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Journal of Occupational Medicine A August 1974 Vol. 16 No 8 Mortality Study of Workers in the Manufacture of Vinyl Chloride and its Polymers* Irving R. Tabers haw, M.D. and William R. Gaffey, Ph.D. Animal studies have shown that inhalation of vinyl chloride produces in rats angiosarcoma of the liver as well as cancers of the lung, kidney, skin and other sites. Although workers in occupations involving exposure to vinyl chloride have been found to have an increased risk of hemangiosarcoma, no excess of other cancers has so far been reported. This historical prospective mortality study of 8384 men who had at least one vear of occupational ex posure to vmvl chloride before December 31. 1972. demonstrated that cancers of the digestive svstem (pnmarily angiosarcoma), respiratory system, brain, and cancers of unknown site, as well as lym phomas. occurred more often than expected in those members of the study population with the greatest estimated exposure. The mortality from other cancers was lower than that of the general male population, with the exception of cancers of the buccal cavity and pharynx. There was an excess of these cancers, which however was inversely related to estimated exposure. The explanation for the latter finding is not apparent. The other major findings of the study are: (1) The overall mortality of the study population was ap proximately 75% of what would be expected in a comparable population of U.S. males; (2) No cause of death showed a statistically significant excess over what would be expected in a comparable U.S. male population; and. (3) No deaths identified as angiosarcoma of the liver were, found other than those previously identified. This is the fir<t epidemiological study which suggests that in humans vinyl chloride may also be associated with cancer of multiple sites. 'V* ' jn<1 S i- ml) JiittSJ ai>* mim r.jnt*f*na* *41m .f*r 'jrc h whuh wv.t\ K***i* .I'M if iHiKmiTi/jtion .if yinvl < hlon*l* anti ^-vk ation ,, .it,.* Mnit- *iH. F^jnv*- rthij :n a i**ni*a^t*<| -n 'ht- .n :N-ir hv *h#* Man**Ms Journal of Occupational MedicineJVol. 16, No. 8/August 1974 50g VAB.0001192122 4 V invl chloride m Us manufacture and particularly those producing the to have had the greatest exposure, while monomer, this determination could be those with low scores will have had the polymerization has been identified as a made on the basis of job titles. Usually, least, even though the true exposure m narcotizing agent,1 as a liver toxin,2 3 however, exposure was a function of each group may vary considerably from and as a vasospastic agent producing a both |ob title and the location of the job person to person. r\ r J * l} * 1 1 specific occupational disease, in the plant, so that the assessment of ex The estimated exposure history of ^arh acroosteolysis.4 Recently, vinyl chloride posure had to be made on a case-by worker was summarized by calculating bo* has been incriminated as a carcinogen case basis by plant officials. an Exposure Index (El): This was done be producing in a group of workers Data were collected for as far back in by multiplying the number of months on tor engaged in the manufacture of polyvinyl time as complete records were kept. In each job by the exposure score, totalling chloride a rare fatal liver tumor. hemangiosarcoma.5 Large doses of the most cases this covered the entire history these overall exposed jobs, and dividing of the plant. In others, records were kept by the total number of months of ex Ca chemical in rats reportedly produced cancer of the skin, lung and other for a fixed period such as a decade. In a posure. few. records were kept for different Sea organs.6 Unpublished but public in formation7 indicates that inhalation ex periments with rats in doses easily reached in manufacturing operations produces in addition to angiosarcoma of periods, depending on whether the worker had died on the job or had left employment. In most plants it was impossible to quantify exposure. However, industrial Follow-up of Study Population A follow-up procedure was instituted for those who had left employment and whose vital status could not be deter mined at the local plant, using