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AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 50:232-256 (1=55/ Chrysotile Asbestos is the~iV1ain Cause of Pleural Mesothelioma Allan H. Smith, md, PhD, and Catherine C. Wright, mph In contrast to amphiboleforms of asbestos, chrysotile asbestos is often claimed to be only a minor cause of malignant pleural mesothelioma, a highly fatal cancer of the lining of the thoracic cavity. In this article we examine the evidence from animal and human studies that relates to this issue. Reported data do not support widely quoted views regarding the relative inertness of chrysotile fibers in mesothelioma causation. In fact, examination ofall pertinent studies makes it clear that chrysotile asbestos is similar in potency to amphibole asbestos. Since asbestos is the major cause of mesothelioma, and chrysotile constitutes 957a of alt asbestos use world wide, it can be concluded that chrysotile asbestos is the main cause of pleural mesothelioma in humans. 1996 Wiity-Uss. Inc. KEY WORDS: chrysotile, asbestos, mesothelioma, epidemiological studies, animal stud ies, amphibole hypothesis, Stanton hypothesis INTRODUCTION Asbestos inhalation is an established cause of cancer in humans, particularly malignant mesothelioma and lung can cer. It is the main cause of cancer resulting from workplace exposure to carcinogens. . . Despite extensive cancer studies in humans, certain controversies remain about asbestos exposure and human cancer. The primary controversy is the question of fiber type in causation of mesothelioma. Commercial use of asbestos mainly involves the two amphibole fiber types, crocidolite and amosiie. and one serpentine fiber type, chrysotile. How ever. chrysotile asbestos is often contaminated with small amounts of tremolite. an amphibole fiber. The key questions concern whether or not. and to what extent, exposure to chrysotile asbestos (including its natural contaminant trem- oiite) causes mesothelioma in humans. White there is evi dence that chrysotile asbestos is not a potent cause of ma lignant peritoneal mesothelioma [EPA. 1986: Doll and Peto. 1935], the. role of chrysotile in the causation of pleural mesothelioma is still disputed. . Senool of Public Hesiui. University of Cililomij. BtriMley, CA. At*ess repnnt requests to Allan H. Smith. M.Q. ?n.Q.. Professor of EoitJemio/oqy. School of Public Health. University of California. Berxeley. CA 94720. Accesfed for publication January 26. 1996. Chrysotile asbestos is established to be a cause of asbestosis and lung cancer. In fact, one of the highest risks of asbestos-related lung'cancer was observed in textile manu facturing where 100% chrysotile was used (Dement et al.. 1994). However, the opinion is held by some that chrysotile asbestos is much less hazardous than crocidolite. amosite. and tremolite. particularly where malignant mesothelioma is concerned. McDonald ec al. (19891 state: "Amphibole as bestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile. very few." Wagner [1991] states: "There is overwhelming evidence that crocidolite is the main fibre associated with mesotheliomas. There is no clear evidence that exposure touncoritaminated chrysotile or anthophyilite is associated iwich these tumors." Two recent articles, however, have con cluded that chrysotile is. in fact, an important cause of ma lignant mesothelioma [Huncharek. 1994; Nicholson and Landrigan. 1994]. Nicholson and Landrigan conducted a thorough review of the evidence concerning the carcinoge nicity of chrysotile asbestos. In particular, they utilized the strong time dependence of mesothelioma risk to apportion, the contribution of the different exposure periods, and thus of different fiber types, to the observed risk. Huncharek addresses some current controversial issues surrounding as bestos health effects and their relationship to cancer risk assessment and risk management. As these articles point out. the question of the carcinogenic potential of chrysotile I 1996 Wiley-Uss. Inc. Chr/sotile 4sbes:cs anc Mesctheiicma 253 asbestos is noc only of scientific interest, but also has legal, public policy, and public health importance. The purpose of this paper is to further examine both human and animal evidence concerning the importance of chrysotile asbestos in causing malignant pleural mesothe lioma. Specifica.ly. we have identified the 25 epidemiologic cohort studies having the highest ratio of pleural mesothe liomas per 1.003 deaths, and have assessed the type(s) of asbestos fiber exposure in the highest risk cohorts. We have also reviewed those lines of evidence often cited in support of the theory that amphibole asbestos, not chrysolite, is the primary, if not sole, cause of malignant mesothelioma. Such lines of evidence include: results of certain epidemiological studies (such as the gas mask studies), and the "Stanton" and ''amphibole" hypotheses. '- A REVIEW OF THE EPIDEMIOLOGICAL DATA - A review cf the literature was undertaken to identify available asbestos epidemiological studies. Cohort studies (most recent follow-up available as of October 1994) were reviewed for the following data: industry, primary asbestos exposure (the fiber type to which the cohort or subcohort had the greatest exposure), secondary asbestos exposure (fi ber types to which the cohort or subcohort had lesser expo sure). number of workers in the cohort, number of deaths, number of lung cancer deaths, excess lung cancer deaths, and numbers of mesotheliomas. Pleural mesothelioma inci dence within the cohort was determined in terms of the number of pleural mesothelioma deaths per 1.000 deaths as well as the ratio of pleural mesotheliomas to excess lung cancer deaths. When possible, the mortality data for subco horts with greater than or equal to 20 years since start of employment were used in determining mesothelioma inci dence. Cohorts were rank ordered from the highest to lowest ratio of pleural mesotheliomas per 1.000 deaths. Table I summarizes the data for the 25 top-ranking asbestos cohorts. Other studies which were considered but which ranked below the top 25 cohorts are listed in Table II. Chrysotile was the primary exposure for at least two of the 10 top-ranking cohorts [Mancuso. 1988; Peto et al.. 1985] and was the secondary exposure or identified as part of a mixed exposure in six of the 10 top-ranking cohorts. Crocidolite was the primary exposure for three of the top 10 cohorts [Jones et al.. 1980: Talcott et ai,, 1989: McDonald and McDonald. 