Document XzLZY4gzqgmJkm4ByGEQ1Dxny

Er RajfH'rJ. 199)5.9, iSail-i'.}.-.;.1 friwoa ft uk > jjB'iigiae^rojwvoa.- ` . " - issN^wsgiaae:^'" -' <p :; !| REVIEW Ifee epidemiology of mesothelioma in historlcal context J.ij& A.D. McDonald the tpitknudogyaf'mesathdlama inhisfoileulsansexs. J.C AlfDorMttf, AfoSMtjjjfamfjL, maJournalstAfjwa. ", ;............ . ..... : ABSTRACT: Pripiur>' nmiignant rocsotiwillat tmaoure were recognized by pathol ogists before asbestlfann minerals (ehrySolili;, erocidolite and nmosile) were mined eomjiJErdnUy, The discovery, 40 yrs ago, of a causa! link with crocidolite and the Wulc-ranging epidemiological studies which followed are the subject of this review. Early caseHCOntrel uiKi deserip Live surveys, supplemented by cohort studies Ui insulation workers- and. elirysolif* miners, quickly demonstrated awjor occupation al and geographical differences, with high risk in tnsvol dockyard areas and in the heating trades-In the 1980s, relfobk cohtwt surveys showed that in minlngandin the manufacture of asbestos products the rne&othcliunui risk was much higher when exposure included crOcidolite or aatOMUi "tiiiui. chrysodie alone. However, qmilita- live and quntiWiw. infanoathm on exposurewas too often inatte<iufllc for tilts evi dence do be conclusive. Well-controlled .lung fibre analyses hate t educed these deficiencies and demprureafed' fbe pnj.babfcimplications.of the greater bfopepsisi . leiica of amphibofc fibr^.-lodCK^mfi-iucsediiibestt cotiiauisifow ooiteau* :t.ridiojis:igif fibrous iremoliitywhichftisy vrelhexplain the few eases of inmtitetibnia. associafcdwith this typcof'AslH-stos, . .... ., :Progi-^s'lia :ttils Gw:ims;iheeii:tiiu'elt retarded hy cumrorersyi; for which -ttft 20 year'^j>'ltil^eehi:^;ayaitabi!iLy.df reliable estimates of risk for the mining-'tif chrv^iile add tliatlfotTcdociddiitc or atnpsite- mayteve bteeo largely r^kfositile; Dept uf Orciipatscnd and lmvitonmeutal Mcdituisi, National if*eh & Long institute, tmperial Collif.c,Jjsttcioft tf}C Cotmtpof^eiwreJf^MeOdfiyd:. .. Dc|it of Occupational sod .Enticorinfewaf Medicine- .. . -iNa&tinai Matt-k Liaiginrikiste b&pstkd: College . CsBsdos , ok... K^yvrtijstsr-Aatpljilxjles lii^euisSWtice' ctuysoisie .lui^'iuialysci ntisotlieiiam.'s trednjliie . KeeCived; Mdirit J5 1955 , ,, . Areepsed after visia htsy 3' t'jwS A m1 ituhisiry, a new disease Asbestos, (lie ".magic mineral", was known to slie rujcisrd Egypthdisand mentioned byPliny, but onlymlhedand manufactured in,.stay quamiiy sihsc about tll$ 1890s. Ai ifthitiroe* exploitation of large deposits of white asbestos (dsrysoiilejm-^ansatla and Russia amfblue asbestos ifecodlMite)Jrt 'Sputh; Africa began tdidEvclop rapidly, iflv ib!thiSf;.ccrtUftyj,-:a:ii)fow'r! asbestos, named anictsitc after tits viIlageof Amosa mci the eooipanytvhtch discovefed it, togetliei* deposits of ehi^oBteMvere Pise mined in::Sbuth Africa. CroeidoHie was,tatef,.found;.atid mitieti iti WAsterfi Australia After lba':sccond^^ world war- aiiddti Ic^cr amounts clsuwhofc. Primaty niulignluit pleural 'mmours.'havd' been: recog nized at least since 1B7& wiish :W_dbfit -OJ:.published .a 'idjiotfon a case oF"tufedc-lfc"'J!yiiSplia^hoina df:(|ie jileure. In 1943, SAcqpN^: ared: :4^atEH2 ^^iV' ifi: s ,,rt;'ol4iNV' . of cases published before 1940, refcirod to iiic tumour as an "etidotbdioma", sad mentioned a rejion by Lieuiaud in 1767 of two svtch tumours in a scries of 3,000 atuap> sics. They went-on lo'.say.dtat-, : our's cxisiwtcc spread, reports appCHtred with increasing frequency. Thcse'autiirix| f tyi I;i eases:;.|jni..3sc;ipbii .set: iW- published: betsveen '19l0; and 1938:in .a xoial of some1 46.000 netcipSLes (0.99j). and iiddiii two coses of tttcir own among 1,000' autopsies. The nwtie to female ratio Q,ta'al| :,,wits 1J, with 50% of subjects ,'agtid . 40-yre of more, SApKjitffi'andiGitiau^ [2J distu^edfls:cprtfusiptt which existed bverjfatholbgy due. In their opiflion; to the tumour's fiirity and lack ofeiiD.racteristic histobgy. From descrip tions and plioioriiicrogsriplis of die 41 coses rnecitirmed, they concluded that softie at .least were of other disc^es. such as brotidiogcriic tarcirioma. In view bf'dsytdgfag opinions at. tliat time op'the origin of c&iis Imtytg ^ripuiB epyiits;fTbm wh1^&e'lusrurn%3'ihn'edii ed tliat ihc iiariie f!plerQ!na,,n te usetl. l-aier, however,- the tend M03esothliohta" 'btM:2mc 'tnore gehemlly ^dpted. 77re linkwtf/i-ai^tesrpy .TJtb'Suggi^tiphlthdf mesothdtoma .rcsphdd-frotirpcca*. jKitionai cxiKisute to asbestos Avas nrst ftvadc;by <iijt>vnTi I3J, inBritairiinlOBS.IftGerriiany,, WcoLFJt/J4j.described two r.3jes'in mcn with 'pslsest.dsts arid V/tass fSl one case in a: naval dockyard worker. Leicm-H [6] was ihe: first to repon a case/ol' periioneal inesflihHlioma. in a texille spinner,: At etMtupific meeting in 1932, Gap,tie3! .f7 j, thfn iftdd(i3i|d dr tile iiidastrini niedical .dinic :at 'llictford - Mines; Quclxib. Qinada, reponed eiplvl casi^ of reSpmi- torv cancer, two of which he described as pleural turn- dues. in . hts. opinion, uvo such ram cancers in a small series of only cigiu casts suggested an occupational ori gin, /, report in i960 by Waomfa ! ai. fK] of 33 cases of tticsothdiotnaniaiftlyfrom tiiccfoddolhe-miniugarca in the ootth wtst Cape Pfovinee pf South Africa: put die pswialion.bisy^ttd: rettsomsbic doubt; Of the 33 cases- 2S.jit'diPP;tn p^tspns wiip hiitl Woifced in flic mir^i w. hv- cd::clpse ,tb ditldf Tlie pstJiplt)gieiil,:materiitl nvailafilp ;* iltphedito thoradc contents; tied peHtonciiJ fumours were not seeit. . A jiflr iqi'. '-'(* CPTOKMfOtQOV ClFM530'tHP.iA014A I3? Tabla t. - Early: eaaa^ontiol Btudta&iOl1 mo^halfemdi gK^g^afinKe ior.pfQbabia: occupational oxpoaoro tg asbestos aodior -. _ ' ' fRet] Place : Years iSp&f Male A Siagnffifett';... . . ^controls. : % exposed % Sihis Up.wuouse :McE't,v3r ' McOo>wtn Ittratso ASHCKOfT Hais Zimnns 1965 1965 1970 1970 1972 1924 1975 001 Mil [12] cm III: .[15; 117] Ifelfast, UK J^tcdon, UR Scotland. UK taaiada Pfedmcnt, Italy Tyneside,. UK Hamburg, Germany The ffcdterlands 195CW964 1917-1964 1950-1967 1,960-1*168 1960-1970 1948-1967 1958-1963 1949-1971 42M2. 95 76 ' W& 49 41 m 5S 65 21 ;so?io 44; 12 imm. ` as; 93 W 5S 67/67 94; 72 3.6 :3.9 47. 7.0 6.0 2.3 63 4-0 ' fer teWvorisk; [Sifij: ^rer^tc: nurnber. AtacohFi^oceon.dio^ Efl^tsofAsbestas", a study by die Sdikoff group of New York and New Jersey members of the International Association of Insu lators and Asbestos Workers was a key event [9], Of 632 males at work in 1942,253 had died by 1962, tltrce from pleural mesothelioma, and by 1954. 10 of 307 deaths were From mesothelioma -four pleural and six peritoneal. Two important case-control studies were also presented at tins conference mid litter published (table 1). In the first.of tbesii. 42 cases ofra^ sdiiieiioriia and42 controls In Belfast, UK, tuatclted.for d^te, sex and age. Occupational histories:-wens obtained front, titb living andTronvrblati ves of those:who had; disci. OTtiiej! six:cases hat) a history of occupational .exposure m &sbesfps, mainly in Shipyards, conJiared .wit|!,iiihe.cQa- itoisi The second study was by Ngwkwse andThbMPSOfi fl:l| of 83 patients with cric-sothclioniii dingnoscd rut a- hospital close to. ihd iatge .Cape Asbestos fhdtpry indie easf end of London, UK, which tad opened in 1913. The bontrolseri&rfeHppri^ with other diseases, matched for sex and age. Theauthors acknow ledged that neither these nor fhe irttetview inethods were ideal But concluded that die case-eoittrol comparisons of occupational am) ttridendal .histories were probably val id. Of 7<ipairs, IS- ca,scs {24%) had beeis.eniploycd at & 1%) as insulators orlasers; compared. witltcine(1%) and four (S%) controls, respec tively. A further nine cases (12%) were in pifepds who had lived in die same house as an asbestos worker and were indirectly exposed, comparedwiih one control.