Document O1Y7K7VGqL7OZ3gVkDG5ONE5v
I
212.
Four cases of mesothelioma among Finnish anthophyllite miners
A Karjalaiiten, L O Meunnafi. H Pukkala
Abstract
theless; oftm constituted a large proportion
Foui* cases of mesothelioma 1 a cohort of the total fibre burden and could therefore
of 999 Finnish anthophyllite minus and: hot be excluded as;a;cause of inSsbfhelibma.
millers are described. Three deaths were In one of the patients with a reasonably low
due to pleural mesothelioma And one to concentration of fibres only anthophyllite was
peritoneal mesothelioma among the total detected.'!
:
r;;
of S03 male deaths up to 1991. AD four . Ih!.this report: We- describe: four:casCs of
patientswith mesotheliomahad hadlong ;mes6tijefiamarihat!c;C.p.urrsd. in the: ongoing
tertn <13 to 31 yeara) exposure In aatho* follow up of the cohort of Finnish anthophy!-
litc minersand millets.
time from the onset of employment until
diagnosis was 39 to 53 years. All four
patients were smokers orexwtmokersiind Materials and methods
:
had sstaetasis. lii three of the coses the TUB COHORT OF ANTHOPflYUTFE MJNBR3 ..
pulmonaryfibre.concentration:: and fibre Two anthophyllite asbestos quarries were
type were analysed by transmission elec*' worked in Finland during the'. period
iron microscopy.: High concentrations l9i$r75< They were owned byltfie same
(270 to 2100 million fibeea/g dry tissue) of :company and located.within .10; kni :of each,
anthophyllite: fibres were detected.. The othisr. in: a sparsely populated area about 50
aathopfaylUte fibres were thicker and: had km from the nearest city. The workers were
lower : aspect ratios than the values recruited mainly from the fanning population
reported for crocidolite fibres retained In living iu this area. In the: 1950s and 1960s the
the lungs ofpatients with mesotheHomJu annual output was about 10 000 tonnes. The
quarries were combined with a dry hammer
:: (Occap fowpS ;Atat:1994:iSI ;212-215) T;: -i:."
mill, which crushed, ground, and' classified
the broken rock into asbestos products for
various industrial applications:
Numerous: reports from RCvcrw! countries::' :' A fairly complete personnel register was
have described cases or series of pleural and kept by the company in the form of salary
pejitoneialmesdtheliomas to:relation to occu lists from 1936.: The register, contained die
pational exposure to various types and mix najnes, dates of birth, .working periods, and-
tures of asbestos. .In 1960 Wagner and roughly the kind of work dene. The series of
coworkcts described 33 oases of pleural< miners:. and riallet?;.; included all workers.
mesotheliomas: in the neighbourhood of a: employed for: three months or longerbewecn:
crocidolitc mine in South Africa.1 In later 1 January;: 1986 and 1 July, 1967 (miners,
studies, mesothelioinas have been found after millers,: forestry, workers, transportation.woffc^.
occupational exposure to crocidolite, amositO,: ets.: and: office .workers); After the exclusion
tremolitic material, and chrysolite asbeatos.2 r of workers who: could not be identified, the:
Eh Finland, anthophyllite asbestos has been follow up was completed in 999 workers up-,
exceptionally widely used: because of its; to the end of 1991, The deaths in the cohort
domestic production from 1918-75, andspe*: were researched through the death files of
rial attention has been focused on. the role of Statistics: pihland.:; The deaths , from $#ncer
Inlrtitttti; of
Occupational Health; Hlldnldjftiihiiul
A Kajalaloen
anthophyllite asbestos in the aetiology of mesothelioma. Anthophyllite fibres : have : . induced mesotheliomas in animal experi- * meats both after inhalation and intrapleural
were based on the tiles of the Finnish Ganccr
Registry.
.
HISTOLOGICAL VERIFICATION OF THE
'
Oepaortmearaf
<
Pathology, University
ofTurJcuiTurJoj, -
Finland - :
administration,2shut epidemiological studies
have lailed to firmly conneet exposure to anthophyllite and mesothelioma iahumans.
DIAGNOSES:
-,
.'.