1978] and was the secondary exposure or identified as part of a mixed exposure in another five co horts. Amosite was identified as part of a mixed exposure in three of the top 10 cohorts, but was not the primary expo sure in any of them. These findings suggest that chrysotile is a major cause of pleural mesotheliomx They are incon sistent with the claim that amphibole fibers are much more potent than chrysotile. If that were the case, one would expect all the top 10 risk cohorts to be predominantly amphibole exposure cohorts. The highest ratio of S3.1 pleural mesotheliomas per 1.000 deaths was for railroad machinists exposed :o chrysotile [Mancuso. 19831. This study has been criticized for attributing the mesothelioma incidence to chr/sotile ex posure rather ihan possible amphibole exposure [Ohlson. 1989: McDonald and McDonald. 1989: Churg and Green. 19901- Mancuso's responses to such criticism demonstrate that the principal exposure of the railroad machinists was to lagging or removal of lagging, which was chrysotile. While other jobs may have used amphiooles. leading to the pos sibility of secondary exposure to the railroad workers, he made 1 strong case that chrysotile was the overwhelming exposure to the machinists [Mancuso, I989a.b. 1990). A number of other epidemiological studies have been published but lack data that would allow calculation of pleu ral mesothelioma incidence. Begin et al. [1992] described a series of mesothelioma cases in Canadian asbestos workers. All of these cases were seen and accepted by the Quebec Workman,'s Compensation Board for work-related compen sation of industrial disease. There were 49 cases in miners and millers of the Quebec Eastern Township region. Twenty mesotheliomas occurred in miners and millers from Asbes tos. where tremolite contamination was similar to back ground urban levels. Twenty-nine mesotheliomas occurred in workers from Thetford Mines, where higher levels of tremolite occur. Tne authors stated that, on the basis of the number of workers exposed at each mine site, the inci dences in Asbestos and Thetford Mines were similar despite the differing levels of tremolite contamination. McDonald al. [1980. 1993] conducted a cohort study of the miners and millers from Thetford Mines and Asbestos. Only 33 (25 in the period 1976-1988) mesotheliomas have been identi fied in the entire cohort of about 11.000 men. 30% of whom had died as of 1992. According to the authors, preliminary analysis of mesotheliomas suggests that the risk of mesothe lioma was higher in the mine and mills at Thetford Mines (higher tremolite exposure) than in chose at Asbestos (lower tremolice exposure). Their data, however, do noc clearly support this conclusion, especially in the high exposure groups where the rates of mesothelioma were 0.97 per 1.000 person-years for Asbestos and 0.92 per 1.000 person-years for Thetford Mines. A number of other studies have demonstrated risks of mesothelioma due to chrysotile exposure. Borow et al. [1973] reported 72 cases of malignant mesothelioma in per sons exposed primarily to chrysotile in an asbestos mill. Fifty-three acceptable cases of chrysotile-induced mesothe liomas were identified by Churg et al. [1988]. Two malig nant mesorhettomas were reported in a small group of former chrysotile miners and millers in Zimbabwe [Cullen and Baloyi. 1991]. A case series of 80 mesotheliomas in railroad rolling-stock machinists and others in the Italian 254 Smith and Wright TABLE I. Asbestos Cohort Studies Aitirtflca fnlesry Wn>pf ItttflQ tzeosurt Secondary uoatus ont Xemkir : (snort Mvmaer ud ol 3tr deatns eatr*s tins* 'oaq canon cmout. floral miieiR. ?f, nil/ t.OOQ eyaifts rt. omo/n >**% canon ,, CimmtAtt .`.tancusa I'SMI Railroad .rucnnuo CMrys Possio* ' torn* impmbou 181 159 n HA 1 14 811 Ankatstam i1M-| Jones it eL i'JMI Taiccn it iL (1949) glmes ana Simoson (U77t Psto tl aL (W5| Cameffl c/aaua Gas mask manuiaeava CoartRt Atcr manufacran Insula don (U99inl Qwyst croc Croc Doc Unknown (MX Ttftiha Ouya Doe MeOonaia ana McOena/d |H73| Gai mask Doc ma/Hi&ean Or# 6U 136 95 J 185 23 28 162 in 29 21.4 12 17 11 104 24 HA 1 `4 3 5 14$ 123 20 UJ 0 11 80.9 13 784 2 71.4 8 85.6 7 119 199 58 r 4.8 9 3 518 ,`fCWAOOtt al. (t98S| Hewflovii ct aL p995] flrtliV cement products lujgen SltikoK It tt. (1979i| Ship/a/d Miked imos/ eflryst C/oc Mixed a/noV enryj/ croc Chryif amps TOO 1.400 389 $lns Cramer Uintng t a (1992) Doe 1430 Nicholson ilS7Sj Armttronq $t aL (I9U| HtwNnm it at [1943] Seidman ana SailOil (1990J Aossiter it aL (1980| Alain et aL (iwi| Seidman it aL (!9Mi . Peto it at (1983) Sluis-Dimer ii at. (1992| ?rodue3on and tenUs Mimu)/ miUina Ttxoleof earnim p/DOtxa Imuboon Hot staled Doe Mbed amoar cfuysr croc Chrjn Shipyards Mated Asbestos c*(nim ma/Hibcairt insulation manut. Times Chryi Amos Guys Uirinq Mbed ampn Amos Crocftmo* Doe 889 8.508 1000 17.800 8.078 1.438 820 3411 (73 Nrwnousi ana Suttivan {19891 Kolontl it j|, (1985] Actoson < al. (f984( n-ictien matemrt Guys SDieyirti Guys kuutadon Ames mamtbetero Doe Ames U22 1191 1.120 AcmaoA tt at (I982J Gil mask Croc lurtvfeauri 757 Ratlin n *L (11 Maiiuf. UR. cement Ckrys Amos/croc 7.998 274 157 n *13 199 820 111 4.931 1.043 392 368 727 154 743 6U 333 219 1.303 37 310 tl It 17 3 6 20 24.9 27 117 27 t U 91 158 94.1 3 2 7 1 29 MSI 899.3 289 M -18.3 35 118 Z 0 78 93 XA 82.8 2U HA 9 3 18 17 NA II *9 57 27.4 13 6.1 1 162 712 7 * 0 0 14 S1.1 7 U.6 3 41.1 17 *04 8 412 13 39.0 31 37J 173 34.9 29 27.1 11 22.0 1 10 --2 9 1 4 21.9 115 13.0 HI 110 110 2 9,1 to . 7.7 HA 051 129 ixeecro 'u/wj oe ceatni -ere tot icorrea. Prunarvy serving 31 uaam ecomeevrs. Greater than *0 ?jrs vnex first imotoyment Marcuse |1S49| imoruacfi rui jnrcteaJ (xaosura <nj Uqciru} or r*mua c< Uqguiq. men was cvyiooro. However. 3tntr rooi may ,*jvt used amcntooies. to iceo/ioar/ exsosurt t Soxnai*. 21* years from oamL Preoucscn inc mare/enance. 20* years ."ram onset .^atn an*. 019 HA 048 0.85 044 20* years .Ycm onset. Seven MdHional twnq cancers or .smccniAemas ccuid 'ct b* cateqorcto. :?A (I9B6( lisa 27 cos.. 22 txeau lunq arcztt lor dus conoa Subeofwrt men on*, rmotoyed 20* years widi semo serve* befon t331 Hiqn txpojgrt frond. CroodolKe made *jo 5" ai uaositt oad ^rwem 1932 wu '>99. Males rod rtmaus comcined. 