t it ic Q Stte^ cta diff*eretnecet hseo"f Stremolite clesv.TM iniorm inTrhe*graerdi toTMbioBloPgpicVaal r^T trem olite, but it is w orth noting th at^t-n S ?^?1611* comP a re d to asbestiform arnmals when exposure h L ? b 5 2 i does W * 1to be r c i n o ^ n i c in su b stan tial proportion of relatively ch^ J of P articles which includes a S worlc is needed to determ ine if tiuF eoncenf11'f b1r ad flb e r * C onsiderably more ferent from asbestiform fragm ents is valid Cleava* e fragm ents as biologically 3 6 ' 90 1 6 : 2 0 12 CAMC-Abeyta-002373 OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION In June 1986, the Occupational Safety and Health Administration (OSHA) promulgated revised standards fo r occupational exposure to asbestos in general industry and in construction. In both of these revised stan d ard s, asbestos is defined to include chrysotile, amosite, crocidolite, actinolite asbestos , tremolite asbestos, and anthophyllite asbestos. The revised standards recognize that actinolite, tremolite, and anthophyllite occur in both asbestiform and nonasbestiform habits. While OSHA recognized the occurrence of mineralogically distinct non-asbestiform habits for these three m inerals, the language of the new standards clearly indicated th at exposure to these minerals in their nonasbestiforin habits will be reg u lated in the same way as exposure to "tru e asb esto s". The re su ltin g controversy caused a delay in the implementation of the relevant portions of th e revised asbestos stan d ard s (a sta y of the new regulation as it pertains to non-asbestiform tremolite, anthophyllite and actinolite was extended to November, 1990). Historically, exposure to the minerals considered to be asbestos b y OSHA is determined by the number of fibers > 5 microns in length counted per cubic centimeter of air in a workplace using optical (phase contrast) microscopy. A > 3:1 length to diam eter, or asp ect, ratio is used b y OSHA to distinguish a fiber from other particles in a filtered sample of workplace a ir. The use of this specific aspect ratio is empiric (although su p p o rted b y both ACGIH and NIOSH), and is not a universally accepted mineralogical criterion. Mineralogists consider mineral fibers as crystalline units th at appear to have grown individually in an elongated shape resembling that of organic fibers (5 7 ). So-called "cleavage fragm ents" can be produced b y breakage of crystals parallel to their faces (5 7 ,5 8 ). Cleavage fragm ents of minerals like actinolite, tremolite, and anthophyllite may resem ble organic fib e rs, and may meet the OSHA definitions of a fiber ( i . e . , are > 5 microns in length and have a > 3:1 aspect ratio ). Such cleavage fragments are described b y terms such as elongated, acicular, and fibrous, bu t are not considered tru e asbestos fibers by many mineralogists (5 7 -5 9 ). The term "asbestiform " has not been previously defined for regulatory purposes. OSHA considers asbestiform fib ers to be "crystals th at grow naturally as long, flexible, durable f i b e r s . . These fib ers are found in bundles that can be easily separated into smaller fibers or fib rils, and during processing still maintain th eir same surface p ro p erties and a ctiv itie s. Campbell and others have proposed definitional criteria for asbestiform particulates that are much more exclusive than the c u rre n t OSHA regulatory language (5 8 ,5 9 ). They would re stric t the term asbesiform to include only those particles > 5 microns in le n g th , <5 microns in diam eter, with a > 20:1 aspect ra tio , and with two or more of the following population c h a ra c te ristic s: parallel fibers occurring in bundles; fib er bundles with splayed ends; fib ers in the form of thin needles; knotted masses of in ividual f ib e rs ; and fibers showing c u rv a tu re . A notice of proposed supplem ental rulemaking was published in the Federal Register on F eb ru ary 12, 1990. In it, OSHA proposes to lift the adm inistrative stay and amend the revised asbestos standards to remove non-asbestiform 13 CAMC-Abeyta-002374 tremolite, anthophyllite and actinolite from their scope, L e . , not regulate these m inerals in the same way as a sb e sto s. In discussing the raineralogic issu e s, OSHA p oints out th at w hether o r not these