In all four cases of mesothelioma: tissue sam*
pies takea from the tumour: at necropsy or
LO Mcvuman
In a cohort of about 1000 anthophyllite min thoracotomy were available for histopadiolog*:
Tlvmflth rjHHUW '
Registry, Helsinki, Finland EPukkals ' i
:
ers and miller, an increased risk of lung can*
cer was found.: but no confirmed cases of mesothelioma were reported up to 1977." In
ical examination. The diagnoses of mesothe lioma were confirmed. by the Finnish Mesothelioma Panel. Formalin-fired and
. ueilx -nponzin cp-v:::: o/iOccupaotMiiiI HeiJth, ' :.TipdLfcMktHu *J * ' SF-W?50;:Ii4lili^:Fmia2id;-
a more recent study of 29 Finnish patients \ritl> mesothelioma, raised concentrations of anthophyllite fibres often occurred in their lungs, but usually together with other types of
paraffin embedded tissue blocks were used in : light microscopical histopathologica!,.. and inmuOohistochemical examination.: In one of
die cases (case ;2 in table 1) a morphologically,
asbestos: fibres. Anthophyllite: fibres, never-. typical pleural mesothelioma with sarcoma-
I 1 l
2t3
aiuhct^lacmwny,) y.j..;. . y : !'...:' :.."' i!-:" ;."; MM>":' '
I ,;:.! .
; diagiikftii ':
?v':7Vwcwi:.::;|:!
21
:: sii:* : EpilteltU
. Pion**l : :: is8s.::...
Sueonuwui riwwl.-i- . :. -1987-:-- .
3 ay.
i.57 . . ! iSarwwwiiHSi;:' rpieoral:: s Epithelial
.y: 196b sai
-- No (tidpk
iifbviunw numnf-v
3I l9-$7 13,1929-56 29,1947-75 23,1950-75
r'iibb r; 270
.. {.IN . .. T '
i/tuauf
AfltbCffhy-ISt?:... ... , AatjlVpI^IUu; . .-
tous histology remained negative in cytofeer-
ariti staining and a sarcoma could not be
completelyexcluded- . .
-
.ANALYSES BY ELECTRON MICROSCOPY In three casts, a.. sample ..of lung' tissue was available for analysis of the retained mineral .fibres by electron microscopy. In one of these cates (me 2 to table 1) the tissue way stored in 4% formalin. hi die two other cases the specimens were embedded in paraffin, which was subsequently dissolved with xylene. As the tissue weight is known to decrease during the process of embedding due m the extrecdoit of lipids,* the fibre concentrations of the paraffin embedded samples were corrected assuming a dry weight loss o2G%,
A piece of tissue of about 100 mg wet ' weight was taken for the fibre analysis. The
samples were prepared according to a previousty described method,5 which included low . temperature ashing of the lung tissue: and fil-. . tratiotk ofthe remaitiing agli on polycarbonate filters. The filters were further, coated with carbon and placed on electron microscopy
grids. The fiber material **ks dissolved with Chloroform hi ;& modified Jafife: washer. The fibres were counted with a JEQL 1,00 CXA5ID4D electron microscope in STEM mode on a CRT screen: An. acceleration vqltage of 100 kV and a magnification of 15 OOO
TckU 2 bUnauioiu oJanthcpbyBiufibttrttnht limp of
ammsFimiskewhephymit WOMfj
1 W '4 :y ::i . J
Fftrttteiftil.turo):.. Riete Mein. Median Oiilrilnilioftvf: . ..
0-80-27 070-44 0-80-31 r 7-3 4-t 5-1
<1'Q 1-tM-O 50-** >10
4 [i2 f 4 50 55 44 26 14 2? 20 "29 .L.:
Fibre wvttl (urn): r
MRettm*e
U-05-T-1 ooo-t'5 O-OJ-l-S o-Si :: ,0;4<t.:v 045
. :::yO30 0'35 0*35
>.- DlfUibutiOflOf:
. ..' :ifibf*'wdljlk (W): ,
13 8 4
01-0-49
K (2 56
30 27 1s
>1-0 1 i to
AiKctntio (knzta^wKlth); ,,
Emit
3-0-100 3SHS0 3-i-n
;
21 14
25 Vt
19 i : 15 '
Of: - .