direct f ob to in the liver, skin, kidney and other hygifene and safety personnel in each mail follow-up and retail credit bureau malignant lesions. The present study, however, was n9t restricted to the conditions and ' fries suggested by the above investigations, but concerned itself with the entire spec trum of causes of death, to the extent permitted by the size of the study group. The objectives of the study were: (1) To plant were able to identify certain jobs -tfnd locations as involving the highest exposures in the plant, and to classify other exposures as medium or low relative to the "high" represented by the jobs with the greatest exposure. Con sequently, each exposed job in a worker's history was scored 1, 2, or 3 to investigations. Table 1 shows the vital status of the population as of December 31. 1972. Follow-up is 85% complete. Those who were not found were born (and began their exposure) about ten years before the group on which follow up was complete, and had about half the duration of employment in exposed t I % I 1M dv ca: ca! the wt sat compare the mortality of individuals who have worked in vinyl chloride plants with that of the general population; (2) To compare mortality patterns within the population of vinyl chloride workers, based upon estimated occupational exposure; and (3) To com pare mortality among vinyl chloride indicate low, medium or high estimated exposure. This gross classification has two major failings, as a result of the subjective nature of the estimates. The first is that the scores represent estimated relative exposure within a given plant. It is therefore possible that, in objective jobs with a slightly higher El. Although there appears to be nothing very unusual about this group in terms of work history and exposure, it is nevertheless true that their exposures took place further back in time than that of the group suc cessfully traced. It is therefore possible that their mortality, after ysubstantial I i w< *ra ea th< sir w: th* workers with the mortality of other oc cupational groups. The study population consisted of in dividuals from 33 plants who had worked for at least one year in a job in volving exposure to vinyl chloride before terms, a "high" score in one plant corresponds to a "medium" or even "low" score in another. The second is that the scores usually do not take into account changes in exposure over time. A worker with long service may latent period, might show a somewhat different pattern from that of the traced group. All of the subsequent analysis is con cerned with the 7128 workers on whom follow-up was complete. Table 2 shows * w * * i P' ch w S.s se December 31, 1972, and included retired and terminated as well as active workers. For each such worker the date of birth and an employment history were obtained, and the vital status of the therefore have had jobs in the remote past which involved "low" exposure relative to other jobs at that time, but which might be "high" in comparison with current exposures in the same |ob. their distribution by duration of exposed employment and the year in which that employment began. Although almost half the study group first entered ex posed employment in 1960 or later, I 4 w 1 dr K worker as of December 31, 1972. was ascertained. For those found to have died, those death certificates that were available were obtained and the cause of death determined. The observed mor tality was compared with that of the This subjective classification is therefore of questionable validity in characterizing the exposure of a given worker. For epidemiological purposes, however, those who have high scores can reasonably be expected, on the average. there are nevertheless 854 workers with 20 years or more exposure, and 1640 with 15 years or more. Table 3 shows the relationship between duration of ex posure and El. There does not appear to be a close relationship between the El i I I4 4 vv United States male population. Data Collection In each plant, data were collected for each worker stated bv the plant management to have been emploved for at least one year in a |ob involving ex posure to vinyl chloride. In some plants. 