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fintnh Journal o] Iniht.urnt! Mciham IVHJ:41.2S-3U
Incidence of cancer among vinyl chloride and polyvinyl chloride workers
SSTORETVh'DT Ul-LIMAS.' S L LANCARD.'' AND A ANDERSEN'
From liir Resenteh ( enter." Norsk ilnlto u i /`orsyrutoi Fuhrikkn. JWO /`orsyrinin, Jeleinork Senmls
fukthus,1 Depnrimetil o) ! ieeuptthotml Meilieint, 3VIIV I'oftgnutn, anil C tuner Reyisiry of Norway,' Mon
leMlo, Oslo J, Nornio .
.T
abstract The results of ii follow up study of the incidence of cancer and the mortality in a cohort of 454 male workers producing vinyl chloride and polyvinyl chloride arc presented. The study population was restricted to employees with more than one year's work experience in the study plant between 1950 and 1969 and the cohort was followed up from 1953 to the end of I97y. Twenty three new cases of cancer were observed compared with 20-2 expected; one case of liver angiosarcoma was found. Five cases of lunn cancer were found (2*K expected) and four cases of malignant melanoma of the skin were observed (0-K expected). The possibility of a causal rela tionship between exposure to vinyl chloride and>the d^vcloppiept of mtdjgnant melanomas is discussed.
Since 1974 when Creed) and Johnson presented
their report,1 human exposure to vinyl chloride
(VCM) has been associated with the occurrence of
angiosarcoma of the liver. Several studies have
confirmed these .initial results as reviewed by Spinas
and Kaminski.' In animal studies where VC'M was
given in mice. rats, and hamsters by different routes
of administration neoplasms have also Itecn induced
in other organs.1
p'"
' *
Whether VC'M lots the potency In induce cancer
in man in organs other than the liver has not yet
heen confirmed. Lung cancer.' ' brain tumours.' *
and cancer in the digestive system, primarily
angiosarcoma of the liver.*'* have been suggested to
he in excess in workers producing VCM and
polyvinyl chloride (PVC). and the prime pur|xisc or
the present investigation was to study the incidence
of cancer in workers exposed to VCM. with special
emphasis on cancers other than liver tumours.
Material and method
lion of VCM and PVC was started in iy50. VCM was produced from acetylene in the room where the polymerisation reactors were located. In 1967 the VCM production was partly uhered. and cracking rd cthylvnctiiehioridc (EUC) seas introduced as one of Iwtt production methods. The production of VCM was discontinued in 1971 after which time the plant was operated as a polymerisation unit Prom loss onwards VCM and PVC were produced in separate rooms; table I shows the volume of VCM and PVC production and the number of employees over time.
STUDY POI'UI.ATIMN
A list containing the names or employees who had started work before the end of 1974 and whose period of employment had exceeded one month was constructed Iron) the personnel register provided by the plant. The health department of the company has kept the health records of all present and previ ous workers employed from 1940 and onwards. These records also contain Mime information on the place of work of each employee. By combining these
PLAKT DESCRIPTION
The study plant is located in the county of Telemark in south east Norway. In addition to VCM and PVC the company produces fertilisers, magnesium, and chlorine in adjacent plant complexes. 'Hie produc-
Beteivetl Jo August WlO AcurpteJ 14 October IVKJ ,
Table I Anmuil vinyl ehlnriilr nml polyvinyl rhlnridr proilnetion uinl iminher of employee* in ilie \niily plum
UW4 proud VCM o<ml
IVSO-SS IWMWU)
lux 1-70 *1471
I4XKS- 'MSI 5*XM)
,MXXt-.XtXXXI None
VVC (uinll A'v of employers
11X10- 2MKI
2SOO- StxtO
SOOO-SlHMIU .StXKKJ-MXXKJ
t v so 4 V VO vo-no
1Jo-130
25
VC6026
2<> llchlwu. LungOul, will Atitienn
a wo sources ut inli>rm:iiinn a list of names wav con ufarturing plant before I97U may have contained structed which was presumed m he complete. The 51MI ppm VCM or even higher concentrations.11
individual records contained the following informa- The plant was closed for reconstruction a
lion un each worker: full name, dale of hirth, iden October 1974 and since 1975 the VCM in the work
tity number, Iasi knou-n address, dates (or ticginning ing atmosphere has been monitored cnntinuouil}
and terminating employment' departments in the with automatic measuring devices, including slant
plant ut which each person had worked, and the systems that warn the workers during even mints
duration of work, in each department. Data were leakages. Since 1975 the VC'M exposure level a
obtained for I2.V1 workers.
the production units has been below I ppm most eft;
r it was decided to restrict the analyses in male the lime. workers who had been employed (or ai least one 13 year and who had first been employed at the plant JOH n.AKS1):lf ATtONS
before 19711. These limitations reduecd the number Jobs considered to have been associated with hifl
3 ol subjects to 15-1.