<1* J(M9 >100
::32- 34
33
5S m e
4
t .3
0
were used. All Inorganic particles having roughly: parallel sides and a length to width . ratio greater than three were defined as fibres andcounted. The dimensions; of: die fibres : were measured directly on. the.* screen with magnifications up to 100 000. The dimensionsoflOO.fibres.persamplewOrtmeasured. -
An energy dispersive x ray microanalyser (Tracer TN 5500) was used to identify the- mineral type of each -fibre. The intensity rados of Si, Mg, Fe, Ca, and Na were used-in the identification by comparing She: spectra peak redos to standard spectra. Four hundred ... fibres per:.sample were: identified, ..This gave an analytical seositiviiy of <0-25% for fibre types oilier than anthophylljte. According to Poisson statistics this equals: a. detection limit of <1-0% (four dmestheanalypcal senshivxtyfe: .
Results ' ' In-, a . recent..followsup of 999. anlhophyllice miners and millers, a total of 593 deaths (503 men and 90 women) were noted up to the end of' 199i;-72-of .these were 'were- due'to; lung cancer, four to mesothelioma, and 31 to asbe&tosis. The diagnosis of asbestosis was mentioned in 20%: of all death certificates. A detailed report on the incidence of cancer in this cohort is under preparation-
Table 1 presents the pathological charac teristics of the four mesotheliomas and the exposure data of die patients. Three of the workers had. pleural:.and one had . peritonea) mesothelioma (one of the pleural mesothe.Homes bed also invaded the abdominal cav ity). All four were male smokers or ex-sjnokels and had asbeatosis. The three casea with available lung tissue samples had a very high concentration of - anthophyflite: fibres in their lungs; about 1% of the fibres were coated asbestos bodies. When 400 fibres pr sample were identified, only aathophyjlite fibres were detected. Numerous talc particles were also detected in the samples. .
Alt fbur patients had had long term (13 to 31 yean) exposure In the mining of asbestos (see table 1). The occupational histories indiuued no. exposure to asbestos Other than in die Paakkila mine. As well as work in the PeakJdla mine, all fbur had worked in finning and forestry. They all retired when they left die company. The latency time from the onset of employment to the diagnosis was 39 to 58 years. They all had lived in the neigh bourhood of die mine before the onset of employment.
Table 2 summarises the measured sires of
T
!
"Sf.;' ' ' Kaiialaoun. Meurman.
the aflthdphyiljK fibres in the three cases, tile dimensions were similar. The median lengths: of anthophyllite- jfibie? were 3-9 to
29 Finnish patients with mesothelioma, the dimensions of fibres found in the iung tissue
Were measahed::andi-the same method; .a.s::iu
5-1 ftm with 20% to 29% of fibres exceeding our study-':hi:tbht srudy, the. crocidolite :|nd
10 inn in length. The median aspect ratios : amosite : fibres were- thinner (median width -
were around 20, and 4% m U % of die fibres 0*06 v 0-35fan) and had greater aspect ratios
had aspect ratios exceeding 30,
(median 30-0 tr 14-2} than anthophyllite
fibres. The size of the anthophyllite fibres
(median length 5-0
width' 0-35 ftm and
Discussion
aspect ratio 14-2) was in accordance with our
Four histologically confirmed mesotheliomas results (fable 2}. These median widths are
were found among 533 male deaths tip to smaller than the 0-61-0-73 /n in the earlier
1901 in a cohort of 999 anthophyllite miners report.^ on. RnrusK . anthophyllite! niineis,'1 -
and millers. There were no mesotheliomas probabty due mainly to. ffie: poorer;mplutW >
iamong the 90 female deaths: during the same- of Thin fibres at the lower, magnification::
period. In meu the proportion of death* from: (1500x) used in.thiit study,. .. .