(1%). Only erocidolitcwa5iisedintliefactor)'until 1926, when small .quantities: of diryroulc and aroosite were intnsdu- ccd. 1 l|i*: ,t'a$^:conteireettre, a WoridhgQrouj) under die auspicesi of die international Union against Ciincm-f (U1CC) reviewed the papers which Had- Been -presented and made a series of rccomtiiendations, with considerable emphasis on: the need for more extensive cpidennatogicalsuidtes of mesothelioma aiid on tlic impdtiaiacc of asbestps fibre type [18]. As Fihrcbf more than qiteiypeof asbestos was almost always Used in manufacture it was suggested that research should con centrate on countries where it was mined or milled as tine problem might then be less serious. Initially, this ap proach .was taken only in die extensive dirysodle mines and mitls of Quebec, Canada, and in the sma]|cr'i3bi|^i'-.: tile industry. of nonhcmltaly.Starting ia 1966, all36-000 . currcnt &nd .previous employees of the Quebec-itiKhistry who had worked for at feast one calendar mouth were listed, la addition to comprehensive studies of respirerofV morbidity [19], mortality was inVestigated in a cohort of some 12,000 workers, bora 1891-1920. Among 2,413 male dcariis in the cohort to die end of 1966, there was a modest, exposure-related excess ofiung cancer but only three deaths were from mesothelioma. [20].' This prompted the need tor studies of mesothelioma on a wider geo- graphical scale. Almost 20 years passed before comparable suidies were made in the production of crodddite or amosife in South Africa 'and Australia, with a resiitring controversy..which will be. discussed-at the end of this review, Wideni tig ;^c epidemiological net Cm&gmtrtit studies ' f`romthc cnddflSW,.^ (over 400) were a^roached fatal 1-ease Of-primary midignam m^othcliai;;tumour diagnos-; edit, autopsy or..biopsy iu^,' in, I972i the-sUrvCy was ex-' tended to. all- pathologists (almost 7,000.) tlirouglioul the USA. On each occasion, a respo^c-'-'ViSis)bblaJoed from nearly alt of them [21], The patholp^stsAyere Uteit vis ited to discuss the diagnoses and to. collect report?- and material for panel review; Aconuulwitfr metastatic lung disease nom a primary tUEtiour ouLdtle the chest; marched for date, sox and age was selected from die same pathol ogy file as the case. Relatives were interviewed, gener ally by a public health nurse ignorant of the casc/eonlxof Status; -arid detailed- nisitlendal and occupationai histo- ties reebnied. Jobs were coded blind; using & list.classi fied 'by four different expert groups according to the probability of asbestos exposure, Of 344 male eases of rnesotlielibrata,. 188 (55%) corn* pared with 78 (23$r) controls fell into one of the five defined exposaregroups, presented in table 2. Insulation work - on infrequent occupation in contrbls - showed the highest relative risk (46.1). Asbestos prcxJucdon and:man- ufacturc was ncxi in relative risk (6.1), almost wlwlly due to factor)' work. Employment in beating trades, ship yards and construction, after excluding insulation work, gave a lower combined risk (3-4). Occupational expo sure to asbestos was recorded in only two of 162 female cases and no centred, lu three female cases and one con- (roi. exposurc hod been in the home to Uie cknJiing of 8 chrysbtile production worker and in five cases artd onc i 1 R i f* 1 |m| ? ? 1 ' ; , i | l * i f] *' wV-jet. I'M 193-5 I. MdKJNAliOiVft'ib; M<S>ONAU} Tables. :Caise-cotf9!:Sltic?yof3^^ nant nics<i(heiiiat.5ii5MoS'pleot8 and pertoc^iJrt>;,Gaciajfii. J9SO-1;.li?2 [211 " ` ' ;\ Occu(jatjnal^Mp^y|3t4cFiiiitc:;:- --pises Controls or probable asbestos exjpffiSaft irt'=,3445 (n344) A Insulation . ' B Asbestos production t. iiianisfKCiuni fexci, A) -Muling and milling Mwtttfocture: C H(iog trades fexcl, A, B) 0 Shipyards (cxcL A. B, Q' n Construction (cjurJ, A, 8, C,0) . V Giiic ^esd- A, :&,.p!;0ii -B); C< None' ' - - n 25 4 21 70 21 35 m55i i 7 i 5 27 13 M m !76 . ^ <5.1 <1 4 2,8 26 10 UQ RRSi-relaih-criidu-exet;: excluding control to that of an employee engaged in insulation air manufacture. Neighbourhood exposure was investigated by comparing Ute number of cases and controls who had lived within 20 mites#?. s c&t^sotik mine, excluding those occupationally drttend&feally exposed. Mo ease with meso-Lhcliprrta. but. two ctmlruis had lived wiihin 20 miles of a ehrj^otiie- mm InQuebec, Canada, and oue case-and' two" cimtrairwi&in^ianiesrbf a minein California, USA. ........................................................ ..Boxfesr evidence. of an tefeafed riskirt sbipy0itecte fwf pl^:id other: esiscreSiii^b^pd^ published, in the. 1970s- (rafale:. 1). Except for; ihc repOH from northern -Italy, wdt&e, litost of tfe' occupationa] ex posures wejatfia or near' Turin,- shipyard exposures were mainly to ' Auniyxes of ititfidence and mortality Ip the Canadian surveys described-.above, diclpnoM incidence forJP60-l966 waf.oji*c-:-.caS--pw-ini|13ioa' per sons - about 1.5 -in males and fb8: in females; however, there, was.-probably under-reptwli^-during- these early years, In I9$&^li>72, the.incidence..in:Gscfsdo was 2.9 per (RtlUdit .mate arid 114 per'imlUbh --ftttaate; and -in the USA in 1072. the corresponding rates were 2,7 and 0.8 per million. Cases in which a biopsy or autopsy speci men could be obtained were later reviewed by die Cana dian and American mesothelioma panels of pathologists on it probability settle, first on histology, and dies with clinical hut not occupational information. In Canada, the incidence in Quebec was higher than Unit in Ontario, but fewer Quebec cases were accepted by die panel than for Ontario, and the coirecrea Incidence-in the two. * provinces was similar. These estimates were used 3ft 1975 in a geograptiica! analysis of ah known cases of mesothe lioma worldwide in areas where reported cases could be linked to population estimates. By applying age- and sexspeciftc rates Tound in Canada, the number of mesothe liomas expected on this basis was compared with (be number observed. High ratios were found in many European .shipyard cities, notably Walchcrcn, The Netherlands (03), WilheS nishavert, Germany; (21.5) and Plymouth, UK (14,3), .In two: locations wiih largc tLsbestos matte facturingiddustrics, there wwealsohifihratios: Dresden; Jersey, .USA (25.5) [22], It was evident that, even in the early 1970s, mcsotlfcSfoma mortality in North America, was ahuitdy two or thf ee times higher in males than females. This partem be came apparent In nmst industrialized countries and was followed by it steady upward trend in male mortality, which still continues. The implications of life much lower, annual increase in females will be mentioned In a later section as evidence on the question of noooceupational asisesfes exposure. Hiestetep rise in mate, which prob ably began in die 1940s, is well explained as reOectiiig a parailel increase tu die,industrial use of-asbestos,,front about 1910, having .taken accouig of ? 30-^411 year latency [23]. As a result of this increase, oteoihOfioma is curren tly rcsjTOnsibfeforSomelOdiaths'permiliionnialepopulation tn Western Europe and North America compared with an estimated i to. 2, 30-40 yTs ogo, fit early stud ies, only a minority of hutle. cases were.atiribotebte to occupational exposure to asbestos, whereas, depending on location, up to 90% now arc. As the epidemic has evolved in the UK, the overall distribution of occupations whichhave beeii respoaribfc has remained much the same but there is evidence tltat tfes contribution of work In shipyard:; has fallen but has increased, hv-construction [24]. How long the mesotho; lidina:;iepidkijc can be expected to ter is sm important but difficult question, Estimated Crudely front the indus:uial use of asbestos, ib-s^utef possible that the peak might, be rc.ichB itt rtbotit iyek 2000; -falling thereafter over St period of about 40 yrs f23]. Results of a recent . and more sophisticated analysis of UK data are less opticnistic ami suggest that the peak may noi be reached, until 2010-2020 125]. if true, this would point to the greatly increased importation of nmositc for construc tion use in the UK during the 1950s anti 1970s, However, Wi- pjpj^ions mc.highly dependent on the extent to which tttebtheliotiia is fedtfer diagrioifed and ednow than it used to be. Other coma! agents Sip-20 yrs after die piofjtxkring;worii of WAomift e/ fit' [8] in South Africa, a discovery in some ways more dramatic was made by Baris i*r aL [2b] itt Turkey. In some small villages in a circumscribed volcanicarea of central Cappadocia, an extiaordinstrUy high mortality from mesothelioma was observed in die Ideal popula tion, In Karain, a village of 575 Inhabitants, in a 5 year period, 197&-L974,24 from a