minerals are "asbestiform " depends" not on th eir crystalline stru c tu re , but ra th e r on the manner of crystal growth or the mineral habit. They agree th at "There is mineralogic terminology which identifies, as a gross level, distinct and different mineral habits. However at the m icroscopic level, for small d iscrete p a rtic le s, such as those collected on air monitoring filters, these distinctions become leas clear." In discussing the health effects data, the agency points out that it has generally not been possible to clearly distinguish between exposures to asbestiform and nonasbestiform mineral -- both were most often likely to have been in the exposure mix. The agency invited public comment on this proposed action, and alternative regulatory approaches. It seemd clear, from its discussion of the mineralogic and biologic effect is s u e s , th a t OSHA is fa r from convinced th a t c u rre n t scientific knowledge supports its proposed rulem aking. They do concede, how ever, th at human and animal data are not "sufficiently supportive" to conclude th at the risks are similar in "type and magnitude" for both asbestiform and non-asbestiform minerals. Review of several critiques (6 0 ,6 1 ) of the human and animal studies that provide much of the data base for assessing the toxicity of the non-commercial amphiboles prom pts concern over how well the mineralogical definition of what constitutes "true asbestos fibers" can be quantified for regulatory purposes. Often in th ese critiques, the emphasis is prim arily on p recise mineralogical terminology rath e r than biological effect. If the m echanism (s) of asbestosinduced or promoted carcinogenesis were clearly understood , in both mineralogical and biological term s, then we could proceed easily to distinguish what is tru ly asbestiform and non-asbestiform for regulatory purposes. However, since such clarity of understanding is not ap p aren t, it would seem prudent public health policy to use an inclusive, ra th e r than an exclusive, definition of asb esto s. The prim ary issue is not so much what is or is not an asbestos fiber in mineralogical terms; ra th e r, it is what particle dimensions are carcinogenic and what are not. A secondary issue is w hether particle surface characteristics are important in predicting carcinogenic potential. 14 CAMC-Abeyta-002375 CONCLUSIONS 1. Unquestioned health effects of tremolite asbestos have been demonstrated in both man and anim als. These effects a re identical to those produced by o th e r forms of a sb e s to s. 2. T here may be im portant physico-chem ical distinctions betw een asbastiform and non-asbestiform tremolite dust particles. However, there appears to be considerable controversy in applying these mineraloga definitions to specific samples of m ineral, particularly individual particles viewed microscopically after collection by air sampling or found in human lung, or when used experimentally. . 3. The evidence for biological effect distinctions based on mineralogical param eters, other than fib er dimension and fiber number, is currently inadequate. 4. At p resen t, the prudent public health policy course is to regard ap p ropriately sized trem olite ''fib e rs" , in sufficient exposure dose (concentration and d u ratio n ), as capable of producing the recognized . asbestos-related diseases, and they should be regulated accordingly. 5. Although recognizing the practical problems involved, there should be fu rth e r research on the possible biological implications of any widely accepted mineralogical distinctions, and on whether the "regulatory fiber" definition -- aspect ratio >3:1, >5 microns in length -- should be modified to b e tte r reflect biological effect information. 15 CAMC-Abeyta-002376 - REFERENCES 1. Vieill H, Hughes JM. A sbestos health effects: resolving the scientific u n c ertain tie s. P ostgrad Med J 1988; 64:48-55. 2a. C hurg A, Wright JL. F iber content of lung in amphibole vs chryaotile-induced mesothelioma. In, Non-occupational exposure to mineral fib ers. Edited by J Bignon, et a l . , Lyon: lARC; 1989. Pages 314-318. 2b. McDonald JC , A rm strong B , Case B, Doell D, McCaughey WTE, McDonald AD, Sebastien P. Mesothelioma and asbestos fib er ty p e . Evidence from lung tissue analyses. Cancer 1989; 63:1544-1547. 