' VCM exposure include production, autoclave clear ing. maintenance, and tapping. Owing to the great
KKTIMATION Ut- 1;.\I*US1IRI
amounts of surplus monomer in the PVC. one mi)
As si conseipicnce id the technical design of the also assume that the exposure level in the parkin;
plant and the process operation, the level of expos unit may have been high until 19711. Those working
ure In Vl'M in the past must have been high but no in the development laboratory which contained
industrial hygiene survey had been performed small autoclaves in small rooms, in the contta1
before IV7-1, listimates of the average atmospheric laboratory, and at processing in the customers' set-
concentration in llie past were based on sporadic vice lalHtraiory. may also have been hexvih
measurements that had been carried out with an exposed, but no inhumation about VCM levels u
explosion-meter" which w-as graded from tl9f to these working places is available. Nine different
KMI'5 ol the estimated tower explosion limit: \r.i. exposure categories were defined (table 2),
Ci|uivalent to -Kill ppm of VC'M. 'I wo sources of number of the workers having been employed u
supplementary information for estimating the VCM more than one exposure category. Membership of
eoneentration were used: interviews with workers, an exposure category was defined as that category ia
some of whom had been employed in the plant since which the longest lime had been spent. If an ind<
the start of production, and a suggested odour vidual had been a production worker for some yean,
threshold ol about 500 ppm VC'M. Based on this und subsci|uenily spent a greater number of years
inhumation, we have assumed that the VCM con a job ghat clearly entailed minimal exposure, hr
centration was about 2UIKI ppm from 195b to 1V5-4, would hy delinition belong to a low exposure cate;
alsout 1(11)0 ppm Irnm 1955 to I959, ahotu 50(1 ppm ory.
..
from 1900 to IVb7. and about lOltppm from IVhX
As the exposure level was high in the early 1950s
to IV7-1. During autoclave cleaning the ex|tosure an attempt was also made to classify the jobs a
level may have Iseen as high as 3l)lH) ppm.`" Both determined hy the exposure level, using the numbei
emnlsiiin I'VCand sus|>ensiiin PVC'were produced. of "years of Stitt ppm" exposure. The procedure wn
The surplus monomer m the I'VC leaving the man- us follows: one year of production work in 1951
Table 2 ()h\rn nl lOl mill rx/irrird Ih) tlrwlii from nil ruusri, and nil nrtr nun n/rnnertin Ihr study population rxetpt liiin-melninnitn skin i umvr
iu/Htmrr
Mi ttf **xkrn
1)1 Vinyl chktfHk' (iuVlkkTK.-) It; Vmvl t-hliinUi-(l-IX'l
Kt'M'am'h kiNtr;iiir\ IW Kilyvtnvl chkKMiC fHniuctuHi M Auitn'invc I'k'nmny
0? iWktopUrytnp OS t uuunu-rs u-rvm- liiNiruiivv IN
'total
'Nf * Nut calcuLiwJ
17 K 4* in n o
vs
M) Ml
4*4
Ait itrGlhj
U /.
1 2-41 II li-MI
j-x: IV Ink:
s .VIU
4 7-AJ 5 *44 7 X-77 7 7.Ml
Ml 59 54
Oil.
Nf Nt` IM* tin
os: ll*V O-Xd (VK
(kKj
All rnntrn
a t:
n ll-KI
\ U-^ll
n l**V
V Mil
2 1-10 i 2X7 5 2-US A V(I6
2-44
t'S 20 in
nn:
Nf
Nf Nf l-7ft I-V4
Nf
t-M IkVK ox:
t-14
FctioH'Vnfi /VJJ-7V
56X.X IIOU 912-0 :3nx-5 31N-S KHH-V 1142-5 loess V71-J
K676U
VC6027
I
mi Atuimen
incidence of cinicrr wnony cinvl chloride and piolyeinyl chloride workers
27
contained uon.s." ruction in the workcontinuously
rtudinp.; alarm even minor ft level in
I ppm most of
II
[I I I I
when the working atmosphetc contained about 2000 ppm VCM on average, was classified as four *.500 ppm-years " The same type ol work in 19bI, when the atmosphere was alvnui 5(1(1 ppm. would give one 500 ppm-ycar. Tins additional eaiegorisa-
lion of exposure could he given for VC'M piodut* lion. PVC produeiion. autoclave cleaning, inaintcnance work, and t'VC packing. Owing to Hit- surplus monomer in the resin, one year of packing I'VC would give ahoul one 5(1(1 ppm-year lor eaelt year
poses and the expected number ol deaths are based on the national rates..