total of 55 deadis wcreaUflbutel tb jrfoura! metsolbelidiRiL. In Tuskoy, a larger village, both pleuraI and peritoneal tumours were in toasiderabfe excess. Tlie rocks and soil of tire affected area are ridi in wiolitt: minerals, a common constituent of vol canic tuffr Eribnite, a specific zeolite, was found in fibrous form in soil and rack samples -and in respirable coticenimriom in both villages. Experimentally, these fibres arc highly carcinogenic and readily produce raesofheUai tum ours in mis and mice [27], Thc cptemiologieal Itivcstlga* tierns, although mainly descriptive naber than analytical, teste liwlb doubt that these fibres are tlie cause of this unparatl#14d incideiice of (unioufs in man [27], Deposits of fibrous eritmite are common in many areas of the world but to date flicrdlsmo certain evidence, Other ilian in Ttefcey, of an association with nwsotlielibma. :g=: c f t'l 'O faTM -4i /&$ <, Ui'IDCMlOUIGY OF KlESOTHgUOiMA ISIS' Jit a report from hidiu. tl we caws of malignant mesulheiioma were reported in sugarcane workers, with the. sug gestion that organic fibres might have teen tire cause [28], Sonic support was obtained front Louisiana, USA, where two cases of mesothelioma were observed i msimi* jar citeumstaccs J25f- fn an electron microscopic study of ashed sugar cane leaf, silicon was found deposited along the bypoderni resulting in fibres 0J5 pin in diam eter and 10-100 pm in length, lire possibility that such "biogenic silica" fibres might be causally related to the tumour awaits Further epidemiological study. That riKsollwlioma might occur in workers exposed {oniau-madeniioei,illil>restMMMFs3'rVasinvestigated in three large* cohorts totalling some 41,185 workets employed in their manufacture in Europe and North Amcrica. Ofily four deaths were osciibcd to the diseasein a total of 7,862 deaths from all causes, one in a matt also exposed to amtsiic [30}. Exposure levels in MMMF rnaiiufacttireareextrenwlyiow>.iibwcver. Systematic cohort mottaiity studles The i9S0s saw iite publication of resuits from a con siderable number ofeoliort .studies- .in ;spcsn.ilci;dmtpa- tionai groups,''Milcltdifercciwlfniia^riafprocess aniiirt type of asbestos fibre to which the workers went exposed. The main and most recent findings from the more impor tant Of tliese investigations, classified by predominant industry, are summarized in three tables; mining and milling intable 3;fnanufHcture of asbestosfccnvjttt. prod ucts, asbestos textiles and asbestos friction products in tabic 4; and njtscciiauccus indusuiu! groups in table .5. in a few of tltcse studies, attempts, were made to* esti mate exposure in terms of intensity and duration but in none could the level of exposure to individual fibre type? be reliably, assessed; Afirungondnit/h/tg * The large cohort of chrysotiie miners and millers in Quebec, Canada, first reported in 1971 has been followed ever since with updated resultspublished periodically, the most recent in 1503 [311- By this time, almost 80% of the coEwrt had died and the youngest survivors were in Lheir mid 70s. From a total of over 8,000 deaths, 38 were probably due to mesothelioma - all pleural with one possible exception - a proportional mortal tty' ofjust under 0.5&. A cohort of approximately one tenth the sire, front BaJangero in northern Italy gave similar results. No comparable data on amphitafc miners were available Tai#i3. - Cohort rstudies of male asbesti rtilters' fW author .Year Gouhtry Subjects n -.All" causes .% - Dcalfe; l.ur.fi cancer -to;-. Ptifetinhant: ,:l MesigJicHflrnn fibre it. -TSjRjlOOO KcDosald W3 [311 Canada Pkxwtto 1# [32] Ittlv SLMS-'CKfJ4K?. 1042 [331 RSA (1) (2) AHMSWCUSS 1988 E34J Alisiifllia McDOfroj} m&_ (35) USA 109 IS 952. 32t2 3433 6305. 406 2312 427 '648 423 820 165 67 45 ?D12 13 41 545 ` 22 26 37 si 2i fjj: 1.H 2 03 im 2.45 33 4;s " ' Cltrysiwle. 2: 47 `Chrysolite- 4 6.2 Amdslifi-: "20- 473 finwltfi&'te 32 392; Crocktolile 4 14,2-. .TrtMTJpiite '*! inctadmg veonteciite miner;nexposed to fibrous treiaoUtc: [Kef.}: reference <juti!faef| SMRiistandardized mortality rauhf'MK: proportional rnortaBty* rate', ' Table 4. - Cotton[mortatitj> studies of' mate-workers in asbsstpsmlahdfa'cittftns JndOsiKesr First author Tear [Ref4 Country Subject* n All causes . 0 %. Death; LiirtgCaheer ; Itets^ioma n SMR ; Amphibole moment - . TltiJMAS 1985 Gwfeitticf. 1986 Huewas FtNK&STSK 1984 AWkS-FAtW t9s5 Hughes1 19^6 . ;MxosXrn 4982 ` RaRII 1989 Antm 1990 hSeytsEtuisit. 1990 -X Mabofeito- 1983 Titax&rr ' 1994 McDojmld 1983 Poo . 1985 Fricttouprodads Mct3bAU5 1^4 NuwuOVSSK " 1989 [361 137) [38| 1391 ,140), [4f|. [39) [421-: [43] [44] (45] [46) ` [47] mi 1491 [50) [5tl UK Sweden UK USA (plant 1) Canada feattec1.. . USA (plant 2f Italy Denmark Sweden Austria USA USA USA-: UK USA UK Far ddinhicRS se legend to Table 3;;. 1592 ii76: 1510 2565 535 ISIS 4366 260s 7996 1929 2816 1543 1247'. 4137 3211 3641. 9104 351 32' 230 19 334 .35 477- 19. 108 20 206 W 874 -20-' . 728 1305' id 'S9i '540* 19 570 n: 607 W 895 '22. 727 p 803 22 2035 23 24 1135 - 48 26 9 107 lit); 162 35 50; am :tp 0.92 i,17 im 1.63 1.44 2168 im 2;50 1.72 2 -- 0 k 1 2 19 4 4 8 28 ' 13 )3'- ' "%-i -U20.7 59- io 72 2.25 53: 1.05 93 1.44 : ,i 1 .^14 'J' ,rd ?5 ' 1-1.8 73 1.49 229 1.03 a0 u &4; Ntinimal KubMnntial * Minimal Substandal Miniiu.4 ijijetitfeei) ip Ii r::\ i.:;; |v 1 fbhe iE|i I M pi' l 11 iSiffii^^iSaSSSS;, i9:tf. JXv. >ij3JQMAtO,. A.;,' McDONAkn L mdriaSly- stiidtb^' *Of. riwid 'ibid "fehtafe ashiSStoSrO)(jjdi#3^pters- i:n:miGC idiisttioi; . .aatitar Ystar. IKef-I &>urtry Sub)CC5> AJIcatistSs: H %. tkaills -. , Limp cancer n Predonistu'int 14esotbelionw : n (Use J.usulariuftwork Canada ireuludonpi'dducts isianufa^tiu-c SaoMAw vgasi: usa .-Atedsasr .1984 15*4} uK: Filter assembly '. McDonaio- 197S (5^ Cisnatla- Joses 1980 156} .bJK:: Tausoit AausQs 1989 IS7I USA isii PSI UK# UK:(% 22TI: U unclear1 :4$#; I^i toas 33 mu :m 52S 233 6 Sd Mi Idd 13 28 85 219 -2T 177 31 397 424 76 38 1.31 S: 12 '2'J4 g -15.71 15 2.41 f 1.45 - 175 17.1 Cltrysotifc .48:tuitdlite; 14 25,5 . -Amorite 5 tSM Awojiitc: fl . m.r m ' 174,7 ''S'-.. iis - 5 22,8 1'f ' 5.6 CcwidoUte Croddollte Crocidolite Crocidolius. Cho^oiHe . 1980 1^1;: WKv :li043 17 ' '*$ ot>lis!^K^2.4& crtscidolite. Foe dcfinMonji scfi legiind tq. table 3; 84 &.4 . 29-7. '"Nt)tst3aaii5;i tihtil.'ibe late 19^;: whe(i ;iifedjii|s fQr.crwidoJifes and ' Amoshe were published From Soth A^a aiftd & cr(>oiidalite-frotia Austraijsii'At about l##he';tlfl#sy' twp-#iall .-soharas-of .^Iittiikoltte.imasni in the tl^A,:Ona-of which had experienced substantial exposure to fibrous tremo; !tib; -pfey^fl; itrspprtini- bvldeoisi. bo ,tK:ojSibct$ [35]- In 3, il :shcu'd'te: floted'lhat- the crbCKlolitC:vant;'am'ostte. rates were; derived from cohorts of wr|iie(i only jl.?Ai:t:#. tiie esblbridtiofibs; duysbtjfe vt^htKisi'; di^,|)bno.rt3bt)fl) mortality from tfesptiibiibma: !'Sts::Ieb thart: 2^per; l.OOO. Propooional mortality nites are a very crude Irxiecator of risk. since' fee^ do hot t&e levels of- exposure ;or tsrniipstinf :causes: of d*adv i.nw aceduoi, Nevertheless;, the- data; .iil: table 3'leave tfjtic dobfet Sit .craeidfojUe .carries a much lirg}idr: iifik ihp tduysotildl/'w'Klj 'afnosite 'and' tremolire probably some where to between. ' " ' '' ' processes 1^. i?'cohorts shown tn tdbtd'4 were informative in thutal! were, engaged fit tire manufactureofasbestcis-coulainiog products, predominantly from efij^tijc Imt sdme with die planned inclusion of reiadvdy stnail quaritities pf crocidolite or. artiosife, laterprctation df die rcsiiit<; is facilitated by the fact diat die prpppiddfis d^idt time pf analysts in .each. cohort- weft of the; sdsawf Order, -.all' but one (49%) ranging 14-31% (median 22%). With each of the three types of product, there was a .fairly consistent difference- in the proportional 'rates for "mortality from mesothelioma between cohorts with and without exposure to amphrboles. In cement workers, tire relevant: rates per 1,000 wen*2Q.7 and35, respectively; if* textile workers 14.