510 *VCMt Tablt 1. -- Followup Status of I3M Vinyl Cftloridi Wbrkors, Total I3S4 100.0 ASvo 6774 SOI Du* 3S2 42 Unknown :s4 150 Owth Cnrtifleatts iKt M IkT. 121 24 92.7 73 Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabarshaw, Gaffey l VAB.00011921123 f 1 and thr* duration or exposure, 'hat i* .vorkers with a higher El do nut <tutor substantially in duration of exposure 'rom those with a lower FI One im plication is that in assessing the relation* a ship between mortality and exposure, both duration and level of exposure can be examined separately, as well as in combination. Calculation of Risk of Death The risk of death is expressed as a Standardized Mortality Ratio (SMR). which rs the ratio of the number of observed deaths in the study population to the number of deaths to be expected m a comparable population or U S. males. SMR's were calculated for overall mortality and for 33 major cause groups. Table 4 shows observed and expected deaths, and the SMR. tor each of these causes for the total study group. In calculating the SMR's tor specific causes, the 24 deaths for which no certificates were found were assumed to have the same cause distribution as those for which certificates were available. In the standard population, each SMR would be equal to 100. Therefore, the statistical significance of the deviation of each SMR in the studv population from the expected value of 100 was tested.9 A single dagger indicates (hose SMR's which differed significantly from 100 at the 5% level, that is. which had a probability of 05 or less of occurring by chance. A double dagger indicates those which were significant at the 1% level. SMR's based on fewer than five ob served cases were not tested for significance. Table 5 shows the same SMR's for workers with an Exposure Index below 1 5 versus those at 15 or above. The dividing point of 15 represents a level nalfvvav between 'low" and 'medium." Table h snows similar results for workers with less than five vears ex Table 2. -- Distribution of Months m Exposed Employment by Tear m rthich Exposure Befan, for 7121 Vinyl Chloride Workers with Completed follow-up. fear ip. Starlet L930-39 L940-49 1950 59 1960-69 1970 71 a ii Total <(0 25 1048 1962 2268 715 2 135 289 1714 715 60-119 4 93 257 1442 120-171 1 119 383 195 Vonttu of Eiposure 1*0-239 240 299 200-359 4 6 1J 151 277 237 631 282 360419 5 34 Unknown 2 20 17 Total 712ft 2155 im 91 7*6 565 250 39 l 39 posure versus those with live vears or more. In order to examine the possible in teraction between duration and level of exposure, the study population was divided into four groups on the basis of both El (low vs high) and duration of ex posure (short vs long) using the same dichotomization as Tables 5 and 6. Table 7 shows the results for short ver sus long exposure in the low El group, and Table 8 shows the same comparison m the high El group. In each of the above tables, deaths for which certificates had not been received were assumed to be distributed as a uniform percentage of all causes. The cause specific SMR's were therefore ad justed upward bv a percentage which varied in each subgroup. Results of Analysis The overall mortality of the studv population is statistically significantly lower than that of the U.S. male population. There were 352 observed deaths compared with 467 expected, for an SMR of 75. Table 4 shows that no specific cause of death was statistically significantly greater than expected Several, par ticularly heart disease, accidents and 'other diseases" not detailed m the tables, were significantly below their ex pected values. When the studv population is divided according to intensity and duration >>i exposure (Tables 5 and 6) and com binations of these measurements (Tables 7 and 8) three maior patterns emerge For malignant neoplasms as a whole, the SMR increases with increasing ex posure. whether measured bv level, duration, or both. In the high exposure group with 5 vears or more exposure (Table 8) there are 36 observed cases and 26.11 expected. For cardiovascular -- renal diseases as a group, there are also increases in the SMR with increasing exposure, but the numbers of observed cases remain less than expected, the differences being statistically significant in all groups ex cept the high exposure, long duration group in Table 8. For all other causes, there are no con sistent relationships with exposure. Within the malignant neoplasms, the largest (although not statistically) significant SMR is in cancers of the buc cal cavity and pharynx, with five ob served. 