Remits
Deaths Irom all causes and the number of new cases of cancer. excluding non-ntelanoma skin cancel, are presented in table 2. The number of person-years at risk is also shown together with a tabulation of the nine different exposure categories. Among men
up in 1970. and it is even possible that this high level there w-cre 5(1 deaths irom all causes (expected
- continued until 197-1. in this wav high exposure for 59-5).
ted with high
short periods in workers ealegonwi! by jobs with" During the 27 years of follow up. 25 new cases of
woeUve clean-
low exposure level could tv aeeouiileil for,
citnccr were found against 20-2 expected. The nine
j to the great
All workers weie plaecd in an exposure category * exposure categories have been combined into three
fVC, one may
before we had any know ledge ol their stale of health groups reflecting high, medium, and low exposure
'at the packing
or diagnoses.
(table 5); the increased incidence of cancer is
Those working
accounted for almost entirely by the high exposure
iLich contained , FOLLOW OP
group.
in the control
Tltt main clement ol the method is in identify those T here was only one liver angiosarcoma, recruited
customers' ser-
individuals who meet the criteria lor memtvfsliip of from exposure category (M. und litis case has been
been heavily
the Study population and to eompaie this population included in a previous survey.1
' VCM levels in
with a constructed Norwegian |>npiiluliim whose age Table 5 presents the observed and expected
Nine different
distribution was identical with that of the study figures (or some malignant neoplasms of interest,
d (table 2), s
group. (The method lias been described in more l-'ive eases of lung cancer were observed in the whole
teen employed in
detail by Langhrd ei / |
study population compared with 2*K expected. The
, Membership of
Tola! mortality and caned incidence trout 1955 to 'mean time Iviwven first exposure anti the time of
it that category in
Iht end of 1979 have Ivcen determined lor the study diagnosis (latent period) in these live eases was 17 2
t spent. If an inch'
pipulation. The Cancer Registry in Norway has years (range 5-2h) (not shown in the table). Four of
ipeitet lot some years,
records of all new- eases of cancer since 1955 and has the live eases were in the high exposure group (I-K2
vcamber of years at
access to information tin all causes of death provided expected).
jwiima! exposure, he
hy the Central flureau ol Statistics, `flits study is
Four malignant melanomas of the skin were
11 bw exposure caleg-
based on a comparison or observed and expected identified in the study population whereas only O R
i total mortality and incidence ol cancer lor the was expected: three of the cases were observed in (kin the early I95CK, 7 period I9A.V79. To estimate .the expected number the high exposure group (t)-5 expected). The
ciissify the jobs as of eases of cancer, the national five year age specific tumours were hvetited as follows: two on the trunk,
1, using the number 7 incidence rates were used. According to the data of one in the lace-neck area, and one on a foot. After
..The procedure was | . the Cancer Registry, the rates of cancer incidence in the observation period one more ease has been
n work in 1951. i ' the Telemark county are between 0-9(1 and 0-V5 of diagnosed in the medium exposure group; this was
the national figures." (Tinwipicutly. the more rob in the faee-neek area. We arc aware of one case of
ust national rates could l>c use'll lor reference pur incipient malignant melanoma located on the trunk
mij population eirrpi I
/V.U-7V
Table 3 Brood enlegorin of work indicium;: espns'iire h-i'W. tlhsen'etl ID hind c.v/MV/ri/ tljdriillts from nil mutes, ruses
1 ojntncer (all sites I, eolon euneer l/( II
Iirmnimd riinrer I/CL) /f>2//ei.ll, nuiliyimnl tnehnttmut oj theskin I/CD !W).
' and cancer of ilie thyroid ylnnd Ill'll /VVl. lot mirk Inhel, see lulile '
l.ipmutr trvid'
hinnij mukm
.-I It i inn er\
It'D / 5.1
It'D Ih/lln.t HD toil
l(D IW
rman- vrarz
o i,
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in. n r iid. ii /: nd. o i. ltd: a i. on:
tump i tiinup;
CmpJ
2vn ten Ml
is t-j 3 tin; -.t j i s; ; ; 3 i 4 7S us n n.vi nc ti im>7 nc t 3 :-4J is* 11 imk NC I 0-35 NC II
mi 5*1 ; imk nc u Will NC II
mi iho 5737-u imu nc tin s U-li: NC 971-5
I'] Ini!