mesothelioma (about 0-3% of ail male
As well as cohorts exposed in mining or
f-death*}?was:iess:disn::fhe;l'-5?5-tio 18-6% that: handling of asbestos, mesotheliomas have
have been repotted in cohorts exposed to o- .been - .reported:-.among ;taic; mipers,: whose '
cidofitCi amosite, tretr.olite, or mixtures con-; exposure could have included fibrous tremo- -
taining these amphiboles.' The proportional lire.71* Tfemolite has also been -detected in
mortality ratios obtained in different studies geolngicai investigations in the PaakWIa area,
might, however, not be comparable^-for bur the amount of fibrous cremolite has not
example, because pf different age structure of been documented.13 Exposure to fibrous the person-years in the follow up. For com^ : tremoHte-atadng the P^aic^ miners, is.there
padgon, the proportional mortality of fore geologically possible, hip teeraolife fibres
mesothelioma in tht.Pinnish: male population were, however, dittoed among the 40O iden
in 1982-91 according to the statistics of the tified: fibres per saddle in the Ifin* specimens -
, Finnish Cancer Registry was <M%. About hi: pur . study.- Neithir;.has. iremolite been ;
70% of deaths from mesothelioma in the reported: as a 'contaminant: in .the ..Inter
Finnish population are related to occupa-:-: national Union Bgainst Cancer (UICC)
nonal exposure to -asbestos; .mainly in ship-: anthophyllite standard derived from the.
building, construction; and maintenance Paakfcila mine,17 nor detected in products or
occupations.' - Additional: deaths ': from dust samples collected at die mine and mill,
mesothelioma in ottr cohort cannot be com- andanalysed in our laboratory. Exposure to.
pletdy ruled out, as only 30% of the death fibrous tremolite among the Faakkiia miners
certificates were based on necropsy, and pul is therefore, if not nil, prebabfy vety low. .
monary.: and abdominal malignancies were
The concentrations -of fibres found in the
included among the cases that were not lungs of the r anthophyllite miners were very
necropsied. The diagnostics of mesothelioma high. In Finland, with the same microscopy
have also: greatly improved in Finland during method, similar Concentrations. have been
the past: two decades. Therefore the accuracy repotted only among asbestos sprayers and
of death certificates in the anthophyllite shipyard workers .exposed mainly during
cohort: up to ifie 1970s may not be compare-: asbestos spraying (mostly crPCidoiitc}i3-::and: :: :
ble with the data of the general population in an increased risk of mesothelioma (OR 1-4-4,
the 1980s.........................................
.... . 90% confidence interval 2-5-178) has been
Despite these epidemiological problems,; it associated with fibre concentrations exeeed-
seems likely that although anthophyllite fibres - ing 1 million fibres/g.1* All our patients were:
can induce mesotheliomas in humans, they heavily exposed and had asbestosis, This
are less potent than crocidolite or - amosite might be related to the potency of saihcphyl-
fibres. This might be related to the differ litc fibres to induce mesothelioma) a reason
ences in the dimensional characteristics ably high level of exposure is needed for a
between anthophyllite, efoeidolite, end sufficient amount of fibres of adequate .
amosite fibres.
1 dimensions to be deposited ifi the lungs. .: -- -
: A model for the earcinogeoic potcncy of a fibre as: a function of its size: has been pre sented with the conclusion that long, thin
We tjcprw, our Tineefi. shanks to K*ii KaSwta MD'. Ttetc.'
'
^ 64MalArL^:;
i..
-0-0E4&lJiCLi)r->tui::tldnutj;ttEj^dDCUJ^;: XC3:;:tla
bttHLltttDOB.
fibres are more carcinogenic and fibrogentc
than short and thick fibres, but many short fibres may induce a tumour as easily as a lew-
Vy., .-V .. .
v'
long fibres.*-It has been suggested-that fibre*
8: in length and: s0:2 fttn in-width: (aspect-
ratio greater than 40) are the most important in the causation of mesotheliomas in humans,4 The fibrogenic potential of asbestos : fibres hat-iseen- conisid ered to correlate .with
-the total surface area of-retained >fibres?inde-
I Wfigncr. JC^
splniiaii::
mtwtbittoili;' :ifidv'iisfc$8i:Q
; Cipe^B=60ht71. f
& jtnterutiqiiiiiii;: Agtocy ftfe
fV iirtnot/imrunrH-
- :Wd* '
i9S7:i(HS^i:6;
- pendently of fibre type.16.Anthophyllite -fibres : are on the average much thicker than croci dolite or amosite fibres.11 fit a recent study of
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