Document 4akxxJBqy7yYkK6dQO9BdoXpx

RECEIVED JUN 1 81980 Shirley D. Conner COVERED BY COPYRIGHT LAW TITLE 17 U. S. CODE. Journal of Occupational Medicine August 1974 Vol. 16 No. 8 Mortality Study of Workers in the Manufacture of Vinyl Chloride and its Polymers* Irving R. Tabershaw, 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 year of occupational ex posure to vinyl chloride before December 31, 1972. demonstrated that cancers of the digestive system (primarily 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.5. male population; and, (3) No deaths identified as angiosarcoma of the liver were found other than those previously identified. This is the first epidemiological study which suggests that in humans vinyl chloride may also be associated with cancer of multiple sites. Do Taberehaw and Gaffey are from Tabershaw-Cooper Ayyociatec Inc.. Suite 308, 6000 Executive Bivd., Rockville, MO 20052 The research on which this report is based was supported by a group of companies engaged in the syn thesis and/or the polymerisation of vinyl chlonde. and administered in Ihetr behalf b* ihe Manufactunng Chemists Association. Journal of Occupational WMieinc/Vol. 16, No. 8August 1974 UCC 041593 509 Vinyl chloride in its manufacture and polymerization has been identified as a narcotizing agent,1 as a liver toxin,2 1 and as a vasospastic agent producing a specific occupational disease, acroosteolysis.* Recently, vinyl chloride has been incriminated as a carcinogen producing in a group of workers engaged in the manufacture of polyvinyl chloride a rare fatal liver tumor, hemangiosarcoma5 Large doses of the chemical in rats reportedly produced cancer of the skin, lung and other organs.4 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 the liver, skin, kidney and other malignant lesions. The present study, however, was not restricted to the conditions and sites 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 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 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 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 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 United States male population particularly those producing the monomer, this determination could be made on the basis of job titles. Usually, however, exposure was a function of both job title and the location of the job in the plant, so that the assessment of ex posure had to be made on a case-bycase basis by plant officials Data were collected for as far back in time as complete records were kept. In most cases this covered the entire history of the plant. In others, records were kept for a fixed period such as a decade. In a few, records were kept for different 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 hygiene and safety personnel in each plant were able to identify certain jobs and 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 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 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 therefore have had jobs in the remote past which involved "low" exposure relative to other |obs at that time, but which might be "high" in comparison with current exposures in the same job. 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, to have had the greatest exposure, while those with low scores will have had the least, even though the true exposure in each group may vary considerably from person to person. The estimated exposure history of each worker was summarized by calculating an Exposure Index (El). This was done by multiplying the number of months on each job by the exposure score, totalling these overall exposed jobs, and dividing by the total number of months of ex posure. 