454
' Join I t 3 1-44 ' I 5 3-K4 l-K 4
li-Tv 51 3 ISIS 135 KOMI
I '(lump I (kith vin)I i-MiiihS' vv|-ir, ( Wink InlxK ill. 113. IW, U5. (In. (17. ; f-inup 2 (medium vinyl rtilufik' f--ur,-) -- 11ml l.ilxl, u.t. UK, ,t (itiMp 2 (Si* vinyl vhiiuiUe i-(fvtMifL') - Wink Llvt in.
NC Nix calculat'd.
:
N
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*vt**vr taw it) Urst
MV) tillttf**l*\l`*l
i*ni*Jn\tiH`ni
h \ f*/n: t.i (OhJ r2 iHn i.i l`ir>: 45 |orK S| )Mlf M |MMI
nl 4> \*m
54 M 5* 5ii (*/o* 70 |`MI :* |W|,| JS
l* l*i'3 (*M \
40 \'tS* 41 |OI*| a* 100 1 14) i*ihj
1)2 )m; y\ |*/57 <<
)'r*ir */ ZivjrnoM.i
iiii i`iiii l/72 1 Ml 1 fill loll l*lhl IV7K |i77 1071 1 v7 J 1073 101,7 1070 |oM 1 *tn 1 iwm 1074 1071 1070 to?: 10l.lt low,
it v Sit*
i*i i*i I*,* i*\ !'7
no NO 171 n>: i oj ii.: Kt2 m I7K INI t'Ht MMl toil (V0 too ivo lol tV4 1W
hipntvrt ivrrjronrH
1)1 O' o.t 04 Di Ot 07 m 2 5
5 it
6
2 II
5
i II
t 10 IU 2
j 15 IK
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4
4 14
13 15
:
*1(7) I 5l (suwoieh earuvr). HI) 155 unlun ranmt. U'U 155 (cancer ( the hiiiars |ww#ciand liver), ICO 162/165 (Ion# and cancer). H I) 177 (cancer o( Hie ptisiaiel. H`|) 17H (tcwi* cancer). ICO IN) (hiadder ranee/). ICU IVU (mahjnani mcUno
H I) IV4 (earner of tin* Ihumd eland) l ijfc^urv cairpttnct cnrrc^indmp Kill) ilic numlvrv in table 2.
I Hio e^M* Hectored alter (he end of id^crvaimn period.
ca*c.
VC6029
.Ill
pinions have (veil siwK'iiili'J will) the devcloptncnl itl IIk'v tumnuts. 'I i';ii (..i'. (o-clilurtiaivloplii'niuie1 jiml |Milychloim:ili'il biphenyls'* me cheiuicnb Him "time Iven suppcsicil its possible inducers. In tun . utility |*i|iiil.'iinni mu- linin' caw ul iticlminuiii hits
tieeri di.'ipnnscd idler I lie clnxuie itl the study mill lielmc tin- iiK-ii'.-iseil incidence of tumour win known In m. 'Iiiis ndibtuwtul i'.'iv considerably xiienpihens
tin.- association iviivcen exj*o*iuc in VCM mnl the dwclopuieni ul mulipmmi iiii'lmioiiinv. A' the medi cal services in llie 'I I'lcmnrk county haw l*cen ol a hijjh ipinlilv anil easily accessible. e tin no) believe Dial I lieu- has heel) liny linn, tine In llie presence of Die tteen|iaiional health service in Ihe company. In laei. none ol Die loin niyi wav diapnosed by Die oeeupaiional physicians. Due of Die five subjects will) skin cancer half survived until June I'DO. The ineiileuee ol inahpmini tnelanoiuas in Die rural ureas ol "I cleiuark comm is shchily hi|iher Ilian the ualinnal rate ivliile Die incidence in uihan ureas is toil Is eipial in Die national rale." All subjects with skin caneci hail liied in Die urban area.
We iibseivcil ivvn cancers ol Die thyroid plnml (II-In expcctcdl: both cases K'cnricil in Die hiph cx|iosiiic pump amt xxcie ol the same hisinlopicul lyiw. We aie not awaic ol other studies indieatinp an excess ol iliiv i\|m.* of cancer lull as nub iwn cases liaw Ik'cii observed, tin conclusions can he drawn.