2.84 expected, and an SMR of 189. However, Tables 5 to 8 show that all these cases have Exposure Indexes below 1.5 and four out of the five have less than five vears exposure. Table 10 is a listing of rhe<e deaths with age at death, duration of exposure, and cause as stati.*d on the death certificate. Cancer ot the digestive 'V'-tem -hows Tibia 3. -- No. and 1 of 7121 Vinyl Chiorida Worktrs by Months of Eiposod Employment and Eioosura indat Journal of Occupational Medicine/Vol. 16, No. 8/August 1974 511 VAB.0001192124 f Table 4. -- Observed Deaths Eipected Deaths and Standardized Mortality Ratios in Vinyl Chloride Workers. Cause ot Death with LC D. Number 4N jus r-wz^'zi*i 00: 0191 r .p*c'y)osis tA 'so*ritorv wi?m <00! Mahgnint neoplasms (140-205) Manpint neoplasms, buccal cavity and pharytu (U0 1481 Malignant neoplasms, digestive organs and peritoneum ISO 159) Mal'tnint aeoolasms. respiotory system (1*0 1*4) Mshjrtiflt leooUsms, lemtil ^gans (170 179) neoplasms, jrmary :rgats i !30 131) swjpijsms, Dthef jnd 'jnspectfted >.t*s 190 199) V-;u^rn3 and ileukemii (204) -emc*:?n3s J200-203. 2051 Obstip 352 4(7 21 15 7! 1 5 i4 79.77 '6 5^2 34 19 2! *7 :s 23 93 3 3 55 l 3 50 :i \\ 75 3.3 77 $5 06 2-scefes ^e'litus *260) - ?6 31 Vvpr ;jfd:jviscuiar jnd ^enal j>sesses ^ 320 334 400 4*58 592 5941 Vis:u?sr esions jffecsng CNS (330-334) 3rev-'jric >ver * cnrpmc -leumatic heart lis. t4G0 402. 410 416^ -fT-r ^sclerotic `itaM d;seise `420) Xcnneumatic fndocardttis (42). 422) Hypertensive heart disease (440-443) -f^er ^oerensive disease 4*4 447) Ck.^n*c 4 unspecified "eobHis * renit sclerosis 592 534) 155 207 46 13 24 48 5 6 3? 121/12? 33 1:658 3.9 33 3 2 60 0 4 27 TM*en:3 3io ;ne*jmcmi .480*493) 59 96 Ulcer a* stomach and duodenum (540. 541) 2/3.83 Aopendicms *550 553) 0/0 66 hernia ind ntestmil obstruction (560. 561, 570) 1/1.51 Oastrms. duodentiis. enteritis md colitis (543. 571. 572) 1/1.31 Cirrhosis of liver (5*1) 3/1560 Hyperplasia o( prestate (610) Q.-T) 39 Sy^oioms. ;emlity and ill defined conditions *790-795) < 7 24 :fh*r j`:eases 2: 45 *j V"*:r *:* accidents ;31u335'j 17 32 jt^er at: Cents (800-302. 340 962) *.3 30 54 '.utade 363. 370-979) -itmiode -?S4. 980-985) No. of workers Person-years 16. !6 83 Ml 98 712* 7714* SMB* 75 :9 :o no 139 94 13? 91 30 155 35 :06 '.29 30 " 37 73 35 16 35 ::i 0 54 56 0 71 32 21 0 15 *9 * 56 * 53 4 S * :i2 9 A0k \ I * 5MR's adjusted (or deaths *th cause unknown S inificint 11 5^ 'eve( ^in-scant 31 !* eve* V I no ;n ihe stufiv population as a Abu!** However, in those workers with in 'ii >*t ! 5 or higher, there are IJ oh* *r.*-*i ra>**s where S. 14 are expected i r,ih>* 11 In the 'ubfgroup of the above workers with rive vears or more exptwure. them jtp 11 ob^rv^d r*av^ anti " ~~ "Want'd ^ spir it* *r'. fjnrer 'hn*.vv j vh^hf t*\- - n rhe r.ital ^ntup. anti a similar pat tern Uir i;*rt-r**nt exposure k ju^ories w-.'n j { .*|*srlV'i| It) 2H expected *t t `"'i rhc Exposure* If'<i*^ I 5 ir i * md '2 wb^etMii *i *j0 ^x- .v*'t'n. m addition. ihe duration >i of*'*Mjre \\ tr. e v#*ars tt tnur* 512 Malignant noopla^ms or *ihtr anrl un^pct.:fi(j >:tfs show an .mv-'-n m ?ht? <iral i'roun. aril an im '`d-i' .'.ah both !i".i.'l an. i kiMtion of rxno*.un? (Tabu's 5 and *>) ;hi' mijtton^nip wtth xpo^ure is more pronounced. since rho>e with ex- oi>"um*s .>i |.ns than five v^ars have 'a * `f 'han t m j*d rh#- 'vmphornav ,ur!>n*M?' >* * urnng at about iht1 u-ii mi** wN*n 'ht* whole a* roup is lonsidiTeit. ar** * otv ntralod almost **o*:ri*iv m the h^h -tinNir*1. ioni> iur,it:on ^ruup !n that * ieo;orv io '.u;r t ,1ms <ilr-tTV'*d md * rf4 xpot t*s| Cam ers of the ^vnitjl and urinarv organs, and leukemia, have fewer i ,ms H than expected. The number of rases is too 'tnal! to examine am m-nds Discussion The tavorabie overall mortaiitv oi fh** study population is a phenomenon com monly observed in working populations Standardized Mortality Ratios in the <ow HO's and below have b**en tnund * f Even in uccuoanons with wH! dt-?m**d 4 ha/jnh w hu h rauM* an iinr.