& end 2,5: and in friction product workers 5:4 and 0. To these admittedly cmds compaH' sotis, iiiatte witltpiit fefeEence to intensity of duration of: exposure, some Limited detail catvbe added. For exampic, the only death in die cohort, of Garokeh et aL {38] was in a map first etnplPyed in the. factaiy less thah' 2 yegirti earlier. In the friction pioducts cohort: ofNkwhousc of the II casts observed; were from a small group of employees who worked for exhort time on especial i'croddolitis contract, and there wiss iio case auributable oniy to chiysptilein thfercinaibtier of the cohort, Mlscdimz^s Although all but one of,.dtp.cohorts;shown'in table;5 were .exposed wholly or largely to amositc of crocido- BtS; lire data are t^eon^^ttglile i itteft'th.lhe verylargo chsiort of. Arttencaii insulation. workers .invsstlgated by ^EUuOFP ti aL pSIis rias of-the classicstudies of asbestos e^&rsibldgjv;At. % stage wlten : ci[y l 3% had died.ai- inost 8% of'deaiiriwcrcauribm^ thirds of which were -peritoneal, Initially, it was. thought lliat thc cxposurc oftLiese svorkccs was mainly to chrysotile but it spurt bectinre..ck`at-tiiatatlcasL,froiril930 onwards, amosite wastbe- predominam type of iisbesiibs used in American insalatitm inamriali'. The suggestion was bride at the johivtintsburg Conferencc: in 1977 dial amorite rather than daysotile ntiebt lie responsible forthe prbbtern i)ui;djt:h|s:dpty; recently^fo^cm::cotrfbjikiI, by itingbtiideti 'analyscs [<51], Two cohorts of workers expos ed only; the ftianufactuiecif insutationncaO- rials, one ilvtfe USA [Sdj tmd the other tn the UK (53], hive provided further evidence ofthe capacity pf thisnutf ernl fibre (O' cause mesothelioma, However,- at face val.oc, their levels of risk did not reach thnt of insulation work ers employed io applying and removing these rtiatwtStsi The.iuglrest- rccordcdptopottioral ntortaii ty. hates iretn mesothelioma were observed, intwo :remtk!#lb:40h<)rts of males and females who wotkeel for quite: riibirtperiods of time during tire early years oi` (he second world war in England and >n Canada- on the installation of filter pads . in military gas-masks. The pads were made from pure crocidotitc believed to have come from tire Wincnootn mine In Australia, where a coltott of miners; and millers -wai; studied - soine years later (tablc -3). An tdentical, pat tern in the incidence ofcascs began both irt England and Canada lS ym after rim exposdh^ and rreddnuire to grew for at least IG morc yenrs; io dic UK, ncw cases are (ail! being seen almost 60 yrs later (I.S.P, Jones, personal cornmtiaieation). The nearest equivalent: to these diste* Woos events was seen in tt small gmup of cmployees in tlieBJanufaciure of fillers forclgtireitts in the USA from* - } 8> it 3 tf y .) 1 3; 4. 1 > O 3 ,T44: l I y l i-; y- JiffDB.MSObtfQY :OP MKSGfjfEWOMjV $&% *r alt things, crocidolite {571. Five cases af mesotheli probable occurrence of mesothelioma as a rate malig oma from a total of 33 deaths (15%) were reported in nancy unrelated to asbestos exposure both before'and that group, . . . .. ... . since ihc industrial use of these fibrous minerals began Finally, a study by Rossmat and Couis {59] of over at ihc end of the last century, Ihc simplest evidence, that 5,000 males employed in die Dtivoaptirt (Plymouth, UfCj cases arc not all due to asbestos fibres is ihe high mor ''L naval,dockyard is worth noting. Asbestos exposures were tality from the disease in certain villages of centra! Turkey. not wd1-decomerited but certainly included no afreet- (0 which reference has already been made- These cases :r able proportion of crocidolite, Tins was not sufficient to were clearly caused by local deposits of fibrous crionitei; produce excess mortality from lung cancer but it result- a mineral with many physical and biological properties edin a, large ntirnberof cases of mesothelioma. similar to crocidolite and trcmolite. Deposits of fibrous erionjie are widespread on the uanh'-s suiface and there &0Mew - t. is, indeed, some suggestion of related cases in proximi ty to deposits in die Rocky - Mountain states of Worth Few, ifany, envirotimental hazards have beets die' object America [63] but not elsewhere. of so many cohort studies as asbestos, only, some of Other suggestive evidence, historical rather than grate which have been mentioned in this review. Aidtough it graphic, has also been mentioned. Jt is fairly clear that f would=be difficult lo conclude from these data-that the capacity of amphibolc fibres, especially crocidelite, to primary malignant tumours of the pleura were recog nized by pathologists at autopsy at fhc end of the last produce mesothelioma is not considerably greater titan centoty, before the industrial-use of asbestos could have V that of chrysotile, uncertainties remain.Thc problem lies been responsible and in. the absence of any link with in the evident complexity of the -causal relationship:; and occupation. Alihough thcse cases werE somewhal rnore '.i. the many factors other than fibre type with which the corrinton in mates- than females, their distribution sug crude Information available on exposure in these cohorts gests cither, a generic aetiology or an cnvirottmental fac- has fluted to: drak Whilst duration of exposure can he lor common to both sexes.The latter could conceivably: ,estimated fairly.accurately, .ilblfc concentrations by size include, waterborne or- .airborne- fibres originating- From .a^3,tyj^, p^inp.t, ThiS'-is a. serous, problem when expo*.. ; a Wide range-pf-rimunilly tc9ti^,^n^'.^.tju(- sbriteare M&fcn: Jo have been romora than one type of rencaoffesotbteUomain.cteldltcxsrileqdstosimilarcoii- asbesios. and: of. increasing ihippihaiste.; where one type elusions, Evidence or such rases was found m three :y is`somstioteS;Cdritamin3fed "by pother;se, for example, Sinvgys, the largcsr ofwhicliby FnAivi- i-r $1 {64] record chfysoiite by trcroolite or ambsitmfcy croddolite, 'Uteris ed 80 cases In childhood, itt only two Ofwhich waters^ is also reasotiito suspect, that tte bacurc of:the industrial posure to asbestos at all likely. Unless the usual latency.. process may affect the outcome, as die textile industry xvHti asbestos-reteied cases is nmch ^wtsiriii childhood, dees forlung cancer but not apparently for mesotlielitStna.: the existence of these cases suggests thal therc-musi have ft is, therefore, hsrdly surprising that, with the exception Steen 'some other cause. . ;. . of tfe studies by Hughes ani-VFau, [39jin th&tfestosf' Less conclusive support for a- background incidbiicc is c cement industry;, there still exist virtually no reliable riant aftordcd.by the risbt&of iti.Bg' bmiipri''-in^ys$(':)ii three On exposure-response for raesolh'dlyma WblptrMkcgtx:- c^sc^o.atrolstudics IpToilh.Aisffirica-and: the UK, which. c outtt of any of.these varinbles.Tbavotd Uwpfobfcins of are'.described rodreFullym the new section. Inallihrse, environmental-.exposure assessment monirecent epide a propoition of cates could: not- be attributed either to miological researcli has turned increasingly to-the rise of anipiubote orChrysotite fibres; However, ihe snrall nujii- : lung fibre burdeo rncasursntefUS- Tlusapprmdi and im ber of-rases: exarhtnl;ar)d- die limits; pf-^jrc-dcriectipn portant new- insights into the discasc potential Of chryso by electron microscopy reduce the confidence dm can ... lite rut discussed in a iater iecrion. bfi.pmon- negarivcifindings,. : ", .Morerobustepideiniological evjdcocb is given by mor Nonoccuputional mesothelioma tality statistics fof nicspthcIiQmaovttr ilje past 50 yrc or so. In most industrialized countries, lire disease has incr It is clear enough that hi most cases of mesothelioma,, particularly in jn&usfrialisted countries, there is a fairly definite'testp^ of dtreccca-indirect exposure to asbestos; tttwork, This bas led many to suggest that all eases may b<usd in this way. Ttfjs hypothesis raises two sepa rate Ructions: firstly, is there: evidence of a background incidence of thedtseate before, and presumably also since, : asbestos was first exploited, for industrial use? and, sec-! bndiy, are there some cases attributable to asbcstos btsl resulting from exposure in flic domestic, ncigiibouriiood or general cnvironment rathef lJi<tiv at wofl;? TTicse two aspects will be considered in turn. eased much more rapidly in males than females, reflect-? jng die impact of occupational asbestos exposure 30-40 ,, yrs earlier. Backward extrapolation of these trends sug gests dial,, before the diverging pattern began, mortality