3. McDonald JC, McDonald AD, A rm strong B , Sebastien P . 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Kleinfeld M, Messite J , Zaki MH. M ortality experiences among talc w orkers: a follow-up stu d y . J Occup Med 1974; 16:345-349. 10. Gamble J , Piacitelli G. R eport to R. T. V anderbilt Company, In c ./ Governeur Talc Company, April, 1988 (u n p u b lish ed ). 11. Brown DP, Dement JM, Wagoner JK. M ortality p a tte rn s among miners and millers occupationally exposed to asbestiform talc. In: Lernen R, Dement JM ( e d s ), Dust and Disease: Proceedings of the Conference on Occupational Exposures to Fibrous and Particulate Dust and Their Extension Into the Environment, 1977, W ashington, D.C. Park Forest South, Illinois: Pathotox Publishers, Inc., 1979; 317-324. 16 CAMC-Abeyta-002377 1 2 . Stille WT, T abershaw 1R. The mortality experience of u p sta te New York talc w orkers. J Occup Med 1982; 24:480-484. * 13. Lamm SH, Levine MS, S ta rr JA, Tirey SL. Analysis of excess lune cancer risk m sh o rt-term employees. Am J Epid 1988; 127( 6) : 1202-1209. 14. 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M c D o n al de t al. Mortality after long exposure to cummingtoniteg ru n e n te . Am Rev R espir Dis 1978; 118:271-277. 20. Higgins ITT, Glassman JH, Oh MS, Cornell RG. M ortality of reserv e rtpTid f19Q8o3?;m31^ 1o8y:7,,e1m0-p7l1o9y.ees in reiaticm t0 talconite d u st exposure. Am J 21. C hurg A, Wiggs B. Fiber size and num ber in w orkers exposed to processed chrysotile asbeBtos, chrysotile miners, and the general population. Am J Ind Med 1986; 9:143-152. 22. McConnochie K, Simonato L, Mavrides P, Chrisofides P, Pooley FD 42*1^2-347' Mesothelioma in Cyprus: the role of trem olite. Thorax 1987 ; p S S n I S J f ^ arley * !, Vai1y athan v > Dement J, Pooley F, Althouse R. H trosis and asbestos exposure in chrysotile asbestos textile r k e r s . preliminary resu lts. Accomplishments Oncol 1986; 1:59-68. 17 CAMC-Abeyta-002378 24. Pooley FD, Mitha R. Fiber types, concentrations, and characteristics found in lung tissu es of chrysotile-exposed cases and controls. 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Lung asbestos content in long-term residents of a chrysotile mining town. Am Rev R espir Dis 1986; 134:125-127. 32. Case B. Microanalytic classification of environm ental exposure in a chrysotile mining region. Am Rev R esp ir Dis 1988; 137 (P a rt 2):A94. 33. Case BW, Sebastien P . F iber levels in lu n g and correlation with air samples. Increased intrapulm onary fiber levels. In, Non-occupational expostxre to mineral fib e rs. Edited b y J B ignon, et al. Lyon: 1ARC; 1989. Pages 34. Sebastien P , Plourde M, Robb R, et al. Ambient a ir asbestos su rv e y in Quebec mining tow ns. P a rt 2--Main s tu d y . Environm ent Canada R eport 5/AP/RQ-2E, 1986. 35. Churg A, DePaoli L. Environmental pleural plaques in residents of a Quebec chrysotile mining town. Chest 1988; 94:58-60. 36. Yazicioglu S, Ilcayto R, Balci K, Sayli BS, Yorulmaz B. Pleural calcifications, pleural mesotheliomas, and bronchial cancers caused by tremolite du st. Thorax 1980; 35:564-569. 18 CAMC-Abeyta-002379 37. L anger AM, Nolan RP, Constantopoulos SH, Moutsopoulos HM. Association of Metsovo lu n g and pleural mesothelioma with exposure to tremolite-containing whitewash. Lancet 1987; 1:985-967. 38. Constantopoulos SH, Goudevenos JA, Saratzi N, L anger AM, Selikoff IJ , Moutsopoulos HM. Metsovo lung: pleural calcification and re stric tiv e lung function in N orthw estern Greece. Environmental exposure to mineral fiber as etiology. Environ Res 1985; 38:319-331. 39. McDonald JC. Trem olite, oth er amphiboles, and mesothelioma. Am J Ind Med 1988; 14:247-249. 40. Magee F, Wright JL, Chan N, Lawson L, Churg A. Malignant mesothelioma caused b y childhood exposure to long-fiber low aspect ratio trem olite. Am J Ind Med 1988; 9:529-533. 41. Brown DP, Dement JM, Wagoner JK. M ortality p a tte rn s among miners and millers occupationally exposed to asbestiform talc. Proceedings of th e Conference on Occupational Exposures to Fibrous and Particulate Dusts and T heir Extension Into the Environment. In: Dusts and Disease. Park Forest South, Illinois: Pathotox, 1979; 317-324. 