-a'iil r:sk intm a >.p,i ifst* i .ui't'. ihn o.i-Mil ''lor Mlilv iii.lv 'lilt !>e MvoiabW' Ins jijm* llv* !ii\v rok from major <a;j'< > a l*aih. Tri'um'nMv in iht* i aniii a .im uMf -- mnjl * ai*s?orv 11 Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw. Gaffey r st *r ) VAB.0001192125 o #%> O Obs.ttp 1U 770.13 nis 0/1 16 37 44 28 3/1 62 7 '2 50 H 13 56 2 2 30 ! 2 07 3 6 57 '. 2 IS 1 3 48 5 3 55 34 120 11 7 14 42 3 3 93 63/73.94 0/4.20 1 5 48 I/! 52 5-5 30 12 21 0/0.39 0.0.88 0/0.76 2,8 90 0 0 25 9 l 22 6MR* 70 " 3 0 90 330 60 r 36 93 51 146 19 31 146 75 ' 52 30 92 0 19 70 0 92 48 0 0 0 23 0 0 I OfeiEip 1 157.195.61 1 0-2.33 | 0/2.18 1 41,1267 0/1 21 12/9.14 i 3/10.28 1,1 43 O'! 52 3.452 21 57 j 5 2 54 1 27 65 59-96 39 6/10.06 2.2 35 51,58 05 1/7.89 2.3 86 2 1 07 J____________________ 0177 | 0/4 13 j 1 1/160 0/0.27 J j | 1 1 1/0 63 1/0.55 1 0.0.14 1.3 09 SUM" 1 60 s |0 10 A 134 141 135 75 0 190 136 1 * fc1 il 55 " 64 75 95 38 56 201 |0 |0 j 68 |0 j 171 1 196 | 16 * J 0 ( 34 ' SVR's ^ tof S ini1*-:art 5% wl *$-iO'r,CJrt! it evei cause unknown In or the**? tact*. SMR's which jrr higher ?han expected may be worthy or attention even if they are not # statistically Mtfmricjnt. This is especially true m th* present study since the num ber ot deaths ;rom manv causes is quae small, and i*n a relatively hnh sMR rnjv nit reach -ratistical significance li. n addition. a narticular cause * shows a < ijnsi.tent pattern of increase With *.()> /sure or -shmatcd exposure, the criW'ns ire oarticuljdv interesting Bv inese < riiena, mortality from dite,rc.e cancer. respiratory cancer an- **r of other and unsjjc- itusj .itcs, and hmphomas. appear to he relawd to mx- po<ure as denned :n this >?udv In view of the association between vinvl chloride exposure and anvtosar(iirna or the Iiv*t. the diiV'siive cancers were examined lurther t > t** what con tribution ani$n>sjrc nma made to the ob served morralitv pattern ('it the t`9 dmestive > jn< ers. seven were liver i jiuks, ot a l'i< h two were arivu)sari ornjs wiordimz io rhe deaih certificate However, amoei* anvio'arc-unj deaths m vinvl ihlonde workers dentified bv other investigators. there wt<re six which occurred in the present study population during the study period. They were all found m rhe course of the study. Table 11 shows these cases with the cause of death as aiven on the death certificate. Note that ne case was certified as cirrhosis, and was v) considered throui^hout this study, since the validity of comparisons with population data required that cause of loath he determined onlv rrom in formation on the death certificate Ihe other live wore correctly classified as Journal of Occupational Medicine/Vol. 16, No. 8/August 1974 513 VAB.0001192126 * fc 2 [ l r r Tabic 6. -- Observed Deaths.ttpected Deaths and Standardized Mortality Ratios in Vinyl Chloride Workers by Duration of Eiposed Employment. Cause of Death with IX.D. No. ObsXxp * (0 months SMR L 60 months Obs tip SMR* All causes Tutrc*001 019' '.te'tuicsis of -esotfrofY wstam C010C3) Mj*>gi'jnt leopusms * [40 2031 Ma* jnjnt lecpmms. Ductal civi:v srtd r"irru '140-18> Vacant lecciasms. lges!:ve ;rgms nd perif:neum [50 159) Mifflin* -^p'jsrfis. **S5 Mt5fv 130 L54i Mangnjnl necotisms. genital organs * I'0*179) Malignant neoplasms, urinary organs (130181) Valiant "!;c!3sms. :ih*r and jnspet'fied n*m.i t'l?0 139) !.euemta and iteukenva 204j Lv^Ohcmjs 200 203. 205) Diabetes meiiilas (260) 94 140 53 M 23 ^* i.OJ*'* 3 : js 4 0 73 2 3 26 5 5 52 3 0 39 a*o 33 : 340 : 125 ] : 20i 1 | 2 I 30 67 ' 0 D j ic8 65 10 0 71 76 50 p j i?4 251 329.30 ^ 3 55 ) 2 ;2 5: 5 7 . 2 .6 17 16 56 :: uii 1 2 76 1 2 79 15 n 2 2 53 5 4 07 5 4 54 76 - * a/ 1 * . <4 .9 47 .35 US r.2 37 187 31 126 113 Maior cardiovascular and renit diseases > 330-334. 400463. 592 594) Vascular Astons affecting CN$ *330 324) Rheumatic fever & chronic rheumatic heart dis *400*402 410 416) Arteriosclerotic heart disease (420) Nonrheumitic endocarditis *421. 