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 mail follow-up and retail credit bureau 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 bom (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 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 a substantial 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 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, there are nevertheless 854 workers with 20 years or more exposure, and 1u40 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 Data Collection In each plant, data were collected for each worker stated by the plant management to have been employed for at least one year in a |ob involving ex posure to vinyl chloride. In some plants, 510 Numbvc Ptrcwl Table 1. -- Follow-up Status ot I3M Vinyl CMoriOa Werkars. Total 3M 100 0 Afivt C7/6 008 Dor* Unknown 352 12SS 4.2 15.0 Doatfc Corffltcato* Aoc'4- Not Ah'*. 321 24 92.7 7.J Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw, Gaffey J ucc 1 041594 and work subst from plicai ship both be e coml Calc Th Stani whic obse to th ma male mort Ta deal I caus calci the wert samr whir In wou state each the r singl whu the prof char whr< SMF serv sign T. wor 1.5 divi half T. SVOI Jou v while tad the >sure in !y from of each ,`ulating is done mhs on dialling lividing of ex on stituted int and deter; direct bureau ie vital cember mplete, e born xit ten follow>ut half xposed though musual history ue that r back p suclOssible stantial new hat traced is conwhom shows xposed ch that almost ed ex- later, rs with i 1640 >ws the of ex oear to the El n Kfi. 4 3 , Gaffey and the duration of exposure, that is workers with a higher El do not differ substantially in duration of exposure rrom those with a lower El One im plication is that in assessing the relation 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 is the ratio of the number of observed deaths in the study population to the number of deaths to be expected in a comparable population of 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, for each of these causes for the total study group. In calculating the SMR's for specific causes, the 24 deaths for which no certificates were found were assumed to have the same cause distnbution 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 study population from the expected value of 100 was tested.1 A single dagger indicates those SMR's w hich 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 S versus those at 1.5 or above. The dividing point of 1.5 represents a level halfway between "low" and "medium." Table 6 shows similar results for workers with less than five years ex Table 2. -- Distribution of Months in Eiposod Cmptoyinant by fur in Which Exposure Bc(>n, for 712S Vinyl Chloritfo Workers eith ComptotoV Follow-op. To/ Eip. 5lrt4 imw 194049 1950 59 1960 69 1970-71 TaM Total 460 35 2 1048 135 1967 389 3368 1714 715 715 7128 2955 60-119 4 93 257 1442 170179 1 119 383 195 Mofithi f Eipwn 110 239 240-299 300-159 4 6 13 151 277 237 631 767 360419 5 34 1796 690 716 565 250 39 Vnknowi 2 20 17 39 posure versus those with five years 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 in 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 by a percentage which varied in each subgroup. Results of Analysis The overall mortality of the study 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, particulariy heart disease, accidents and "other diseases" not detailed in the tables, were significantly below their ex pected values. When the study population is divided according to intensity and duration of exposure (Tables S and 6) and com binations of these measurements (Tables 7 and 8) three ma|or patterns emerge. For malignant neoplasms as a whole, the SMR increases with increasing ex posure, whether measured by level, duration, or both. In the high exposure group with 5 years 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 years exposure. Table 10 is a listing of these deaths with age at death, duration of exposure, and cause as stated on the death certificate. Cancer of the digestive