23-16 years smc4 onset of irocsurs to croodcnte. Doesuro ro cnryMSie Acer io nave occurred bercre <n titer. Car*an mduees worurs from avee (ictones, riitar >aa wcrtaii m Montreat |R 321 were iidqiis 10 croc *cm 11*G ic 6/*1 on*. Hms iactonr used cnryteoie unci *928 tor (Tunoi. a1 :rs*e knwfqs. RHtr wonea Irent Asn*s:os. Oueoic |n 113} were ix90MO :a croc I93&-941 eixy. This factory naa <n ccersdon since vvv/1 processmf c/vysoote. Gas mask usetno* was Mrtomwd in Ottawa (A 34). An addioenal rwo cases d aieurat Rinemeeonu from Menireai punt *? identided from a nail sur/iy. Hcu mat TaW 2 <t McOonatd uvi M^onald (19? J| incomes/ prtsena fwe ftte*irai mesctneiiQRULS. Women on*. Grsster sun to years Joflow-jp. 028 Mm only. Gtestit *an to yean JoHow-ja. *io romowte caa -or 20* rears smci 1 it tmotoy. 012 12* 0.43 Shidyardtniuufar C3nc/C 29* mrs .`rcm onjL Aros.*3 aoeed .'0 cnrysoo>< ;ust Dc/ore ana :unnq wwu. Cohen ol mmers isaoitd on* to craudOMs. Ho suKoncn data for 20* yiart smee tst imeioy. 20* ytits Item cash. 047 033 Mm only, tnervees tnnr* canon. Uotfate :o M008S It 3L f 19S0U Men on*. >10 years tefme-vo. 019 -148 liore conon. Wemirs rte Mooted cn*s m sany yun and &vys amos in tatir yiars. 0.93 013 035 HA 158 20-40 daps id years smci onset at wool Subconod of man first improved hi 1933 or later. 20* years tmet 1st tmeroy. Cohen et mm*n asposad to mmo imemhctes: rSo numcir of at mtsoi csmc 9e two or sm. Uneiar 20* r*4/s Item seL 1.63 OIS 0.29 014 Neneaeosed ;rcu tteudid. Includes ad tanner :mees. mcuots vo ot. mesoifi. mm tss sun 20 yean smci luu UMttttl. Doedooip canon sn*. Some ;r.dun cnysoote fas masks wen atso maoe sy cus canon. 89^. cnrysoBfc ssed. t00* enr.s :l25-5 ai. Chrysotile Asbestos and Mesothelioma 2S5 TASLS II. Additional Studies Considered* Acheson et al. (1982]--chr/sohls cohort Cement et it. (1S32| ."niielsitm (1339| Henderson and-ecterline [1979| Hu-hes and Weill [1980] Hughes et aL (1987] McOonald ttal. [1980. 1993] McDonald et ai. (I983a| McOonald et al. {1283b j McDonald et al. (1984| Nic.ialson et at. (1979) Pio atto et al. [1990] Puntoni et il [1979] Robinson et al. [1979] Sluis-Cremer et al. [1992]--amosite cohort Thomas et al. [1982] Weill et aL [1979] Weiss [1977] `SNcitti whicil weft rtviewed 5uf wen not in* ctoded ift Titi11 dve ?o low ratios of pteuoi mtsouiefiomu IQ total Quins. (978; Acheson e: al.. 1982]. The expected number of lung cancer deaths for the McDonald and McDonald [1973] study was not given, but we have assumed it was one since it makes very little difference to the overall consideration of the studies. The last row of Table III gives the summed data from the three gas mask studies. Tnere were 19 pleural mesothe lioma cases in the crocidolite group with a lung cancer excess of about 13.5. There was only one case in the chrysotile-only category, but the excess lung cancer number was only 1.2. Since chrysotile is a potent cause of lung cancer, this low excess makes it clear that the chrysotile gas mask workers had relatively low exposures. In fact, the total length of exposure to chrysotile in the Jones et al. study was shorter than 5 months. In the Acheson study, the exposure to chrysotile was probably much lower than the exposure to crocidolite, since the crocidolite filters were made by hand while the manufacture of chrysotile filters was mechanized. Thus these three studies provide no evidence whatsoever that crocidolite is more potent in causing mesothelioma than chrysotile asbestos. Fiber Type Risk Comparisons railroad industry, where chrysotile was the primary expo sure, has also been reported (Maltoni et al.. 19911. Fifty malignant mesothelioma cases have been identified in the manufacturing, insulation, and shipbuilding trades, and 21 cases in the construction and building maintenance trades [Begin et al.. t992|.cpr3lsbfi'i2iese'.tnSies;'cfi^s9tilb con stituted the primary exposure and amphiboles the secondary exposure: Sanden eta/. [1992] conducted acancer incidence study of shipyard workers exposed primarily to chrysotile. with lesser exposure to amosite and crocidolite. Eleven of the 168 cancers were pleural mesothelioma, including eight of the 70 cancers in persons with 20 or more years latency. In addition, eight cases of malignant mesothelioma were reported following household exposure to the duscy clothing of asbestos workers [McDonald and McDonald. 1980]. Three of these eight cases were children of chrysotile mine employees. The above data demonstrate that chrysotile ex posure, even at the relatively low levels expected in house hold exposures, can cause malignant mesothelioma. Gas Mask Studies Studies of workers who assembled gas masks during World War II have been widely quoted as indicating that crocidolite is much more potent than chrysotile asbestos in causing mesothelioma (Doll and Peto, 1985: Harington. 1991], Table HI presents data abstracted from the three gas mask studies where workers have been exposed to one fiber type only (Jones et al.. 1980: McDonald and McDonald. Hughes and Weill [1986] have suggested that crocido lite is about 14 times more potent than chrysotile in causing combined pleural and peritoneal mesotheliomas. This find ing is based on combined data from selected cohorts with chrysotile. amosite. crocidolite. or mixed exposures. The results indicated that the number of mesotheliomas was 12% of the excess lung cancers among chrysotile-exposed populations, but 165% for crocidolite exposure, 22.2% for amosite exposure, and 65.9% for mixed fiber exposure. Table IV presents our reanalysis of the above findings. The same cohorts are included, but the most recent fol low-up data from these cohorts were used in the analysis. Where possible, data from subcohorrs wich 20+ years since first exposure were used. Furthermore, since it is generally agreed that chrysotile asbestos is not a potent cause of peri toneal mesotheliomas, only pleural mesotheliomas are in cluded in the table. Our analysis indicates very different results from Hughes and Weill [ 1986]. The number of pleu ral mesotheliomas is 20% of the excess lung cancers among chrysodle-exposed populations, 72% for crocidolite expo sure. 13% for amosite exposure, and 27% for mixed expo sures. The longer follow-up period makes a large difference between the Hughes and Weill [1986] analysis and that presented here. Rather than appearing to be 14 times less potent thafl'crocidolite. based on this selection ot studies chrysotile may be only three or four times less potent in causing malignant mesothelioma. This is inclose agreement with the conclusions of Nicholson [ 1991 ]. who looked at comparative dose-response relationships of asbestos fiber 2SS Smich and Wright TABLE III. Pleural Mesotheliomas. lung Cancer. and Excess Lung Cancers in Gas Mask Manufacturers Using Cnly Crocidolile or Cnly Chr/sonle Crocidolite only CMrysatile only Pleural mesotheliomas Lung cancer Excess lung cancers Pleural mesoltiellomas lung cancer Excess lung cancers McDonald and McDonald [1973]' Jones it al. [1930| Acheson et al. [1S82] Total 1 15 3 19 zt 11 5.7 13 6.3 25 13.5 - _-- 0 01 6 1.2 1 6 1.2 `Otmra conon wnn exposure lo crocidolite only. types and included more studies than Hughes and Weill [1986]. His conclusion was: that "There appears to be no difference in the potency of chrysotile and amosite in pro ducing mesothelioma. However, exposures to pure crocidolite. which has been and is rarely used in the U.S.. may carry a two- to three-fold greater risk" [Nicholson. 