was about 1-2 per miUlqji^ajJtitptm in both sexes. This conclusion is supported by data. from couistiicS or regi ons witii tew mesothelioma mortality, where both male and female-rates are.ai about this level; and by datafor California, USA after exclusion of occupationally rc- IfttedcaststdS], : ff indeed there always has been a low'hackground inci dence of fttaligjtant mCKoihclial tumours unrelated to the industrial exploitation of asbestos, there remains die ques tion of its aedology. There are no indications that asbestos Tiie baskgrcimdhypothcsis a k occurs naturally hiss been responsible, although tills possibility would bcdifficult to refute. Similarly, nlthougii In a recetit rcvrcw o.f this qu&sriou [62], five types of tltcrie are widespread deposits of olher fibrous minerals; evidence weire exiujuiicd, all of which printed to: the such as eriociite and tremolite, wbich could conceivably Cause sporadic disease, there is very litlle evidence trial they do. In special circumstances, however, where local rock has Wen used for domestic whitewash, as. io New Caledonia and several Mediterranean countries (<K6SJ. exposure la fibrous iremoliie from diildhuftd may well have led to asubsUiminl number of! cases, A num ber of oihcr agcnLs, such as biogenic silica fibre from buroed-off sugar cane, some heavy metals (especially beryllium) and iodizing radiation have also been cited but none, eon firmed. Nefgftltouthaod and rlomcstic exposure Hie question, thus comes down us whether flte Indus trial use of asbestos - amphibole fibres in particular - tin lead to sufficient environmental pollution outside the workplace 1o cause nonoccupational cases, . It is: fairly clear that such cases do occur, but rarely, Tlie evidence is strongest lit cases presumably resulting from domes tic exposure among tits household contacts of asbestos workers. Such cases were documented In several papers mentioned by Card?* and Saracci 169) in a recent review, in most of which croeidotiic was probably res ponsible. The occurrence of neighbourhood esses has also, been described in the immediate vlcinlry of croci- Ilfilite .imises in South-Africa and Australia J69t, Odd of Factories which ustd. these fibres in London, UK, uiul Hamburg, Germany, (11. 16], Most otherstudies of neigit* boirmood cxposurc havc been negative. ; Moredifficult to of mcsothclionia inay arisaasa result ofgeneralurban 'sk< pollution with j' riinipst rill chrysolite and usually very short - id .industrial cities of North America .and'Western Europe. Thereislitllc or no: direct evtdeitea; one way or another fof iliis hypothetical -risk. Tliat it Is probably smalT and: ilniu& certainly, beyond Ute limits Of datectiOftis suggissiM'bo^'by. letqpiisure- 'respqn$e;.findms in .by.-tlta^el dial uioilsilty in females imNoah AriiCfica arid WeStfera Europe has shown little or rio increase dur- mgdjeiast 20-30 vrs, The latter holds despite the contri bution of occupational and housebold exposure and the greater awareness by physicians and pathologists ofroe- 'rotisetiqriia.duorig the same period J25J. Ming finrden studies Since tlw pioneering work of I^Mctur and Pooutv [70J in die early 1970s. flieusc of analytical transmission ei.pc~ .. 'tfbn.microscopy to identify and quantify mineral fibres '' tn lung tissue has introduced a technique of great poten tial value for epidemiological rcscarch. ln the:assessment of past exposure, its specificity and cumulative capaci ty are far greater Ilian was possihte from work histories and scanty environincniat measurements. On die other hand, this approach is limited in practice by the highly se lected availability of Irmg tissue, and by the varied pen etration. persistence and distribution of mineral fibres in die respiratory tract. Also. the significance of fibres in lung tissue at death is affected by whether or not the dis ease mechanism is related to these same fibre qualifies; It was shown by Poorly [71) and Rowlands St aL I72J `liafll^'aNWi-ltili^MtW tfi&wws in die Ability df chtysotile and umplulwSe fibtes to penetrate and persist in lung tissue. Thus, only studies which arc adequately controlled for .time variables and in other Important respects, and where (lie analyses are conducted blind and in parallel, p, ovidc reliable information, [lie six surveys, listed in tablt 6 are those tn which Hirsts requirements were largely i tet, buteverr so with results which cannot readily be compared or tabulated. Whilst it is evident: . studies.:that nrnphibole fibres over 8quit it) length could have explained nearly all the casts and shorter fibres few if any, there arc seve ral tjrguraetits for arid against the possibility ihri chryso- tilc may also have played some pari, Certttiiily, the power of the multivariate analysis used, by McDonald ct aL JT/J was hot sufficient to negate findings from their uni variate analysis or to imply Incompatibility with the ob servation by Rosens ei aL [7SJ of a chrysorite excess in tile few cases wi'ertt ompbilioles were, absent In die lat ter study, the selection of ail controls front a single hos pital in Sydney, Australia, over a short period of time and the lack of matched pahs threw some doubt on the comparability of die 25 cases and 31 controls witlxuif amphibolies. Mare substantial questions have been raised over die validity of conclusions an the role of chrysolite obtained from, lung analyses at aiiiopsy, Some have argued that Only analyses Of pleural tissue would have..any relevance, perhaps without appreciating that Shc 'lurig is simply be ing used in epidemiology as a sampling device to reflect past airborne exposure and nut adbeet pathologieal eff- ect. Tlic fact-reiriruris that as chrysolite is of low-pcrsist* ence, concentrations found at death may bo unrelated to. what was Inhaled over a lifetime and. indeed,may predo- nupaptly rafteef only .'very, recruit exposure, These ques tions Itaye been reviewed by MetfawALp ;f79}, aiiri iripre fully, by f^iugai80J.4n essetteCs. die validity .pf.lungbbp* den rneastirtUtKJrts ihepjdemtolagy depends on: 1) how well they icorifitate with best esfiniates of past'bxptxsure; and' -2)r wither -the: mviridgalions., were- 'controlled for Ume-relritefiS. ritril. other potentially otmfaufidicjg factors, FpfrieiJiicr of these questions Is iliarifiswisr entirely clear. There is, indeed, evidence front ai faidy small study by Rowlands ei aL (72) and a larger one by StteASW; et at. til] of a reasonably good correlation with past envi ronmental exposure both for chrysolite and for tremolile in miners and milters in Quebec, Canada,, and also in 'American:, textile: workers, but .farther confimiatioi) of - this; kind is needed; On tite more, difficult matter OF ade quate control for confoumlers, even among thfi-sixstudri tes showu in table f; not.one was wholiy:isidIti|fia[o;.)ii - tills regard. itwoul d seem: unreasonabte,. eycrisfil toTtil1 cci entirely (he consteceiu evidence which-.th^ptosCnL The. association of fibrobs iremptitc with rriariy cfiry- sotHe deposits, leading to tow but varying coittaininatktn of tljc final product, was first identified by lung burden analysis in 197<5 [71}, This discovery had two possible and conflicting iraplicatioos: firstly, tltol these aniphibolc fibres' mlglit be disproportionatefy rcspnsible far dis ease apparently due to chtysotilc r. particularly mesothc*... Toma - but, secondly, that as a mucli mow persistent fibre, it might simply serve as a marker of chrysotiic no longer present. Before dismissing chrysolite as a cause of mesodielicmia, iricrcforc, note must be taken of the extent to winch tremolUe Is: found in dungs at autopsy in ^owidt;^#::;^K::s^0iraatibM, ' : i>m faWfe 6, - Ajnaiysjs of rnifiipriti flb^g ia Ittng ttestjo rrofn^ffl^selheltona cases and cortkofo Firift: Year (Rc;f.|i;:CSUntiy -leaser: atiilibr . ". Controls Odds ratio for Evidence on cKiy^SifK' amphlbtiic fibres'! te.