422) Hypertensive heart disease (440-443) Other hypertensive disease : 444 447) Chrome & unspecified nephritis & renal sclerosis *592 594) 28 51.45 1 5.97 2 2 39 21 32 54 0*1.79 1.242 0 0 79 9; 155 65 * 81 101 78 T 0 49 0 0 125-157 39 9-18.71 3.4 53 98'ICS 39 1,5.35 2/7 01 3'1 32 02.76 8149* 63 96 20 30 170 0 nftuenza ana pneumonia 450 493) -:cer :t >nd 5-2 ;4 \ < 12.93 1. 1. M J 123 1 2 7 09 1 * 7? - M 29 >7 4;cend<wS -.550-553> 1C 24 3 3 0 43 0 4er"'a and rtesrnil obstruction 560 551 v0: *iistr.vs ojoceniiis. snter,t`s jnd :s*vs -54; 371 5721 Cirrhosis of uver (581) Hyoerotasia of prostate f'510) 3 0 4? : 0 40 ; 149 9 0 07 0 201 26 15 1 \ 10 c 9? ^; n* i *;5a 3 0 33 93 0 18 0 Symptoms, ie.vhty and *tl defined t-n<K ens 1 '30 795) At! ;tt*er Tseases -esiduji) Velar .emete accidents *310 335) ' 2 28 4.*! 97 :d 15:4 t 53 m 40 75 !1 >3 5 09 :t 15 26 34 ' 16 65 0 63 7 43 - icc e*r.! *0010? *4? 362> \:u 963 -'9 3*9) -------: it 254 HO 53V: Ho. M tioii*rs ?inonvears ? 12 ?4 6 9 14 . 5 45 1 2955 24201 55 ' ;:4 :* :: :o *9 : s 2*3 4134 43240 53 ::c \ a 0VR s *of ieaths S int*cjnt at 5^ >*et 3 ^n.Scjiv it 2% **ei :just I u I f I i I Mortality Study of Workers in Manufacture of Vinyl Chioride/Tabershaw, Gaffey VAB.OOOl 192127 A Tible 7. Observed Deathsxpected Deaths and Standardized Mortality Ratios in Vinyl Chloride Workers with Exposure Indices Below 1.5, by Duration M Exposed Employment Cause of Death mth I.C.D. Ra All Causes T-jpefCulcsiS iOO! 019) T,0er:iiicsis of respjra*ery astern *001 008) Mb* ^nant -*oc<asnns '140 205) Mj.:$nam neoplasms, D*-c:al cavity and cf.irvnx '.**} .*i) Malignant neoplasms, digestive orfins and peritoneum 1150 L 59) Malignant neoplasms, respiratory system 060 164) Ms!:piant neoplasms jemtal jrgans 0 70 179) MjxgfUftf necpiasms. urinary crgins 1.130-181) Mj ^nant neoplasms. :ther and unspecified sites . leusemn and aleukemia (204) l/mohom (200 203. 205) Dia&etes metlitus (260) Muor cardiovascular and renal diseases (330-334. 400*466. 592 594) Vascular lesions iffeamg CNS (330-334) Rheumatic fever A chronic rheumatic heart dis. (400 402. 410 416) Arteriosclerotic heart disease (420) Nonrheumatic endocarditis (421.422) Hypertensive heart disease (440443) 3ther hypertensive jisease (444447) "home A unspecified icchntis & rerai :cv:a 552 j-'d sneu^oma <460 493) * 60 Months Exposure Obs Exp SMI* 5619.23 3 : 1: 1J * V> 1 * 3 :2 36 i 0 45 : 3.43 2158 : 0 53 JO 55 : 9 97 0 0 79 0.1 26 2/1 15 21/33.38 2 3.93 2.1 50 16/21 14 3/118 1 ! 58 JO 50 JO 97 : * ?6 53* 9 0 73 1036 34 65 5 o i:o o . 0 203 73 * 59 155 88 0 74 0 3 198 A 60 Months Exposure ObsEip 1 | 132 181.21 1 ! 9 I 97 J 1 45 19.1116 : ii [? 6.-9 08 i 9*10 00 i :i62 ! : 153 j M43 ! M 40 l *2.23 ' 3/2 50 SMr 73* 0 0 ac ++ 38 68 93 57 137 7] 46 + i 24 S3.-S6.82 5/10.51 1/2.49 52/57 87 0/3 02 0/3 90 M 02 0 ! 53 75* 49 f 41 93 0 0 101 3 1 195 bastvns. duodenitis, enteritis and colitis *543. 571. 57?) C.rrusis of fiver (531) M*C<r0:3Sn of prostate *610) Svmpcms. senility and H defined conditions i720 795) Xil leases : res dual) Motor .e?v;!e KC-Cen J10335) 0*"er Kddents '300 202, U9 962) }53 970 979) :54. *30 9*6* flo at Workers Person-years IMR s jO!,,s**d `or deaths nih ;ji.se ^ <i:*'Cjnt it 5 * !evel. -riAi it it `evel n I 2 30 0 0 05 3: i3 1 7 15 ! id; 17 : i :3 -* p +4 J715 21411 12 0 OJ -v u 4 6A '.5 09 0 20 5 2 *9 ' f 37 I 4 ft n : 5 -16 ']t :6 '9 56 33 : 39 ) 2317 23920 Journal of Occupational Medicine/Vol. 16, No. 8/August 1974 515 VAB.OOOl 192128 * I 4 Table S Observed Oeathutxpected Deaths and Standardized Mortality Ratios in Vinyl Chloride Workers with Exposure Indices of 1.5 or Greater, by Duration of Exposed Employment Cause of Death with I.C.D. ft* 40 Causes Tjoerculosis CO l 019) Tuberculosis pf respiratory system (001 DOS) Malignant lecptasms UO 205) Malignant neoplasms, buccal cavity and pharynx (140 M3) Malignant neoplasms, digestive orpns and peritoneum U50-159) Malignant neoplasms, respiratory system (160*164) Malignant icoolasms. genital organs U70-L79) Malignant 'ecplasms. urinary organs (ISO LSI) Malignant -ecoUsms. :ther and unspecified sites (190-199) Leukemia and aleukemia < 204) Lymphomas (200-203. 205) Diabetes melhtus (260) Maior cardiovascular and renal diseases (330-334. 40046ft. 592-594) Vascular lesions affecting CHS (330*334) Rheumatic fever l chronic rheumatic heart dis. (400402. 