In a Canadian study on workers exjmsed In VCM lot Inc scars 01 more I licriauli and Allard showed
an excess ol cancer in Die ilipi'xtive system.* hut Die
tiulhors fonclutled Dial Hie excess is aecoumed lor exclusively hy cancer of Die fiver, in llie.prcseiil simly nc found a shphi excess of cancer ol Ihe colon. Many ul Die oilier studies relened in include cancer ol Die liver in dipesiivc cancers, and Drey conclude Dial Die excess risk is due to (Ills luinnur. 'Ihere me lew tepoiis on ncenpaiionally imluced cancer of the colon ami rectum nlilumph il has liccn imlicaicd Dial asbestos makers, icxlile svorkers, and Med workers
liavc an increased risk from these diseases." Watrials.' ct ol in (licit kinetic sillily showed some laccal cluuinaiion ol `'Caller Die inhalation of "C-VCM. Inn they discuss only urinary and pulmonary elimi nation in ilieir paper.'*
The icsnlts picsi'nicil in Die picseni sludy. ciinsiilcicd with oilici cpidciniolopical siuilics. seem In supiuiri Ihe view Dial \VM nun act as a muliicarcniopeu in man. This is in accoidancc witlt observa
tions Irom animal studies.' Some ol our Undines diller Irom those piescnict! by oilier workcis, and will lw followed up later. 'I lie observation fieriod is short lor sonic of ihe rucmbcis ol Ihe cohort, ami the simly pump is small. Nevertheless. Die lael Dial Ihe excess of dillciciti cancers was seen in Die pi imp mill ibf lu('bi-.i I'siiiuaii'il i'\|sisure level sireup-
llrhlmn. iMiifihril, ami Ahilenrn
(hens Die wippested uswwiaiirm between VCM exposiiu ami these tyfies ol cancers. in particular Die nudipnnnt melanomas. We thank Die Clastic Division of Norsk I lyilro ti s hit too|viitiion Duouphitut Die study. () C* liocktnnii'i critical eonuneiiis were of prent help. We thank Mn P A I tot lot imcnisiic help and Mrs U Dstnielxcn Ini lypiup Die nianusenpl.
Kefrrenres
> t ii-isii It .
MN Anfn-iuiMiu* h*rt in Hit manulaf
tutr ul fsilviMnl diknik, tf IM 1X174: I*-I MM. *' kjttii#. K. kMiHtsli K, Anivwittimii nt tin birr m vwii'
iliiHhli'
rtiSok surkrri. IV77 update ol IS
,, NIOSII irtisii-t! /OAf IU7x.*tr J77-V,
`hlabnm f. trli-minr f'i. Cilihrm A. I nni C. C'arreiii D Cm
<in*iprimitv Iwmwp id viml rtikvndr mminmer: mndrl a risk iwurM on an ts|s-nmenial havs. tjniron IIrata
/'myaii 0cl.4l:\JV. * Xi. **** HR. IVii'f. IX). Jtdmuui MN fmp.vn.wial morubf
Miimi vinyt-*4iXvidr waliti. Ijmirt IX74:ii;1V7-S * IMirivlias (il. tiatlry WR XXonabty sludy l wktri in Ik
" mavivilaeiuic ul vinyl cttSadt- and us ptfitica It)* 0174.1* uni IK
* VVai.t-ilri RJ. huiliyi-r XV. Xl'apvu'i JK.innci J. Falk II. fan.
f- Ni'.vjvOvik vi ansvny vnukcrv rarnwrd m sitvyl rhbvc Atm ,VV Ami .So l1/7h;J7l'4n.K
' llullV.'i I'A. Wins) S. liilk-i C. Suaicr L. Rikan I)J Mom'
rvs'is'iHv <a v.,Miffs in a vmvl ekilnridr mivfxvfncf fM.vJuo.
plmi.JitU pi7V:ll:l'is Jit;.
* li AJ. l nllii'i IT. Miaialnv i-iifvni-niT *4 siuken etfsirr
uml tiiXiihk flHHaHiH-i in llif manuluiluit ul fsdysi
OibHak' Mi I m'al Hot am Hr i Iml Mnl IV77.J4I-IU,
* IIh'ikhiIi (i. Altai il I', laisvr nutrialiiy nl * mup ut Ckni* sniki-o i*l|sived lu vinyl elilnodi' hsmskivci j
Owi.l.lMl *.
" lUMif- AXX VinO rtilvvidr aisl (Ik- pnstnrlHin lit PVC*. 1`iar
inf* hi dn1 Hniiit .X*irn nf Mnluinr l't7*'.AV.J77-j<|
" Kaidwli M I'V't ' hrillh implHUiHiAv and pruductiim ui t niiiiw llnilih I'tnimi Ol7h;l7:|il7-I.X,
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