-iis. ,4980:: 1731 UK S6 cases sotifSed SC cases (lung cancer.??, 7.4 ..' ChryimiiJe present in 2 by coroners 4 cwebrnwctiliir disease i>f 4' cases without pufltotogtsts, 29k matched for age. sex .snip!)Itrales: 1976 ' MepOfowb 1982. m\ us* & 29 casesfrom Secondary limg cancer; 3,8 - in pairs where niiaA survey of matehed for age. sox, date, , amphfoofo conicht was. .pathologists- awflMsimal <10* fibres-g*1 closely -iimitar distributioni df chtysoiii* < 1985 M gv*cS, county, 25 eases excluding ntaltgnaftt 8.5 ; fibre:type not identified ctiKcr registry, and cltrnmc pulmonary (based on - 1970-1979 disease; nuuchcd for age, sex, all typos of year and residence ampltlbole fibres) OAUOK'-Jar 1.988 < 30 cases fraiit Kantes district, 20 welt ef adenccarmeroii and-Stjutewir cttictitbina, amphibokfibre Similar ctmcenttaiionilfl cohewitretion cases antlcomrols 1480-1952 secondary, lung cancer and 2-3 times % cardiovascular; disease; matclutd for age. sex and higher-that! ill comrols ihospita! . . f 78 cases freitt Nciimalignarii, nonrespiretoiy 6.6 for fiitres Iy0W level riskfo; .v Surrey tjf ' disease; matcltcd for age. sex, S3-pm in univariate aaalyrisjiihcl.:- { pad^id^sts, I988-19S4- due, hospital and typeof , sample . - kst^th none in emitjv3riaiie analysis . Roote' iM t .?$) Australia ISi'case^.ftom 359 tissue saiaptes-fftsui-a;. l6^;fesiiU)res 7: of 25 and 3 of hospital in Sytfliey exuding. SlOuniiit 31 cdtHrolSiWilhoui ' Mitintiligua-pt i^yiteaty!. tol|h: - tepluhole fibres li^i: < 19i)-.Km5: ^aseawec'aiKt-'4A3^ipt^i^'iiia=ar;'. unmatched : ^T-O^ifltKCC-cr^Hctnysa^iS-' fc Rtfo^H'.eivrf: 1781, Bnt:comj)Srisan of casifs-.an.ts- ^nfoil'i-above and; below- l(^..tepfoif this di-iearo, Uglii is thrown on tlifoigifostfouby saver-., ability of chrysdtile (o penetrate ibe smaller airways but al studies, of which (hat by MdOcwuLb ei tiL l?7l, being the major factor was. undoubtedly the, greater durability well-controlled, iiirfiraied that flf 7S esses of jnesortiss- ofthc ami^iiltoleilbriiS.Vvhateverihe cxplanatioftithc pos iionja from across Canada,, pcibaas 29%: wees due to -tiembUfo. An iiiVBsiiaiatibB iitt''(fK!'fJSA by-Roecu ei-al sible importance of persistence in pathogenesis was itn- n.vedimdycvMem. . |S2J,l although without controls iihd tterefbm less^-inter;prethbfo.jo totes of cause- anS:.;efii:t,l(feBM^.trcTnO` ii.te fibresyiti uosiatcd concentration in 5591 i^S^bastSs. .There are various-reasons for riously in relation to mcspUielidtei. Tlie most direct in= dication of the caretoogenie. potency of tehcrijli Ftbres: id Thus,: someoC Lists ttiesoihdiotBa,eyscs apparently -Barite the ircmolite series was seen in the small coltort of 406 utabb to trehipHte may Isivc resulted from hnv-Sevel cpn*- Montana, USA, veimiculite miners anr3-;tlfi jf ` lamination of industrial clnysotifo, for witkirtemolik is not oriy a marker but as shown below,, ruay ttitlced W of which were published in 1986. (table 3). Among only 165 deaths, 21 were from lung cancer (standardized mor the cause. U must also be remembered that Fibrous tremo- tality rate (3MR) 2.45> and four from mesothelioma, i lite is a common contaminant of seven] iitdi^nhity;.'&- {proportional mortality rare (PM R) 24.? per 1,000). At 4 plotted mtiierafs odier riian chrysoiile. a cotiiftarable stage m the-evolution of the thtysodie co- lairt So Qtidtec, Canada, among some 4,000 death! 10 The tremoliie gtiestfon were from mesothelioma (PMR2J.pcr 1,000). The aver age cumulative exposures experienced by the two cote Tbe extoisiva pr^ranime of epidemiological nsseairdv Oris were 145 fibresmlL't-yr: In Montana and over 1,000 in lhe mines and nuns of Quebec, Canada, whfolrbegaii fibrcs-mU'^yp1 iivQuebcc. A vety rough-ealciiiariwrvfauldv 30 yrs ago; was undertaken in the belicF. wrong as it tur ned on C that the results would reflect exposure to pure, tlterdbre, suggest that if about ]% of the Quebec expo sure was .to tremolite, .ibis ampfribote fibre might- expl ehrysotile, Any impurities in,the ore body were conside ain die mesothelioma risk at both locations. At tltat little, 7> red to be of minor importance and unlikely to cause dif ficulties in interpretation, Tbe gtiological data availalde however, there seemed to be-no way in which this1 high ly speculative hypothesis could be tested. Id alone vali tended to support this view. The First indication ifini tite dated* . . -: i ; situation might lie,more complicated was revealed by the Further support for (lie general concept came to light rcstills ofeittCtrCJfi ntiCroscopc analy.'ies of lung-tissue front a fewycafo later in the case-control study bared on lung cx-minc workers reported by Poolev to I97& f?l j and Rowumvss er ah [72] to 19S2, Not only did this show that chrysolite fibres were noi alone but that air jhibolc fibres in the:tremolitc series were also pretJont i ltd. usually < tissue analyses of 78 mesothelioma deaths in Canada, 1980-1984 and matched referents (77]. Owiceimntions . nf amoske, crocidoiitc and tremoliic.but not of ehrysotito or any other identified mineral fibre, discriminated even higher coticesumtidn, In part, this rejected.a.lesser sharply between the two series. The attributable risk T-rertW1' !940 ,J>C.fttp,- A.O. McIXiNAJ.,11 associated with ireiuolite was estimated by multivariate early 1970s Iliat this tyjic of fibre rarely causer! mesothe analysis, suggesting that perhaps 23 of (ho 78 cases were lioma, it was nearly 20 yrs before comparable informati due to iremoiito, including all nine in the Quebec (tun on became available for miners and millers of crocidohte ing region. After excluding these cases, (here remained or iituositc. Jl is understandable that investigators famil 14 of 69 {if., about 20%) in die rest of Canada mtrib- iar with die disastrous experience of insulation workers utalkie to tremolite. Given that in the past ctwadblhe and in North A merica,. thought to have been exposed to amosiit comprised lass than 109a of all asbestos used chrysolite arid, possibly amositc, found it difficulty commercially, it thus appeared possible ttet. Hematite as bJwve that all types of asbestos were not equally harm a contaminanr or chtysotile might explain most of die ful Tnur regrettable conclusion was that the data from , remaining cases, '. Quebec, Canada, were wrong, or worse - & view sup A better opportunity to examine the hypothesis came ported by laboratory experiments which showed that all a few years later when mortality in the Quebec cohort : fibre types were equally carcinogenic for.ra.ts,. . : , was updated [31], By the end of 1988,33 fatal cases of Against 4 background of Suspicion and recrimination, mesothelioma wore identified in a total of 2,300 deaths the results of the several important cohort studies publi: from all causes (PMR 0.45 per LOGO) and by the end of shed in tire 1980s failed to have niuch effect on encrenctred: , 1992,38 cases io a total of Over 8,000 deaths (PMR 0,47 and conflicting views. For those who saw chrysoiile.as * per 1,000). Among the 33 eases aKrertained before 1989, a mineral fibre of low carcinogenicity, die findings .sum 20 were front Thcftbrd Mines, eight from the town of marized in tables 3,4 and 5 confirmed this opinion. Fof Asbestos, and five from a small asbestos products fac those of the other persuasion, no great difficulty was tory tn Asbestos where erocicldhm had also been used. found in maintaining (heir disbelief: the uncertainties Statistical.analysis showed that the mesothelioma inci associated with mixed exposures, lack of information on dence was about 2.5 times greater wnong miners and exposure intensity, aad statistical chance wereoften cited, millers at Thetford Mines than Asbestos 1831- Data on bm less fiattcring-rcilsons were not far below die sur h:ug tissue analyses by S'ebas'hm from our earlier sur face. The aphorism dial "what a man would like to be vey [811. although seamy, showed that tremolite fibre true, that he more readily believes" probably. applied to co ncentrations. were 2-4 times greater fit Thctford Mines bpth'-'sidKS;.: ' . . . i :': than Asbestos (ratio of medians 2.4; ratio of means 33): fiome resolution of this unhelpful controversy came 1831. '.......................... _ ;: wiij) die use oflung tissue annlyseslu epidemiological re- . More demanding: currently being applied : search. Despite difficulties in interpretntion of results and io dic most recsnt cohort daia/focusiitg entirely on die tlieabsolutc ficed forproperlyselected controls [79], these 24 rnasofliciionia casesfronvTfietrord Mines, 22 of which Studies have shown two things and are on tire way to tes :WBTO<|ipS;wtfe ^^sst company in that ting a third, Firstly, thectearevickncc of an