410416) Arteriosclerotic heart disease (420) Nomheumitic endocarditis (421, 422) Hypertensive heart disease (440-443) Other hypertensive disease (444447) Chfcnic 5 .n<:eci?iid nephritis & renal sclerosis '592 594) ;ifluenn and pieumcma '4S0-493) Ulcer of iiomach and duodenum (540, 541) Appendicitis -550-553) Hernia and ntestinal obstruction (560. 561. 570) Gastritis, duodenitis, enteritis and colitis (543. 571. 572) Cirrhosis of liver fSftl) Hyperplasia of orcstaie (610) Symptoms, senitity and ill-defined conditions (730*795) Ail j:hei : scales esidual) Mct^r <eh*c*e i-;:d?e:s .313 935) -ner ic: cer* i 50 502. 34(3 962) ti :*M -;0 :S5> Ra of ffoners ^erien-Yaari < SO Months Exposure Obifxp SMR* 3ft 47.93 79 ) 0 76 JO 7! 0 0 V6S7 0-0.23 Id 67 i/1.79 O.tJ.29 30 26 ! ] IS 1 0 44 1(0 71 96 0 76 71 0 0 107 2S8 178 0061 0 7(16.54 2/1.87 0.0.82 5/10.41 0,0. >7 0,0.76 0/0 27 0 0 54 54 * 135 0 61 * 0 0 0 0 ] 3 99 3 10 35 362 0/0 OS 0 30 14 0 10.14 904 0/156 0 0.0 01 0 1/0 30 158 J 402 3 7 6 05 Mo i 4 :i i ?40 ; 7 ;a :o; :53 1240 12121 2- OO Months Exposure Obstxp SMI* 119147.11 si * 0/1 57 o-; 4s 3 9 6 26 11 00 99 li/7 47 12,150 11 41 O'l.iS 7151 1/1.13 4/1.84 ML 0 151 144 73 0 204 90 >22 2.2 04 100 62,70 46 4/8.19 22 04 46/47.65 12.32 2/3.10 20 81 0/1.23 90 50 100 98 44 66 253 0 0 3 13 AJ 3d 25 3 OO 19 0 1.0 49 :o9 00 41 0 15 08 20 00.13 3 07 30 5 11 98 0 C j t* ` ? 7 43 .'8 : 7 J6 i 4 62 :s -.3 % + * * 1117 19305 ' 6R \ stli^sr-ed `V :ej:ns i*h :ause unknown 6 gnifitant it 5^ Cv*i *5gn:fican: j! . * <*ei 516 Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw. Gaffey J i i Table 9, -- Other Malignancies (190*199, IX.D.) in VDM Epidemiology Study Population. 1! Study He. 4g at Oeatfa Mas. Etposed Cause as Sim Autopsy l i !56 Widespread metastatic melanoma il yr j Ii Malignant melanoma af back 9 I 50 Malignant melanoma *'tft *despreatf no metis! ases I 2096 57 59 Brain tumor (carcinoma) *J mos, 3945 43 64" Meningitis and pneumonitis (5 wits.) no Eoendymoma. fourth ventricle brain I (2 mos. postop craniotomy) 33 54 31 Astrocytoma, malignannert cereoru hemisphere (1 yr) 4800 61 51 Carcinoma of the brain AO > Arteriosclerosis Pneumonia due to static congestion 7279 57 271 Brim tumor, glioblastoma multiforme (18 mos.) 7300 44 211 Bratn tumor, malignant (2 mos.) 7371 58 249 Brain tumor, malignant no 7306 53 215 Thyroid carcinoma *uh metastises no 1 5'69 52 2J9 Carcinomatosis Carcinoma vertebral body /cs t 5246 57 201 L'.ccsarcoma <th metastasis (3 mos.) yes 7850 64 193 Carcinomatosis, primary region not known (Past history, rheumatoid arthritis, myocardial infarction) no 4778 54 300 Cardiac arrest U hr ) Respiratory arrest and cerebral Hvpona (2 days) Widespread metastatic carcmcma I (2 mos) iI jr*6 61 n13 0*neni;ed meracracis ^rdiHer res I runted '7 mos ) / i. Sduamcus cell carcinoma marv i*!e I 5 .'83 59 * SO Men suite .arr.n ;na ot joocmen 7 C*1 tai r.-e ;oCe*er*r*ed 1* Pulmonary rrznr.tmaj 4 ) 'JO! 55 133 Carcinomatosis *4 -nos) no I\ ?' Tiarf xt j Meter*"! red f i 7 Journal of Occupational Medicine/Vol. 16, No. 8/Ausust 1974 mm rr i n MM A * I a f ai a I aft i P i i ! !i p p 1I 4 ft * f * V^&?0001192130 4 !r.',r ! jrf t*r but univ :vv<i vv tp r** :ti>d .is -ingi< isjrc oi*ia It there had b****n no angu^-m omav hi* number ot dr*a!hs i la*"-.*o1 js orrhosis in this study would have d>'< rMsi*d bv one. and the number i lassiiied as digestive cancer would have decreased by five The pattern of duration and intensity of exposure in these five cases was such that it they had not been present there would have b*en * no relationship between exposure and digestive cancer. The mortality pattern m this cause group is therefore attributable to angiosarcomas of the liver The other cause group worth further investigation is cancer of other and un'}>** itied site<; both because it is a ht-ierofceneous category and because it seems. unlike the other cancers, to be more related to duration than to level of exposures. Table 9 shows a list of the specific causes included in this category, which is essentially brain cancer and generalized cancer with primary site unknown. About 40% of the observed deaths were due to brain cancer. In the general male population, about 22% of this category is due to brain cancer, so that not