system shows _____ . ......... j Mn r- t 1.0-1.4 t 1.5+ _ IMuon : TaW TiM 1 -- fit. *4 % d 7171 Wnjl CMarMa (tartar* ky Marita tf UfttH Emotaymaot W teum tula. Marita aI bptaa* Tfltri 0c 1 4037 (100) 3057 (100) 39 7170 (100) < 0+ * 1715 (43) 1740 (41) 2955 (41) 00-119 He % 1175 (21) 671 (27) 170-171 0+ * 402 (10) 295 (10) 110-123 ht 406 (10) 310 (17) 240-799 lh t 747 (7) 291 (10) 30W59 Ik % 97 (2) 159 (5) 1796 (It) 697 (10) 700 (11) 565 (1) 81 (4) 360419 ik % 16 (0) 21 (1) 39 (1) ttikmw 39 39 (1) Journal of Occupational MedicitwA/ol. 16, No. 8/August 1974 UCC 041595 511 TiU* 4. -- ObMrwtf DiiHn&ettM D*tb nt Stindirdiind MartalHy Ritito i* i**t CMwM* Warttre. Cats# ef Death with LCJ). Humber Ohi^xp 1 ainn 352467.24 Tuberculosis (001-019) Tuberculosis of respiratory system (001-008) 1/5.71 1/5.34 Malignant neoplasms (140-208) Mjbpent neoplasms, buccal cavity and pharyni (140-141) Malignant neoplasms, digeslive orpins and peritoneum (ISO-159) Malignant neoplasms, respiratory system (160-164) Militant nnlunt. frotil *i*t (170179) Militant Montium. vrimiy vpnt (180-161) Militant nnttiini. otlur md umnwXed lito (190-199) Leubcrmi and iteuhvmia (204) Lymphomas (200-203, 20S) 79/77.16 5/1J4 19/2147 25/23.93 3/3.55 1/340 17/11.73 3/377 6406 Diabetes meNitus (260) 74J1 Mijor emdtawul* ind not Anun (330 334, 400448, 592-594) Vacat* total ilM* CHS (330-334) ttnmitic to* 0 ctwonic nwumMic twnrt On. (400-402. 410410) Artarwsctrutit heart disease (420) NaM-lMMatic HtaarOitts (421, 422) Hyowtmto 4urt OImin (440-443) Otlw htartmin disuw (444447) Cbnmc 4 impieitM wjl'it t iml tUerum (392 594) 155/207.46 v 11/0641 r 54J7 121/13733 . . 1451 1/1.33 3/240 0447 Mlinmi ad oaumnnii (410493) S/9-96 Ulcer of stomach and duodenum (840. 841) 2/3-13 Appendicitis (880-883) 0/0.66 Hernia and intestinal obstruction (560, 861. 570) 1/1-51 Gastritis, duodenitis, enteritis and colitis (843, 571, 872) 1/1.31 Cirrhosis of truer (511) 3/1560 Hyperplasta of prostate (610) 04.39 Symptoms, semtity and id defined eonditmos (780-795) 1/7.34 AA other diseases (residual) 2145.78 Mm* taide kXidtntt (8)0435) 17/32 70 Otlwt Kddcnti (800402, 840-962) 11/1064 Suicide (983, 970-979) 16/1643 Homicide (964. 980 965) 1/11.98 Ntl <f ambers r*x-T<r> 7171 77146 SMt* 75 * : 19 20 110 189 94 117 91 ! 30 158 IS 106 120 d ao ; 57 * : 71 95 16 35 124 D 54 * 86 0 71 82 21 0 15 19 * 56 f 63 * 102 9 *SMR's adiutied for deaths with tme unknown t$tgniftcant It 5% level 'Significant at 1% level no excess in the study population as a whole However, in those workers with an El of 1,5 or higher, there are 12 ob served rases v here CJ.14 are expected (Table 5) In the subgroup of the above workers with five years or more ex posure, there are 11 observed cases and 7 47 expected Respiratory cancer shows a slight ex cess m the total group, and a similar pat tern for different exposure categories, with 13 observed versus 10 28 expected when the Exposure Index is 15 or higher, and 12 observed versus 8.50 ex pected svhen, in addition, the duration of exposure is five years or more 512 Malignant neoplasms of other and un specified sites show an excess in the total group, and an increase with both level and duration of exposure (Tables 5 and 6). The relationship with exposure is more pronounced, since those with ex posures of less than five years have fewer cases than expected The lymphomas, although occurring at about the expected rate when the whole group is considered, are concentrated almost entirely in the high exposure, long duration group. In that category there are four cases observed and 1,84 expected Cancers of the genital and urinary organs, and leukemia, have fewer cases than expected The number of cases is too small to examine any trends Discussion The favorable overall mortality of the study population is a phenomenon com monly observed in working populations Standardized Mortality Ratios in the low 80's and below have been found" 10 Even in occupations with well defined hazards which cause an increased risk from a specific cause, the overall mor tality may still be favorable because of the low risk from other major causes of death, frequently in the cardiovascular -- renal category." Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw, Gaffey ucc 041596 >.1 x- iS'itokH I l * :ases es is if the com mons. ; low d. 10 fined j risk morise of ,es of icular Gaffey TiMo 1 -- ObtorooR Dcithi/tipwtctf Dtitlu and SUndirdiMd Mortality Ratio* in Vinyl Chloride Workirj, by Estimated Uitl of Eipoiore. Cum at Ooeth with LC D. No. | n * t,s tl 1.5 Obi/Elp SMR* Obifrp SMR* lit Causes 1 fit770.33 70 * t$7/l$S.tl 60 * Tuberculosis (001019) Tuberculosis of respiratory system (001-000) 0/3 38 0/316 0 0/2.33 0 0/218 0 0 Malignant neoplasms (14Q-205) Malignant neoplasms, buccal cavity and pharynx (140-148) Malignant neoplasms, dttwtite organs and peritoneum (150-159) Malignant neoplasms. respiratory system (160-164) Malignant neoplasms, genital organs (170-179) MilitMnt neoUim. uririit- orpin (180-181) Malignant neoplasms, other end unspecified sites (190-199) Leukemia and aleukemia (204) lyiephomoi (200 203, 205) 37/4428 5/162 7/12 50 11/13.50 2/2.30 1/2-07 9/5.57 1/2.11 1/3.46 90 330 60 * 86 93 51 146 49 31 41,12 67 0/1 21 12114 13/10.28 1/1.43 0-rl 52 8/4 52 2,157 52 54 134 0 141 135 75 0 190 136 212 Diabetes methtm (260) 5/1.65 146 2/2.65 ftl Major cardiovascular and renal diseases (330 334, 400-468, 592-594) Vascular lesions affactint CHS (330*334) RbHiMtK tMT 4 throoit rheueiitic dot Oil (400-402. 410416) Artorwrtrtotie Sort OiMitt (420) Honrhiumatk endocarditis (421, 422) HyoertOhfwc burl dtsou (440443) Qtta hypeittisne disease (464-447) Chrome t iuu|ieo6ed ooohritio t rnal ockruii (512 504) 84/1249.11 7/14.42 3/1.91 64/70-04 0/420 1/5.46 1/1-52 0/2.50 75 * 52 * 60 92 0 19 70 0 mm 6A0.06 2/245 51/51.05 1/2.19 2/3.16 21.07 01.77 85 + 64 75 95 36 56 201 0 InOwat Mb onumoni (460413) S/9.80 02 0/4 U 0 Wear of ttonwfa and duodenum (540, 541) 1/2.21 48 11.60 61 AwmOiotii (550-553) o/tuo 0 0/0.27 6 Hernia md tntatmal obttnictnn (510, 561, 570) 0/086 0 1/0.53 171 Gastritis, duodenitis, enteritis and coUtts (543, 571. 572) OR). 76 0 1.055 196 Cirrhosis ol liver (581) 2/190 23 1/6.64 16 Hfftrplnii <t pronto (610) QRL25 0 0/0.14 0 lyieetoeH. nMy ood iH4efc*l conditioin (710-205) 0/1.22 0 1/309 34 M other 4iHUn (rtudul) 14/21.90 66 * 613.60 41 * Motor *ebtdt onrOoirtt 010435) 6/19.01 45* 013.46 72 Other Mddooti (600402. 640-062) 11/17.63 06 7 612.67 50* SwoOt (061, 974070) 0/0.73 06 7/7.02 107 - Hoard* (064, 060-065) M.98 0 1/4.M 21 He* etf workers 4432 45134 1457 32106 ` SMTs MyntfO Ik. dsotha dtb caosa oohoooo rS*kmt at Hat SiftiOeut SUM In view of these bets, SMR*s which are higher than expected may be worthy of attention even if they are not statistically significant. This is especially true in the present study since the num ber of deaths from many causes is quite small, and even a relatively high SMR may not reach statistical significance. If. in addition, a particular cause shows a consistent pattern of increase `v*th exposure or estimated exposure, he findings are particularly interesting. 8y these criteria, mortality from d'gestive cancer, respiratory cancer, can- cer of other and unspecified sites, and lymphomas, appear to be related to ex posure as defined in this study. In view of the association between vinyl chloride exposure and angiosar coma of the liver, the digestive cancers were examined further to see what con tribution angiosarcoma made to the ob served mortality pattern. Of the 19 digestive cancers, seven were liver cancers, of which two were angiosarcomas according to the death certificate. However, among angiosar coma deaths in vinyl chloride workers identified by other investigators, there were six which occurred in the present