19911. To summarize the epidemiological findings as they re late to chrysotile and pleural mesothelioma, the following points can be made: (l) If crocidolite were much more potent, the highest mesothelioma risk cohorts should in volve predominantly exposure to crocidolite. In fact, the highest risk cohorts do not show this differentiation. (2) Limited data concerning exposure of household members suggest chrysotile is a highly potent cause of mesothelioma. (3) The widely quoted gas mask workers studies do not provide evidence that crocidolite is more potent than chry sotile. (4) Considered overall, the evidence suggests chryso tile may be less potent than crocidolite by a factor in the range of 2-4. However, the epidemiological evidence does not support chrysotile being less potent than amosite. A REVIEW OF AVAILABLE ANIMAL DATA Chrysotile. amosite. crocidolite. and tremolite can cause pleural mesotheliomas in experimental animals ex posed by inhalation, intrapleural injection, or surgical im plantation. Table V summarizes data from long-term studies of experimental animals exposed via inhalation, the most relevant route for human exposure. In order to get an overall incidence of pleural mesothe liomas in rats following inhalation, incidence data were added together for each of the three asbestos types (i.e.. chrysotile. amosite. and crocidolite). The overall incidence of pleural mesothelioma in rats exposed via inhalation is 1.3% (13/733) for chrysotile, 1.3% (5/377) for amosite. and 1.2% (4/323) for crocidolite. Thus, inhalation studies in rats do not support the argument that chrystotile is far less po tent than amphiboles in pleural mesothelioma causation. Since only one inhalation experiment has been done for tremolite. it is not included in this comparison. Intrapleural injection studies have also demonstrated that chrysotile is a potent cause of pleural mesotheliomas in rats [Reeves et al.. 1971: Wagner et al.. 1973]. in fact. Wagner et al. found that finely milled chrysotile was more potent than the crocidolite and amosite samples tested. Surgical pleural implantation of fine chrysotile. croci dolite. amosite, or tremoiite fibers also induced significant numbers of pleural sarcomas in rats [Stanton et al.. 1972. 1981]. The cumulative incidence of deaths with mesothe lioma from chrysotile, amosite. and two types of crocidolile was similar at the maximum dose level of 40 mg [Stanton et al.. 1972]. ~ In conclusion, there is clear evidence in animal inhala tion and pleural injection/implantation studies that chryso tile asbestos causes pleural mesothelioma. Indeed, if one considers the dose of asbestos in terms of mass, chrysotile asbestos is generally the more-potent fiber when-compared to crocidolite and amosite. However, the data do not permit estimation of potency per fiber. The data for tremolite is quite limited, but do not support the conclusion that trem olite is a more potent mesotheliai carcinogen than chry sotile. THE STANTON AND AMPHIBOLE HYPOTHESES REVISITED Two lines of evidence have led some researchers to believe, that chrysotile is not an important cause of pleural mesothelioma in asbestos workers, and that the risk is at tributable to amphibole exposure. The "Stanton Hypothe sis" suggests that mesothelioma incidence is strongly correlated with longer, thinner fibers. The " Amphiboie Hy pothesis" states that amphibole fibers are responsible for causing mesothelioma, since these fibers are found in the lunss of mesothelioma cases at autopsy, but chrysotile fi bers are not. The evidence leading to these hypotheses is summarized below. Chrysotile Asbestos and Mesothelioma 257 TABLE IV. Mesothelioma in Populations Exposed to Different Tiber Types'0 Fiber type ChrysotileAmasite1 Crocidolite* Mixed liber* Observed deaths 10.245 1.153 1.042 9.532 Luno cancer Observed creess 725 133 110 1.722 186.9 90.2 66.8 1.106.2 Pleural mesothelioma Obserred As V. ol excess lumj cancer 39 20.3 12 13.3 48 71.9 301 27.2 3ata on TiOle I of Hupnes ana V/eiU (1985). . 'induces suoconons wun 20 years since first employment where possible. 'McDonald et at. (1933.5984. I993|, McDonald and McDonald [1930], Aubmo et at. (1979], Piolatra et al. (19901. Whss {19771, Acr-eson et at. {1932J. Thomas et al. (19821. 'Saidman et at. (1979. 1986], Acfteson et at. [1984). hoods et al. [l980|..Artrstrong et al. (19331. McDonald and McOanald (I978|, Jones et aL (1980]. 'McOonaid et aL (t983|. 3rry and Newhouse (19831. Newnouse and Sullivan (19891. SeUkoH et at. (19791. Seidman and Selikolt (12901. Aeneson et al. (19821. Hewnpuse and Berry (1979). Newnouse et al. (19851, Finkefstein [1983. 1SS4|, Bmes and Simpson (1977], Thomas al. [1932], Sossiler and Caies (1980|. Stanton and his colleagues conducted a series of exper iments in which a number of durable minerals in the form of respirable particles were implanted in the pleura of rats for periods of more than I year [Stanton and Wrench. 1972: Stanton. 1973: Stanton et al.. 1977. 1981). Significant num bers of pleural sarcomas were induced in rats with a wide variety of fine, durable fibers including chrysotile. crocidolite. amosite. and tremolite. The two earlier studies showed no difference in potency between standard UICC samples of chrysotile and crocidolite [Stanton and Wrench. 