42. Smith WE. A sbestos, talc and n itrite s in relation to gastric cancer. (U nder the heading: "Industrial Hygiene Summary Reports" , a category meant for ". . . b rief comments derived from daily activities") . Am Hyg Assoc J 1973; 34:227-228. 43. Smith WE, H ubert DD. The in trap leu ral route as a means for estim ating carcinogenicity. International Symposium held at the Battelle Seattle Research Center, Seattle, June 23-26, 1974. In: Experimental Lung Cancer: Carcinogenesis and Bioassays. New York: Springer-V erlag, 1974; 92-101. 44. Smith WE. Experim ental studies on biological effects of tremolite talc on ham sters. In: Proceedings of the Symposium on Talc. Washington: U.S. B ureau of Mines, A. Goodwin, Information Circular #8639, 1974; 43- 48. 45. Smith WE, H ubert DD, Sobel HJ, M arquet E. Biologic tests of trem olite in ham sters. Proceedings of the Conference on Occupational Exposures to Fibrous and Particulate Dusts and Their Extension Into the Environment. In: D usts and. Disease. P ark Forest South, Illinois: Pathotox, 1979; 335-339; 341-355 46. Stanton MF, Wrench C. Mechanisms of mesothelioma induction with asbestos and fibrous glass. J Natl Cancer Inst 1972; 48:797-821. 19 CAMC-Abeyta-002380 47. Stanton MF, et al. C arcinogenicity of fib ro u s glass: pleural resp o n se in the ra t in relation to fiber dimension. J Natl Cancer Inst 1977; 58:587-603. 48. Stanton MF, et al. Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous m inerals. J Natl Cancer Inst 1981;67:965-975. 49. H arington JS. Guest Editorial. Fiber carcinogenesis: epidemiologic observations and the Stanton hypothesis. J Natl Cancer Inst 1981; 67:977-988. 50. Viagner JC , et al. Biological effects of trem olite. B r J Cancer 1982; 45:352-360. . 51. Davis JMG, Addison J , Bolton RE, Donaldson K, Jones AD, Miller BG. Inhalation studies on the effects of tremolite and brucite d u st. Carcinogenesis 1985; 6:667-674. 52. Vagner JC , G riffiths DM, Munday DE. R ecent investigations in animals and hum ans. In: Viagner JC ( e d ) , The Biological Effects of C hrysotile. Accomplishments in Oncology 1987 ; 1 (2 ) :11 -120. 53. L anger AM, Nolan RP. The p ro p erties of c h ry so tile asbestos as determinants of biological activity: variations in cohort experience and disease sp ectra as related to mineral p ro p e rtie s. In: Viagner JC ( e d ) , The Biological Effects of C hrysotile. Accomplishments in Oncology 1987 ; . 1(2):30-51. 54. Case BVi, Sebastien P . Fibre levels in lu n g and correlation with air samples. In: Proceedings of Symposium on Mineral Fibres in the Non Occupational Environm ent. Lyon: IARC Scientific Publications, 1988 (in press). 55. Davis JMG. Commentary: on the statem ent b y Jacques D unnigan. Am J Ind Med 1988; 14:629-630. 56. Davis JMG, McDonald JC. Editorial. Low level exposure to asbestos: Is th ere a ris k ? B r J ln d Med 1988; 45:505-508. 57. L anger, AM, Rohl AN, Violff MS, Selikoff IJ . A sbestos, fibrous m inerals and acicular cleavage fragments: nomenclature and biological p ro p erties. In: Lemen R, Dement JM ( e d s ) , Dusts and D isease. P ark Forest South, Illinois: Pathotox Publishers, 1979; 1-22. 58. Campbell 'WJ,. Steel EB, V irta RL, E isner MH. C haracterization of cleavage fragm ents and asbestif orm amphibole p a rtic u la te s. In : Lemen R , Dement JM ( e d s ) , D usts and Disease. P ark F orest South, Illinois: Pathotox Publishers, 1979; 275-286. 20 CAMC-Abeyta-002381 59- Vlylie AG, V irta RL, R ussek E. C haracterizing and discrim inating airborne amphibole cleavage fragments and amosite fibers: implications for the NIOSH m ethod. Am Ind Hyg Assoc J 1985; 46:197-201. 60. Vlylie AG, V irta RL, Segreti JM. C haracterization of mineral populations by index fiber: implications fo r the Stanton h y p o th esis. Environ Res 1987; 43:427-439. 61. Vlylie AG. Testim ony to OSHA reg ard in g mineralogie characteristics of asbestos. h U G_ G '9 0 16 :2 5 -- 21 . . _ -- -- ~ zl CAMC-Abeyta-002382 'This Statement was prepared by a Sub-Committee of the A T S Scientific on Environmental and O f. >,s` tonal Health." Members of the Committee ait=: CQMMITTEF MEMBERS: Hans Wk-.:. . D . .-i iAI F. Jerrola L. Abraham, M.D. John R. Balmes, M.D. Bruce Case, M.D. Andrew M. C h urg , Ph.D. Janet Hughes, Ph.D . Marc Schenker, M .D. Patrick Sebastien, Ph.D. " hUG _S " 9 0 16 : 2 G CAMC-Abeyta-002383