ovcrwltclmifig area. Advamage is beifig;tatcen of two important facts:. predominance, withdose-response, pfampluboicfibrcs in firsUy.thauiiis. company bad originally, 'compn'sedtnany hiesotiielioms cases, Second!y, that imphibofe fibres per ' companies distributed over s fairly wide ged- sist iri Itiiig tissue, wb#eas chrysmfifc dtici rie^ftluis, the :^j^dc^|'0ea;:d^:seidlyi that lungs from 83 Former short lifcspciri of kboratoiy animals could not deal tvde- cohort members .from the same company had been analy qtiitaiy: with rumeurswitha characteristic lateticyof sed by electron rnicmscfopy for another purpose some 5 30-40 yfs iti men,Thirdly, foe. fact-that ithasbeeri only .yrs e^tidr A'p^fiminaiy analysis, now published by ahaiy^iiigjlung tissuetifofUrev^iR&p |8S) has dctitdnsifated a remarkably close correlation be rous iremolUc has beeridemonstfotMin/^^ as ltween tlie high incidence of mesothelioma in a focalized produced commercially, and the growing probability that areooffivemiJiesaid the concentratirmoftremolitc tibia this previously unrecognized amphibote may bo respon in die lungs of men who bad workedia them 177]. These sible for mqst cfis or mesotlielioma associated with findings suggest that the relatively low rid, of ytesothuU- heavy ehrysotik;;exposnres.: ; oma associated with ciirysotilc mining and nulling may be When peace finally returns to asbestos epidemiology, largely determined by tremolite fibre comatmoation. Fur it nuy well be too late to restore ebrysotile's soiled repu ther analysis, which are now in progress, arc needed to tation. Like Caesar's wife, such materials most be beyond1 test ^'vKy^lin$et^aitd`a<s:Wl^pp.^fit^>; suspicion, and neither political nor ajdiuinlstfatiVe jxrli- tries are easily reversed. The more important Jcssotis from; : this saga probably relate to the screening and manufac Conclusion ture of asbestos sabstltutss - the man-rtiade mineral and organic fibres. Given what we now know, ii would sure After tieafly 40 yis of epidemiological reseafchi .t|fe ly he foolhardy, without extraordinary' justification, to al main dcfemaiuiuits of malignant. niiSOthalial tumours In tnan are reasonably clear. It could be said that this was: apparent from (lie start, when Wagner ef at 18] described low live widespread use of fibres which resemble crocldolite : and tremolite physically and the amphlbolcs generally in their biological persistence. a disease oblong latency in workers who mined, milled and used eiociiMitc, find in their family contacts, but rarely in miners of otliw types of asbestos. Sadly, die References picture soon became. confused tad ou r undcrsuindiiig. clouded bycontroversy. It is.worth cdnsidarii^ ihe rea 1, Wagner B. DaS iuberkeMti^tcfeLymphaderinni. Arefi sons for this. "." ...'. 2 .'. . ' . HtUk:1S70; M: 495-525, :' ; .. A major factor wiis thfit,;alihoi!gh it was cyident from ' % Sccccme A, Cobleiu A, RiitiM8ontttof dtcpicytsu Am cohort studies of chrysblik tranersaod- millers mthe ; J etia l'aiM im; 13: 138-207, - ': : 9: '3 T ?} :iq o 3 ;5 4 f ? 5 3 T n r 4 4. 3 4 4 :A,. ri mj*gftv,r-- C C. f 4:: "<V :-e .4*. <- c C, f. ,-c c: ft <*- at.. ft f. EP1DRMiflI.tR;Y OF' MPSOrtJEMOMA 1941 3. Gfajffiii SR, Two case# of squamous earcrrsmna of the .lung'Occurring Ittasbestosisi Tubercle t935', l?: 5-10, 4. Wedlcr JfW, Giber det! Ltntgcnktcbs bci Asbestosc. Dtsdt Arr.h Klin Med 1943; 191; I89-2W, Si Weiss A. Plcurakrcbs bci Lmsgcnasbcstose m vivo tuor- pMogiseh gcaichert MedizbiiKhc 1913; t; 93-9-S. 6. Lurcher P. i^tn^trPecfczeffeuniordes HaiKhicHs lKi As ., ' btstoss!, Ardt GetoV'.r&opailt Gcwerbeltyg 195-1; T3; 382-393. 7. Cartier P.- Abstract of discussion. Akk fadust liyg fad 1952; 5:2S2. 8. Wagner JC, SleggsCA, Marciaijit I', Diffuse plctnrpj riBftotfieliotiia aad 'asbestos raposutc in the North Western Cape Province. Br / Ind fad I960; 17; 2j*271. 9. tfamrflonti R, ScSifcoff U, CJiorg J. Neoplasia among: insulation workers irt.ihfc United Siates wtUf.speeiai ref, crcnee io inrnt'rabdoitttnal neaprasi^ AtwsfaAcad Scl 1965: 132:519-525, .. : R), Elmcs PC; McGattgbcy Watle.OL* Diffuse: mo-.1 theliotiw of dm pleura and asbestos, Brfad J 1965; 1: ; 350^353. . .. _ li, Newhousc ML. Tliompsen fl.: Hcsodrelioma of plewo and. periioncom following. cijujsure 'to -asbestos- in the London awn, Br J fndfad 1965; 22; 261-269, fii Mcfiwen J, Finlaysots A- Mair A, Gtfcsfen AAM. Mes6- tlieiiomalu Scotland. /Jr farf j 1970; 4: 575-5:78. . ;t3. McDonald .AD.. Harper A; 1st Attar: A, McDonald JC. Epidein rinlugy -of prirtrary malignant nrtsstrrhdial tumours in: Canada; -fencer 1970; 26; 9J-J-9I9. ' :l4l Rubino JF,,Sconsetii' 0, Domm A, Palcstro G,- Epideffti- btdgy^'of pleiirar, iiiiisethcliomi in nordi-wesien* Eutty .. lament), Br Jf ftid fad 1972; 29:r436-4A2,, 15. Ashcroft T. Epidemiological .awl jiusmtjtatiye: reJaiSoit- slujjw becween mesothelioma ;ond;aiitiaos oh Tyraejnde. J ain Pathol 1973; 26: 832-840. 16. Haiti E, Dakpieti P, Bohligll. Dabbcrt A.llm/. f. Retro- spccliw study of 150 cases of niemth^ibAkw Harabutj' w fat AkftAtbeiismed 1974; 33;4-37- ' " 17. Ztelhuis RL. yersiccgJPJ-, PSatUcydl llT. Pleural meso thelioma and exfjosuee to asbestos: a rnttospectiw: case- control study in Hie .Netherlands. IniArek 'Occiipfa.faon :. Hmltli t97S;36:T18; 18. tliCGi Report "and Kimn]iwdiibiiw fuT..tlnx. Wort^ng group ba asbestos and cancer. Ann W.Ae.cd So 1965*. 132:706-721. . 19. McDouaWJC. O^ecltlstfecMR, GibbsG^. iSrtcDonald AD. RosriierCE.T^ diryfibitie nune and mill workers ofQuebec. AreAErivi/w: Health 1974; 28:61-68. 20. .MoDonaitl 'IQ McDonald AD, Gibbs GW. Stemiafyckj JpEtossfeif CE;.M<srtaliiy.in the chrysotik*rwbcstoS'hiiiies;. and milts of Qnebcc. Arch Environ fleaUh 1971; 22: ,6?^6so.:. ................. ............. 21.' McDonald AD. MeDortald JC, bla!igj!ftnt mesotbelioina . in North Ajnerica, Cantx-r 1980; 46:1650-^1656. 22. MsGonaldJC, MotionaidAD,; Ejiklemloiogy ofrnesothc* ^ estiin^ctl innde&e.^' Prirvi-fad 19.77; O: r ; 426*4^6. . .. . , , 23. McDonald JC. I'fcMhhjiinplirat^^ .:posttrft to tsiMtei; Bftfttxm $jfaiiik-iSeni*ea 4985; 62: 319-32S. .. ; .. ;' m.: Ross DJ. Sallk DA, McDonald JC SWORD 94: sur veillance of wotk-rclated ami occupational respiratory disease in (he UK. Occvp Med J99J; 45: 175-178. 25, Pcto I, Hodgson JT, Matthews rR. Jones JR. Ccntirmtng tnetcasc in nnssotltcliotna- moriaHty in Hritain. Lancet 1995; 345: 535-539. ;... r ; . -Dari.'iV'I.Aft-riitliM.Snhihi-A.A; Fnvlronrtseirbilrnesorlti:- ifema mTuirkcy, 27. [ARC monographs on the evaluation,ofcarcinogenic risks lo Itumsns. Vt>j, 42i Silica and Stmtc Stlrentcs. Lyon, France, (ARC. 1987; pp, 275- 239, 28. Das PB, Flstchcr AO, Dervliiafc i'U, Ivlesotbcliotiu in an agrieulinral commonity t>f India; a ciinioopatholdgi- tl study, Aust NZ J Sdn; 1976; 46: 218-236 29,. Rutlhsclatd H, Mulycy SI. An inmniscd risk fqi bung- cancer-tnnficality associated wjtb sugar canc rartning. J Na<l CancerInit 1,982; 68:755*760. 30. McDonald JC Epidemiology of pleural cancer, fa*. Uirsch A, Goldberg M, Martin i*P, Masse R, cds, Pravenfion of Rtspiraiory Diseases. New York, Marcel Dcktat.impp: .65-73, 31, McDonald JC, luddcll FpK, Duframe A. MeDormU ADTlte 1891-1920 birth cohort of Quebec cttsyseille min- cis and millera; aidmfay 1976-1981 Br I fad Med 1993; 50: 1D73-.10S1, 32. Riolaito C, Negri E, La Vcccltia C. Kra E, Decarli A, Peso 1, An update ofcancer modatity among chrysotRt asbestos mineis In IMungcro, Nonitem Italy. t)r J fad Med 1990; 47: SlfMlU. 33, SIuis43*mcr GK, tiddell FDR, Logan WpD, Ecaadeniiout BN. The mortality ojfampbitoki miners In South Africa. 1946-1980, Br/tadMed 1992; 49: 566-575. %&, Armstrong BK, De Klerk NH. Musk AM. Hobbs MST. Mortality in miners amt millers of cnvitiolire. 1n Wcstom Andi. Jfo-JJtMf'(ifri98>l;45:5-|:3iiv. " 35: McDonald JC,; McDonald Al), Armstrong: B , Sebsesticn P, Colioft studyprmrjttaliQr mycnniewlitotnincfs ospossfl w trcmolUe. <3r- J fad Med 1986: 43; 436-44-',, 36. Ti^miEivKP;'BsnJtia^'ITt^SIwtxKi PC, Sweeftihiti PM- Further, follow'-up-.stody of workers from ait aj.bcsss,cctndfi: factory, BtJ fad Metl 1982; 39: 273-276. 37, Glik<i;i :G*G. Hogsitxit C: Lung canecr'amting asbestos/, cement workers: ^ Swedish cohort study and st review. Br J fad Med 1985; 42: 397-402, 38; Grmlncr Ml, Winter PD. PimictiQ; Powell CA; . Follow up stntly of workcra-manufec'urihg chryjotile asbestos/ cWiWtU prcdtisti. /rr y ind >./ , 1986; 43; 726-732. 