1972: Stan ton. 1973]. The primary conclusion of these studies was that the ability of mineral panicles to cause tumors is mostly a function of the dimensional propenies of the panicles, rather than physicochemical propenies. Tne later studies, which did not include chrysotile. at tempted to funher characterize the imponance of dimen sional aspects of fibers [Stanton et al.. 1977.1981]. Accord-, ing to the authors, the incidence of malignant mesenchymal neoplasms correlated well with the dimensional distribution of the panicles. The probability of pleural sarcoma corre lated best with the number of fibers that measured 0.25 tim or less in diameter and more than 8 pm in length. Relatively high correlations were also observed with fibers in other categories having a diameter up to IJ pm and a length of greater than 4 pm. This evidence led to the "Stanton Hypothesis," which states that durable fibers (provided they subscribe to well defined ranges of diameter and length), of which asbestos is but one sample, cause cancer irrespective of their physico chemical nature simply because they are fibers. Stanton also staled, however, that direct application of the results of his experiments to the problems in humans would be unwise given the deficiencies in the method of application and the massive amounts of fibers used (standard dose. 40 mg). In fact, if one were to exclude alt fiber types other than asbes tos from Stanton's data, there appears to be little or no relationship between the probability of tumor and the num ber of particles measuring <0.25 pm diameter and >3 pm length (Fig. I). Other researchers have studied the correlation between dimensional properties of fibers and mesothelioma. In ex periments similar to Stanton's. Jaurand [1991] determined the percentage of mesotheliomas occurring after intrapleu ral inoculation of 20 mg asbestos samples into rats. She found a fairly good correlation (r = 0.643. p < 0.01) between the risk of mesothelioma and the number of ''index'' fibers (i.e.. <0.25 pm diameter and >8 pm length) inoculated ac cording to Stanton's criteria. However, there was only a 30% difference (20% vs. 50%) between the percentage of mesotheliomas produced by samples with the smallest num ber of index particles compared to samples with a higher number of index panicles. Furthermore, when Jaurand [19911 combined all of her available data from previous studies of amosite, crocidolite. and chrysotile (Monchaux et al., 1981], there was no correlation between the percentage of mesotheliomas and the number of index panicles (,r = 0.164).. Despite Stanton's warning and the findings described above, many researchers have utilized the Stanton hypoth esis to link mesothelioma cases to panicular asbestos fiber types and sizes. Churg. for example, stated: "Given the very high exposures experienced by the Quebec workforce, the short size and low aspect ratio of the tremolite fibers found in the ore may be a fortunate accident which 'pro tects' these workers from mesothelioma" [Churg. !9SS|. Churg's statement, however, also assumes that it is the tremolite. not the chrysotile. that is responsible for those mesotheliomas that did occur. This assumption is based on the finding that, although tremolite comprises only a tiny fraction ofthe asbestos dust in the Quebec mines and mills. 253 Smith and Wright TABLE Long-Term Asbestos Innaladon Studies in Animals Reference Species Fiber type Reeves el at. [I97ff"* Wagner et al. [1974] Retvts el al. [1974] Davis et al. [1378] Davis et al. [1985] Oavis et al. [1986a] Davis et al. [1986b] Davis and Jones [1988] Total Rats Rabbits G. pigs Hamsters Rats Rats Gerbils Rats Rats Rats Rats Rats Rats Amos Croc Chrys Amos Croc Chrys Amos Croc Chrys Amos Croc Chrys Amos Croc Chrys (Can.)' Chrys (Rh.)' Chrys Croc Amos Chrys Croc Amos ' Chrys (Rh.) Chrys (Rh.) Amos Croc Croc Tremotite (Kor.)' Short amas Long imos WOC yam" Factory WOC Chrys yam* Exp WOC* Exp WOC/RO* Short chrys Long chrys Chrys Amos Croc 'Mo pleural mesotheliomas wen observed in any control group. 'Similar doses in mg/m1 may Pi very different In terms of libers/mf. 'MesorheSoma occurred with just 1 day esoosure (>2 years followuol. 'One mesoifieiioma occurred wirft just 1 day uoosuri (>2 yean followup). HD. Rhodesian. 'Can. Canadian. 'Kor. Korean. "'/TOC is *et dispersed chrysotlit. Oust from factory air. 'Standard chrysodle India yam. "Ssoerimemal WOC process, tsoerimennl WOC 'reversed daylight" Dose1-* mg/m" Humber tested -48 -48 -48 -48 -48 -48 -48 -48 -48 -48 -48 -48 11-14 10-13 10-12 10-15 -50 -50 -50 -50 -50 -50 2 10 10 S 10 7 10 . to 4 4 4 4 4 10 10 ' S3 51 49 20 13 26 17 33 21 50 45 49 146 141 137 144 34 43 43 40 31 45 42 . <o 43 43 40 40 42 40 41 44 42 37 40 40 733 377 323 . No. ot pleural mesotheliomas 0 0 0 0 0 0 0 0 0 0 0 0 le 3* 4 0 1 0 2 0 ' 0 0 ' 0 0 0 . ... J - 0 2 0 2 0 0 1 4 t 0 2 13 (t.a%) 5 (t.3%) 4(1.2%) Chrysolite Asbestos and Mesothelioma 259 11 0.9 - 0.3 - 0.7 0.S 0.5 0.4 0.3 - 0.2 0.1 | . *" * 0 \-------------------------i------------------------- 1-------------------------i-------------------------1-------------------------i-------------------------- 1 0 1 23 4 5 6 FIGURE 1. Stanton et at. (1981) data lor asbestos fibers only. X-axis: Log number panicles measuring s0.25 um wiatn by >8 pm lengm per microgram. X-axis: Probability o( tumor. . tremolite: Q amosite: . cracidolite. high tremolite lung burdens were associated with the pres ence of mesothelioma in miners and millets from Thettord Mines (Churg, 1994], After adjustment for the presence of tremolite. no correlations between chrysotile concentration and disease could be found. This leads us to the ``amphibole hypothesis." which attributes the mesotheliomas observed in various groups of workers to the asbestos fibers present in their lungs at the time of death rather than to the fiber exposure earlier in life [McDonald ec al.. 1989: Mossman et aL 1990; Churg, 1988], The ``amphibole hypothesis" is based on the find ings that workers exposed to asbestos have more amphi- boles in their lungs than chrysotile at autopsy. This occurs because chrysotile fibers (but not amphiboles) break down and split apart longitudinally in tissue, leading to a loss of fibers in lung tissues that are visible by electron microscopy (Nicholson and Landrigan. 