only is the mortality from cancer of other and unspecified sites excessive, but brain cancer is overrepresented wnhin the category The possibility exists based on the lack of specificity of some of the listed causes that some of the brain cancers were not pmnarv. but metastases from another unidentified site such as the lung. The cancers of the buccal cavity and pharynx are difficult to explain because of their occurrence in the low exposure, short exposure group. It is possible that the. is a chance occurrence, that exp- sijres to other substances were in volved. or that the mouth and pharvnx rr.iv be pec uliarly susceptible? because of ,Ke jMsivhj., nature of the chemiral. Possible Biases in the Calculation of Risk Thf*re are two maior potential sources or hias m the study The first *s that the ri)! w up rati* ;s lower than is desirable fle <.>(ond is that observations of a-.rkor* with long exposures followed hv a long latent period are not d*i|'iJfelv represented, so that the* ''.M'r i pt the study to detect causes of li'iih .issoi :at*`d with long exposure and loi'v* latent v is impaired Populations v;th >;ji h i har.e teroht v exi-a and 518 S5 c 1 O Table Study No. 3023 3431 3001 7365 3354 Meopiasms of Buccal Cavity and Pharyni (140-148. I.C.D.) VCM Epidemiology Study Population. A(t at Death Mov Ei posed Cjus* is Givtn Autopsy 31 CifC nomj it ':p with no io `unf and neck (5 yrs) S6 30 Puimomry edema i SO mm ) no Pulmonary metastases 'Carcinoma, epidermoid, tonfue and mandible) 57 71 Metastatic squamous ceH ca primary 'esion oalate yes w 40 Atetecssis *lue to metastasis res mediastinum i4 mos.) Muitiole malignant metastases to brain. >iver & mediastinum (1 yr) Adenc carcinoma of nasal pharynx t2 /rs ) 63 26 Massive hemorrhage into tracheotree / Status post laryngo-pharyngectomy, eft ridtaf neck dissection Weff-differentiated keratinizing souamous celt carcinoma of left pyriform sinus tmos.) 1 Tabic 11. Angiosarcoma Deaths in VCM Epidemiology Study Population. Stuff Mb. 4250 4255 5755 7303 7376 7385 Age ft bulk 54 50 45 38 52 41 Mm. Eipnd Cause as Given 203 Cirrhosis of liver (sev. weeks) 281 Bleeping from hepatoma (3 Pays) risennecs cirrhosis) :67 Angiosarcoma ri. 'obe of liver v 10 mos.) '.74 liver failure (1 mo.) Cancer of liver, primary (15 mos.) 238 Cardiac tampanade and massive left hemothorax (mins.) Widely metastatic angiosarcoma of liver (4 mos.) 214 Hepatic failure Primary carcinoma liver Auteosy ves r r f*s should he investigated References I t t*xr**r |) ; \ Vj.rn* \\R fr* V< n N* vlr'l I `r4I if1 In ! '*!( s'|f-s it? f'tii'Mf'' IM< * MN ! > . r.! . * S- /'#/ H\ Avu *t / J fs * *" 1 \1af'*N,!ii*r Ml i r\ \ R .* a I H llftaf'.K llaXt< l!v*r .l<s,|i|ris :fl *hf` C' ([Tt jtw, I ' htnrHt*| - i>r. i> ;i j -rk>r^ | ONi > \U'tS \\'"t ht'nst hr M8 .`Ml 1 :*i~* t Kf. i tin r \ <a Mll,ii h :t.i >* * Jb rm >r < !: IV vll .1 r 1 tfVv t'* fiv | ! "* ' r w * *i k * *r *V * * S ( te a V1 v i n . . 1\\ * A/n truj / #v As sr H / t) U) i1'": 4 irI 't |b rt i Pi'' r vp' M) \\\\ #r ll ()* < * j( 1t '|l- J u- I' _ 1? !1 0 * f * * " !II \ l tiflM A\ '( 1 l<K V( h [ * ' * .. t* ^ ^ >| | A r * *> < * r * 1 1 1 ll *i i x i a* * t ' ir M.l . .1 `ivrf in 1 lit * iniii.n f4jfl* * i* t A * 1| 'V . l"t, f,. / < ) 4 un 18 i "jl 1 "> t U *4 W>la PL, r;;puto A On ' fj( rat A'n 'un^v arv b* >rt*s *o * *nv I t hl< *rn U* Caw t*r Rt*\ 11 I1** I Or < i -na^- jmI >jr`*n r^i H*-r.rh Oft: iT>,tl \i- Maneia r*K * r**rif x <Mr\ 'stj***|,| r, | for * Ji a'si,-: r 1 ft ) :.*1 \ t C ?ll *' !** ! 4 ** t* '* II p( hit -T i'l ih7) IJ141 44. *pril S. 1*04 K ( btani^ ^t*livlarri *rrrjf : it >ht* n>*`- aOli*vN*t| liMlh rat<* \ X 1 at 47 (1 **i 1* \I * 1 iU * l*M* t xiiji l\ * pr ***fvV * : : k* -f v t 1/fJ Vfv*/ | 1 J -!** 1 It) M) !. i) m - r s Jij W ( * }* r *v*i h a** v in t >111 il t*v M* * 1 1 1 Vi*-i h * ip< i ( N < i i \ l !<. y < | l\\ 4' ;v fi MV\ I..M4 i 4 t4 m * t r! t!I - I , ' I !r * *!( * '! lA * *f m,,g *r"x l\ : *.n ll sifMiU n*t i| tit sir. > i iM iii ** * H t*fl A i* n / ( )g w/i \Ih/ 14 n ). ? > Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw. Gaffey VAB I A i t I 4% I i i I / i No Wi S. pr(P" Te> res p. sh t'g !a> !a> rh w hi cr ar (* Oi R i* . tv tt *4 % P ft tr