39. Ifughes JM, Wcill^ij,' 40. Finkelstein M. Moitollty ajiiuttg wiptoyccsdrTiu tiHuariti asbfc;tos^ejJKnifaet(>ri%,Arfr'Rt:vA!"^ [984; 129:. 754C76ir' . fh. Alies-Patin AM, Vaiicron AJ: rMrttlr^,i(if.Vf^!p9-:io". a Ftcnch asbestos cetncot factory 194M:9fe 'Brifafai! < Med 1985: 42: 219-225, ................. 42. Magtumi C, Tctracini G; Bcttplcmu GP, el at. Mortality; 43, 44. .45 46. .47, Myoratori del ccmcnio-ttirtianto a casale Monfcrratc: urta studia di coorsc sturico. Med Imv 19S7; 6: 441--453, Rufl'n iCLyngsE, lud K, Koisgnart! 15, IftekJeoas nf can. ccr k) mortality among employees in dm asbcstos-ccmcnt . ieditstry fft Denmmk, Br J Ind.Med J989; 46: 90-96. AJbin M; Jaltobssoa Kj AdcwellR, Johansson M Wcllijdei .H , Mortality.mhfrsttwcr morbidity-in cohorts of aslxtstos- cettbzui workers and refetents, Br J fad Med 1990; 47: 632-61Q. ' ... .. .. ... ':, NcubefgCr M; Kwndi.M. tndividual asbestos exjursum: strutking and mortality - a-coliorl. study in the asbestns- cement todustry, Br J, fad Med 1990: 47:6(5-620, McDonald AD; Fry JS- Woolley AJ. MeDotuM JC. Dust exposure in an American cliG'SQUIe textile plant Br J fad Med 1983; 40: 361-367. Dement JM, Brown -DP, Oktm A. P-ollow-up stiidy of cltiysatilc tcxtile.workcrs: cotiortmonalitj'arid caw^wi* :trol analyses. Am J fad \ i9'S2 4. McDonaldA0.J:c^JS;W^ltcyAJ.McDonald JC. Dust . exposure and raarfafayfaLad ;Anscdati factory toirtg ' chrysolite. rnttosiic. nru! eroeidwliu: tit mainly textile man- ulaaure.. -Sr J tod AW 19$j; 40. 368-374. 49, (Vw J, Doll R. Herman C. Rums W, Ctaykm R, Geffc T, Relationship of mortality to measures- of environ- , mental asliestos pollutimi to sm asbestos textile factory . ,.. AwxCkcefl .Hy$ 1985; 29; 395-355, .. ......... . ' 50, McDonald AD, FryJS, Woolley AJ, McDonaldJC. Dust cxposumiutd.otOKalityiltv.aftArtvaican.cJsfysotyf': asbes tos Icktiarfproducts plant. Br/tndMed I94;41: 151-157. 51, NewlsOusdML,. Sullivan KL....^nalsy study ofworl> : ers manufactoring friction .matcm!*: 1941-1986... Bt J tod Med 1989. -16: 174419, 52, Seliftoff UiHantrttofid EC.Scidman 11 Mobility expc- notes .of insulation workers in (he United States asid. Canada. 1953-1974 A/m HYAcadSd 1979; 329:91-114: 53, Stillman H, Scliboff U, Hammond EC. ShortMenn asbestos week exposure and fang-icrm observation, Aon ftV Aced Sd 1979; 330: dt-SW 54, Achcson ED, Gardner MJ, Winter PD. Benner. C- Cancer in a factory using atmtsite .asbestos. In! J Epldenual. 1984'.13: 3-10, ;55, '.ricS^aldAD.^epo^W JC. Mesadtdfania after cov e^^itajsTO.tiitfing gas-mad: majiuYaaurt ' Jfawfaaitf' . fau.1978; iT:,54^34$.. 50: Ijffies-iSP,- Smith PG, Pootey' FD, a oi . ThaconaeqqerscxfcS of fcxpdsyfacTO asbestos'dtist-fa a 'wartime gas-. imskTikiory, fa;'Wfag#criG,fab Biojogicat'^ecus of Mineral-Bbrcs. 2, IA&G Scientificffabli'ostfaas'Nd; 34 ; Lyon. France IARC (980, pp. 637-653.' 57; Taloott IA, Thwbcr RN, li^utuor- AF, ..Asfessfas- aadtd diseases in! S colidfl.crf-bigwetiB-riiittr wotfc- cm. .Vrr^ 9AW 1989;;52i:: mi"im ' 58; Achesor. ED. Gardner ML 'PfapfafayBC, Gtinfa LP; .Mortality of,tw grixipa cf w'Ofitsn wlitj mar.ofaeturtrd ^imasksiftotts claysotile andcrbefaolitt asbestos: a 40 . yearfoliow-tip. Br J M AW 1982; 39; 344-348. 59. RiossitcrCE.ColiisRM.. HM Deekj-wtl.lTevwips'trt'M? faurtilJUt stsiiiy. in; Wander -IQ, etL BTdidgicai Effects of Mineral Fibres. 2. lARCSckittifie piit>licafi5S No. ;m t.ypn. T'ninee, IARC, 1980;# 713-721. . .. 60, Wcpaitsjld AD. Al&fact fa difatistion. /fa-tikir HW, cd. :PrCKetdi!tgs'Of xsbe5lo'S symposium, Johannesburg. South Africa, Oclolutt 1971* Nuiidnfa fasbiute-for Metal lorgy, Rantltiurg(1978; p. 82. . 61. LingerAM,.Nolan RP.. Ebrctype and burden in pare-itchy- real tissues of workcrs <>cco}iitiotw!iy exposed to asbestos fa Use United States, jo: Bigtion I. 'Fern J, Santcci R, eds. Nonoccupational Exjxisureto Mineral Fibres. IARC Sc'tectsfic PubUeations No. 90. Lyon, Franee.'lAftC. I9S9; pp. 339-335. " ,.... '' 162. ` McDonald 3C. MttJ^uialtj AD,' Mesdtbeliotrati is 'there ' a background? Eur Reiy/ir AVv )993; 3 (t t); 71 -73.. fintcrlino PlJ, Heiidasdn .Vii. .:i3c<t'gd^litc:.RatseotS far 'v pleural mcsottislioma deatlts in the Utttted Suutts. 196S , 1981c: J Uml CancerJtKf-1987: 79: 31-37, . 64, Fraire Afi, Cooper S, GreenbcrgSD, BaEflor.!*; Lingstori t'. Mcsodtctioiftaiti clwWhood,Cmteer l988t62:.E3fc647, 65; Peto J, Henderson BE, Pike WC. Trends in nwsotlie-- lioiua incidftricc and the forecast epidemie ducio asbestos exposure duriqg World WarIL fn: lhato R.'Schneitlerntan ;M, cth; QuandBctuion ofCccupctiorol Canccr, Banbuty Repon 9. ColdSpring Htubor NY. I981:;pp,,5lr72. 66;. Uw PvBnidHiBd:?, tQudod R. ef ai. Maligtistn^eur-' al ntesOdfcUorn#'associated with exposure tal&atia't|fc. Xmeetiim-, 344:: 17771; : 67. Boxtun C Vtallnt JR. Swinbauer J^DufaurG. GautBcfef A; Bitaterai f4eural plaques In Corsica; a marker of Ednoccupaiitma! asbestos exposure, fa: Btgnott J. Pcto J, Saracci R; eds. Nouoccupatwitat Exjiosun; to Mineral ; Fibres, JARG Selcntifie Publitations No. 99. Lyon, France, iARC, 19S9; 466-410. 68. McCotwothleJC,-Sinidnato. L, Mavrides-Preref. Mesxr- llifeltoma iit Cypras. 6t: Brgrujn J; PetirJ, Saraeci R. cds. Nonuccupsttonal: cxptiSbVe to mineral:! fibres,.I ARC SeieptilitlfabUcatiofts No, 90. Lyon, France, IARC, 19S9; - pp; 411-419, .....'. ... : 69. Gstdncr Ml, Saracci R,,> Effects no. health af nun-occu- paii(u:il exposure to ?.iri>3rtie HiitteraJ fibres, in; Eigtxm J, Pcto J, Santcci R, eds, Nomsccupalirmal Exposure to Mineral Fibres, IARC Scientific Publications No. 99. Lyon. France, (ARC, 1989; pp, 375-397, 70, ;l5ngcf Afi, lfap[cy FT). ItlentiBcydonofsinglc asbessos fibres in human tissues, fa: Itogovski P, Gilsoti.JC, Timbre11 V, Wagner JC. Biological Effects of Asbestos. IARC Scientific Publications No. 8. Lyots, France,- IARC, 1973; pp, U9-I25. ; 7V '.Jwltyroi': Ait ettmlmtiQO eT'ih'llMra'iiiitiMkMi' tent.of asbestos Itmg tissue from ihe CanadiArt ehtystuik mining industiy. fit won Res 1976; 12s 281-298, 72. Rowlands N. Gibl's GW, McDonald AD. Asbestos fibres . in the iungsof chrysoi.iie mine:s aiid iriiIicrs. Arid Occup //y^ i982;-26:411-415. " . ', ..... ' 73, Jbqes JSP,;RpbsrtS'Gfl,;Pooky PD, ei si, TTwethology ; v dsid'.mihccni:contettt of fangs in: easfS: of .mesotheliofiia . in the Uni ted :.Kin:gfJom i 1976. fa: Wagner JC,ed. Bio- lo^tcalEffeca of Mineral Hbrts,. Vol 1. lARCScientific ,TMiKifa!ias:No.-3i. LyotkFifaiee, IARC, -I9S0; jip. 187-- i99. : , ,.v. esxnkta offang itiiitsSottelidl tfatfaiirsin Nmtb AmeiAia. 4fatei;ttp:i^g J982;;26; 417^122;. 75. Mwr<r:.Gv :C5jdsetlf B. ffarty^tlFjjSfatug^ Hbte cou- ceotratiott fa tong lisstssof paftenk yrtfa malignant mdie Honiara easMshtrol study. .Cancer 1.985:56:1(^9-^1993. 76. Gaudidset:A, Jatison Xy Motkfatux G, tt-td, lAxsessnumt hy analytical miemscopy. of the iota! Ring fibre burdeiv in jiKSOihdtottta patietits faMehed;with .fiwr- otbsr- pathology . icalsctfas AonOccupliys 1988:32(Sxrppi.; I);213-223, 77. McDonald ^Armswciug.B,'GasrfR, dittl. hfesotheibama - and asbestos fibre-type, Cunicf 1989; 63:;-1544-154.7, 78. Rogers AJ; Leigh Aciad M.: RektfofaMp between lung-tisl^sioS'fiijreiyjst awl.coticetiifiuton fatil': relative d8; of ifas<>tbelifa'fi6:'3 case-control^study:. Catxer 1991; 67; 1912-1920.: ; 79; McOanald JC. TreriKilite, othcramplnbolcs, aud mesotbe- iiottuu Am J ind AWI988; 14: 247-249. ....... EO. Cfeurg A. Analysis of lung asivestos edment. Br J titd I *' tied 1991; 48; 649-652. - !'. 81. SdHwstkn P. MtDoni-ild JC, McDonald AD, Case B, Hadcy R. . Rcipiraiory cancer in cliryisotile toMifaland:. 1989; 46: 180-187. 182, ; Jbggli PC, Brody AR. Aslksros . fiber typd in irwligiiarit ntcsothdfamar.au analyticiil scaoning clcctrcut: ' fatitfaisebpjc sitidy of 94 cases, fyn J JfafiAW S993;:3!3:-: , ; 605t614- . .' ' .. . &L .^faDt^Idrifc-vEpRletmologicBVstgnific>itreof iitifafaat.. fi^; pasfatcniifc in liuman lung tissue, En'/nron fhSith: :Pir0etAmt^ l02(Suppl. 5): 2ll-22i 84, hfaDbnald AD; Giblw GW, Rowlands N, Cbtystfafaiadd irefablitc lurtg content of Qudfax mh*rs. Am Occup IJs HB2-1183.:V '' 85. MwohiitillE, McDonald AD. Chtysfaifa,;befaolik;iStrHl . moilieliom;i, Si'tVticc-1995;:267;.775-776- '