1994], Some suggest that some (if not most) of the chrysotile fibers further fragment into shoner fibers and are then cleared from the tunas [Churg, 19941. ' A number of studies have examined fiber content in lungs of mesothelioma cases. Those of Churg et al. (1984) and McDonald et al. [1989] are often referenced in support of the "amphibole hypothesis.'" Other important studies include Roggii et al. [1993], Morinaga etal. [1989], Rogers et al. (199rJ. and Sakai et al. (I994|. In fact, the results of these studies are inconsistent, as demonstrated in the fol lowing reviews. Lung tissues of six mesothelioma cases from the Que bec chrysotile mining regions were examined by Churg et al. [1984], The five cases that had only chrysotile ore comr ponents in their lungs had larger amounts of tremolite (i.e.. tremolite/actinolite/anthophyllite) than chrysotile. The mean levels of chrysotile and tremolite in mesothelioma cases were higher than their respective mean levels in nine chrysotile miners without mesothelioma or the mean levels in nonexposed controls. Assuming that the fibers present in lung tissue at autopsy are responsible for mesothelioma, this study would support the conclusion that tremolite is respon sible for the mesotheliomas occuring in this cohort. McDonald et al. [1989J examined lung tissue samples from 78 mesothelioma cases in Canada and from matched referents. Chrysotile fiber distributions in the two series were similar. Relative risk was related to the concentration of long amphibole Fibers'. The proportion of long amphibole and chrysotile fibers was higher in cases than referents. According to the authors, amphibole asbestos fibers could explain most mesothelioma cases in Canada, and other in organic fibers, including chrysotile. very few. McDonald et al. (1989} concluded that fibrous tremolite probably ex plained most cases in the Quebec mining region. In a more-recent study. Roggii et al. (1993} analyzed the mineral fiber content of the lungs in 94 patients with malignant mesothelioma from the United States. A large proportion of the cases were either insulators or shipyard workers. Only fibers that were greater than or equal to 3 urn 250 Smith and Wright in length were included in the analysis. Amosice was iden tified in 76 cases (31%). the noncommercial amphiboles (primarily iremolite) were identified in 52 cases (55%). chrysotils was detteted in 20 cases (21%). and crocidolite in 15 cases (16%). Another rive cases (5%) could not be distinguished between amosite and crocidolite. According to the authors, tremolite fibers are probably a marker for the much greater numbers of chrysotile fibers which were de posited but subsequendy cleared. Tne authors found that, assuming it is the fibers that accumulate within the lung that are responsible for the de velopment of mesothelioma, the order of importance of fi bers is amosite > tremolite > chrysotile = crocidolite. How ever. they were unable to exclude a greater role for the long chrysotile fibers found in their cases, especially since they probably constitute only a small fraction of the long fibers actually deposited. One issue raised was that the methods used might have underestimated the numbers of chrysodle fibers 5 p.m or greater in length, because chrysotile tends to undergo longitudinal splitting with many of the resulting fibers having diameters less than 0.1 urn. The techniques used in Roggli et al. primarily detected fibers that are 0.2 urn or greater in diameter. A study of asbestos fiber content of lungs with me sothelioma in Osaka, Japan was conducted by Morinasa et al. (1939). Chrysotile was observed in 1.2 of the 23 mesothe lioma cases, amosite in 13, crocidolite in three, and actinolite-tremolite in three-cases examined. Six of the mesothe lioma cases had only chrysotile fibers. This study provides evidence that, if indeed it is the fibers present in the luns at death that are responsible for mesothelioma, then chrysotile asbestos is a potent cause of this cancer. Rogers et ai. [1991] examined lung tissues from 221 definite and probable cases of malignant mesothelioma re ported to the Australian Mesothelioma Surveillance Pro gram. and from an age-sex frequency-matched control se ries of 359 postmortem cases. A progressive increase in relative risk with increasing fiber content was observed for all fiber content measures. The relative risks for chrysotile. crocidolite. and total amphibole fibers which were 10 (im or longer were greater than the corresponding risks for fibers less than 10 p.m in length. When cases and controls were compared in relation to exposure to single-fiber types only (all lengths), increased relative risks were observed for both chrysotile and crocidolite. Pulmonary fiber content was analyzed by Sakai et al. [1994] in 16 patients with malignant mesothelioma and in 16 case-matched controls. Amphibole. chrysotile. and nonas bestos fiber contents were significantly higher in patients than in the control subjects. Summary of Lung Content Studies The "amphibole hypothesis'' is based on (I) the as sumption that the fibers present in the lungs at death caused the mesothelioma, and (2) the finding that workers exposed to asbestos have more amphiboles in their lungs than chrysotile at autopsy. Chrysotile fibers break down and spite apart longitudinally in tissue and can be cleared from the lungs, while amphibole fibers are less attacked by body fluids and can be detected in the lungs of workers years after exposure [Nicholson and Landrigan. 1994], (n fact, complete fragmentation of a single chrysotile fiber may produce 1,000 fibrils [Wagner et al.. 1973], and these fibrils may be so thin that they are .no longer visible by electron microscopy in lung tissue. Results of the lung content studies described above are inconsistent, and do not resolve the question of the impor tance of fiber type in mesothelioma causation. Some studies report significant amounts of chrysotile fibers in lung tissue. Furthermore, the results of Morinaga et al. [1989] demon strate that mesothelioma can occur in the absence of am phibole fibers, since six cases had only chrysotile fibers in their lung tissues. The limitations of using lung content studies in deter mining the role of chrysotile in mesothelioma causation are as follows: (I) The methods used often exclude fibers less than 5 tim in length. (2) The potential for carcinogenic effects induced by large numbers of short fibers has not been investigated. (3) The methods may have underesti mated the number of long thin chrysotile fibers actually present in the lungs due to an inability to detect very thin fibers. (4) The number of chrysotile fibers counted consti tute only a minute proportion of the long fibers actually deposited and subsequently cleared. (5) Finding a signifi cant number of tremolite fibers would indicate a major ex posure to chrysotile. since iremolite is only a minor con taminant of chrysotile. Dement [1991] makes the obvious point that measure ments of lung fiber burdens made many years after first exposure may bear no relationship to the carcinogenic evems that took place long before clinical manifestation of disease (lung cancer or mesothelioma). In addition, the fi ber levels of tremolite measured in lung tissues of work ers exposed to chrysotile may be a surrogate measure of cumulative dose of chrysotile. Case [1991 j. on the other hand, states: "It is presumably necessary far fibers to be present in order for them to exert a carcinogenic effect.' This point is often missed by those who regard tremolite-- the more potent carcinogen--simply as a 'marker' for chrysotile." However, we cannot presume that the fibers present in the lunss at death are responsible for mesothelioma. In view of the long latency between asbestos exposure and mesothe lioma diagnosis (average of about 32 years in all studies), it is more likely that the effective target organ dose involves fibers in contact with the pleura many years before diagno sis. Data concerning fibers present in (he pleural space are considered below. Chrysotile Asbestos and Mesothelioma Pleural Content Studies A number of studies have addressed pleural fiber con tent. which is likely to be more biologically relevant to the development of asbestos-related pleural mesothelioma than lung tissue content. One study comparing the retention of asbestos fibers in parenchymal and pleural tissues found that lung parenchy mal retention is not a good indicator of pleural retention (Sebasiien et al.. 1980], Although amphibole-type fibers longer than 3 urn were present in lung parenchyma, in pa rietal pleural tissues short chrysotile fibers greatly outnum bered long fibers of the amphibole type. The retention of asbestos dusts in the parietal pleura was related to type and size: 84% of the chrysotile fibers in the parietal pleura were from 0.4 to 4 pm in length and from 0.03 to 0.25 pm in diameter. If the fiber content of the pleura is responsible for pleural mesothelioma, then this study suasests that chrysotile fibers would be more important than amphibolea in causation of this cancer. Tissue samples from 13 North American insulators were examined in order to investigate translocation of as bestos fibers (Kohyama and Suzuki. 1991], Tnese cases included three of asbestosis. three lung cancers, two malig nant pleural mesotheliomas, and five malignant peritoneal mesotheliomas. The authors concluded that (I) transloca tion of inhaled asbestos fibers from the lung to other organs, such as the pleura and the peritoneum, seemed to occur frequently among asbestos insulation workers, although the route of the translocation has not been completely investi gated: (2) chrysotile seemed to be more actively cleared from the lung and translocated into extra pulmonary tissues, compared with amosite: (3) chrysotile fibers cleared from the lung were not later eliminated from the host. The au thors suggested that biological effects of the translocated asbestos fibers may be significant, and translocated chrysotile fibers may play an important role in the induction of either malignant mesothelioma and/or hyaline plaques. Asbestos fibers detected in both mesothelia! tissue and hy aline plaques were mainly chrysotile. Data from a study- of lungs and pleurae of shipyard workers were reported by Bignon et ai. [1978J. Larger fi bers. often amphibole. were found in the lung tissue. In the pleura, the fibers were generally chrysotile. but shorter and thinner. Le Bouffant [1980] observed a preferential migration of chrysotile fibers to the pleura, with a significant increase and accumulation in the pleura in comparison with the lune parenchyma. The median percentage of chrysotile fibers was 3% in the lung and 33% in the pleura. Similar results have been demonstrated in rats [Viallat et al.. 1936], Fol lowing intratracheal injection of rats with small amounts of U1CC chrysotile. the shortest fibrils (mean lengths 0.44 1.32 um. diameter 0.03 uiml reached the pleura very rapidly and could be retrieved from the pleural fluid of rats .vithin I month. In summary, pleural content studies demonstrate :ha. chrysotile fibers preferentially reach the pleura and are the predominant fiber found at this target site in asbestos-ex posed humans. These findings are clearly more pertinent than lung content findings, and support chrysotile asbestos being a potent cause of pleural mesothelioma. CONTRIBUTION OF CHRYSOTILE ASBESTOS TO PLEURAL MESOTHELIOMA INCIDENCE In considering the contribution of chrysotile to pleural mesothelioma incidence, three factors will be addressed: (1) the'relative potency of the three commercial asbestos fiber types; (2) the proportion of pleural mesotheliomas due to asbestos exposure; and (3) the extent of chrysotile produc tion and use. Potency of Chrysotile To summarize the evidence presented concerning the potency of chrysotile asbestos in causing pleural mesothe lioma. the following points can be made: (I) Studies of asbestos-exposed workers provide evidence that the chryso tile and crocidolite forms of asbestos are major causes of pleural mesothelioma in humans. Crocidolite asbestos may be 2-4 times more potent than chrysotile and amosite. (2) In rodents, chrysotile. amosite. and crocidolite asbestos have similar potencies, both in inhalation studies and in pleural injection studies. (3) Reexamination of the data on which the Stanton Hypothesis is based demonstrates that the data do not support the hypothesis that long thin amphibole asbestos fibers are the most potent in causing mesothelio mas. (4) Studies of lung tissue on which the "Amphibole Hypothesis" is based are inconsistent. In any case, findings in lung tissue at the time of diagnosis have no relevance to causal events which take place decades earlier. (5) Pleural content studies demonstrate that chrysotile fibers preferen tially reach the pleural space, which is important since the pleura is the target site. Based on these points it can be concluded that chrysotile asbestos is a potent cause of pleural mesothe lioma. In light of the evidence regarding their relative po tencies. it is reasonable to make the same regulatory policies for each of the three primary asbestos fiber types. Proportion of Mesotheliomas Due to AsBestos There has been wide variation in estimates of the pro portions of mesotheliomas attributable to asbestos exposure. For example. Peterson et al. [1984] reviewed the literature 262 Smith and Wright and noted that the proportions linked to asbestos exposure ranged frorr. 13?# in two studies [Ratzeret al.. 1967; Bren ner ec al... 1982| to 100% in one study at the other extreme (Cochrane and Webster. 1973). They concluded that there were large numbers of apparently nonasbestos-related ma lignant mesotheliomas. Closer examination of the evidence does not support this conclusion. The studies which find a low proportion of cases linked to asbestos exposure tend to use poor exposure ascertainment methods, such as reviewing medical records (Ratzeret al.. 1967; Brenner et al.. 19821. Assessment of the proportion of cases due to asbestos requires careful expo sure ascertainment methods. This point was made very clearly by Cochrane and Webster (1978], who noted that "a history of exposure to asbestos can be established in a sig nificant number of cases if histories are taken from the patient and recorded by a medical specialist with experience in the field of occupational medicine." [n their own study, histories were taken from patients by one or other of the authors, usually by both. Where confirmation of exposure to asbestos was necessary, it was obtained from executive and government sources. All interviews were repeated at least once. These authors reported asbestos exposure in all but one of the 70 cases, and the one exception was a carpenter who claimed he had "worked with asbestos sheeting only very occasionally, and although he had always kept asbestos filling for screw holes on his workbench, he did not feel that this, or any other exposure, had been meaningful" [Coch rane and Webster. 1978]. ' Another early study with carefully obtained work his tories found that 35% of 246 cases could be linked to as bestos exposure [Greenberg and Davies. 1974). Living sub jects were interviewed where possible. Occupational histories were also sought from coroners and from former employers and workmates. The final classification was made by two medical advisors in consultation. If one fo cuses attention solely on those epidemiological studies which have obtained careful work histories, then it is clear that the large majority of mesotheliomas in adult males are attributable to asbestos exposure. Since additional cases may occur from unknown occupational exposures, it is likely that at least 80% of pleural mesothelioma cases in adult males are attributable to asbestos exposure. That a large proportion is due to asbestos is also consistent with the evidence that the rate of mesothelioma prior to the 1930s was extremely low in the United States and in Europe [Mark and Yokio. 19911. Production and Use of Asbestos in the U.S. Chrysotile represents approximately 95% of the total world production of all forms of asbestos, with Canada its largest producer [Mancuso. I988|. Amosite and crocidolite accounted for only 5% of the asbestos usage in the U.S. over the years (Table VI) (Minerals Yearbook. 1926-1950). For example, the percent amphibole usage ranged from < I % in 1935 to a peak of <5.9% (<26.12! tons amchiboles/ 445,902 tons total asbestos consumed) in 1943. then de creased to less than 2% by 1950. During this period the U.S. depended mainly on Canada for its supply of nonspinning (short chrysotile) fiber and upon South Africa. Canada, and Russia for nearly all of its spinning (long chrysotile and amphibole) asbestos. The U.S. produced only small amounts of both chrysotile and ampniooles. Chrysotile had a wide variety of uses in the Lf.S. during the 1935-1945 period. The higher grade, long fibers were used in woven brake linings, textiles, and sheet packing. Lower grade, short fibers were used in asbestos shingles, paper, molded brake linings, fireproofing, floor tiles, etc. Rhodesian chrysotile was used for electric insulation, gas kets. and flameproof navy cable construction. Chrysotile was also used extensively in heat insulation (Minerals Year book. 1936-1950]. During the war years, amphiboles had specialized uses in the U.S. Amosite was used for insulation around steam machinery on warships, special pipe coverings, and block insulation. Crocidolite was used for asbestos-cement pres sure pipes, chemical filters, acid-resistant packings, and gas masks (Minerals Yearbook. 1936-1950]. ' CONCLUSION CONCERNING THE CONTRIBUTION OF CHRYSOTILE ASBESTOS TO MESOTHELIOMA INCIDENCE The three points made above can be summarized as follows; (1) chrysotile asbestos is a potent cause of pleural mesothelioma; (2) the large majority of mesothelioma is attributable to asbestos exposure; and (3) chrysotile asbestos has been the major fiber type used. Based on this evidence, we conclude that chrysotile asbestos is by far the main contributor to pleural mesothelioma causation in the U.S. and other countries in which it has been the predominant fiber type. Srocidblife'may'bSSi^^Tmes more'`pocent. but there+is7no'Valfd`"endirice"thagaihosice is mdre'pbteht tfian chrysotile; Even considering an extreme that crocidolite and amosite were 10 times more potent than chrysotile. the ex tent of use of chrysotile means that it would still be the main contributor to pleural mesothelioma causation. ACKNOWLEDGMENTS Support for this work was provided by the Health Ef fects component of the University of California Toxic Sub stances Research and Teaching Program, and by grant 93E0023 from, (he California Environmental Protection Agency Interagency Agreement. Additional support came. Cirysocile Asbestos and Mesothelioma 263 TABLE V!. Estimated Quantities ol Asbestos (Short Tons) Imported or Consumed in the United Slates' Tear Canadian chrysotiie imported* U.S. chrysotiie produced African amphiboles imparted* U.S. amphiboles produced Total consumed in U.S.* 1935 1936 1937 1939 1940 1941 1942 1943 1944 1945 1946 1949 1950 154.200 226.080 276.002 223.840 225.553 389.391 336.547 385.655 353.228 355.768 442.073 470.783 678.353 NA* 10.520 13.284 14.686 17.481 20.144 13.109 3.900 6.296 13.340 4,438 NA NA 945 2.080 4.247 6.359 8.752 21.447 20.424 24.007 19.162 13.247 6.324 22.720 14.805 NA 404 612 450 1.693 2.252 2.206 2.114 317 250 437 NA NA 174.655 250.922 316.260 255.547 262.199 . 438.741 434.121 445.902 407.148 377,875 459.752 535.132 728.785 'Oita (or year* 193S-I950 obtained Irom mi Minerals Year 8ook (1936-1950). includes crude and milled fibers, as wed as "stucco and refuse.* sMay indude some small amount of African Chrysolite. 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