study population during the study period. They were all found in the course of the study. Table 11 shows these cases with the cause of death as given on the death certificate. Note that one case was certified as cirrhosis, and was so considered throughout this study, since the validity of comparisons with population data required that cause of death be determined only from in formation on the death certificate. The other five were correctly classified as Journal of Occupational Medicine/Vol. 16, No. 8/August 1974 i ucc 041597 513 Tabla i. -- Otuaraad DaitlntipatM Otllhs and stindifdind Mortality Ratios i* Vinyl CMoriOo Wortton b| Dutaiian l Expmad Emptoyaaiit Cai Daato mM LC.D. Na. 60 maatha OHtip SMR* 60 amt* Obrfip SMR* Ml causes 94/140.53 07* 251/329.30 76 i labercutoan (001019) Tuberculosis of respiratory system (001-008) 0/2.23 0/2.07 0 0/3.55 0 0/3.33 0 0 Malignant neoplasms (140 205) Malignant neoplasms. buccsl cavity and pharyni <140141) Malignant neoplasms, digestive organs and peritoneum (150-159) Malignant neoplasms, respiratory system (160-164) Metignant neoplasms, genital organs (170179) Malignant neoplasms, urinary organs (180-181) Metignant neoplasms, other and unspecified tries (190199) Leahema and aleukemia (204) Lynplumu (200203, 209) 11/19.96 (70.76 279.26 3/5.52 0899 0/0.13 2/3.40 1/129 1/2.01 71 6947.61 681 1/2.16 46 17/1696 65 21/11.51 0 1/2.76 0 1/2.70 71 114.23 M 2/2.53 <0 58.07 116 47 106 116 112 37 187 81 126 DiaOatw mallitas (260) 2/1.90 134 58.54 113 Mats cardiovascular and renal dtn*s*t (330 314. 400-463. 592 594) Vascular lesions affecting CflS (330-334) Rheumatic fever i chrome rheumatic heart dis (400-402, 410416) Artermaderotic heart disuse (420) HonrheumtHc endocarditis (421, 422) Hypertensive heart disease (440443) Other hypertensive disease (444447) Chrome 6 unspecified nephritis 6 renal sclerosis (592-594) 20/9149 4/9.97 2/239 21/32.54 0/1.79 1/242 08.79 0/1.55 B 81 101 71 * 0 49 0 0 125/157.39 9/16.71 34.53 98/105.39 1/5.35 2/7.01 1/1.62 0/2.75 ii* 49* 68 96 20 30 170 0 Influenza and pneumonia (410-493) 3/2.93 123 2/7.09 29 Ulcer of stomach snd duodenum (540. 541) 1/107 112 1/2.78 37 AppMdicih] (990 993) 08.24 0 0/043 0 Hernia and intestinal obstruction (560, 561. 570) 0842 0 1/1.10 93 Gastritis, duodenitis, enteritis and cohtis (543. 571, 572) 1840 301 0892 0 Cirrhosis of kver (561) 1849 26 2/1110 18 Nyptipluii of prostiti (6(0) 08.07 0 0/0 33 0 Symptoms, sembty and ill-deSned conditions (710-795) 1/2.2S 93 0/5.09 0 Ml other diseases (residual) 4/11.97 40 16/2634 63 + Motor aoMcIo aeadaatt (610139) 10/16.14 75 7/16.65 43* Otoor tccidwu (000.102. 840 062) 7/1294 65 + 10/17.82 56 + Suicide (963. 9)0 979) 68.34 114 10/10 26 too Homicide (964. 900 989) Ilk of Marhert Person-years 1/5.80 2955 34201 20 0820 4134 43240 0 * SMR's adjusted ter deaths with emu unknown. : Significant at 5% level. Significant it W level 514 Mortality Study of Workers in Manufacture of Vinyl CIUoride/Tabershaw, Gaffey Ucc 041598 -a W til L i i Vpfc t* i i Table 7. -- Obtained Deetlu/Eepected Deaths and Standaidiied Mortality Katin id Vinyl CMutide Vftwktts with Exposure indicts Below 1.5, by Duration of Exposed Employment. CauU f Oeeth with LC.ft. N All Causes rutrtrcutoiiJ (001019) Tuberculosis of respiratory system (001-008) Malignant neoplesms (140-205) Malignant neoplasms. buccal cavity Md pharynx (140-148) Malignant neoplasm*. digestive organ* end peritoneum <180-159) Malignant neoplasms, respiratory system 080-184) Maiipiant neoplasms, lanital upas (170 170) Malignant neoplasms, unitary organs (180-Itl) MiMpaot neoplasms, other end unspecified rin (190199) Leukemia and aleukemia (204) lymphomas (200 203, 205) Diabetes mellitirs (260) Map* cardiovascular and renal diseases (330-334, 400481, 592 594) Vascular tames aflectmt CN$ (330-334) Rheumatic fever 6 chronic rheumatic heart dit. (400-402, 410418) Arteriosclerotic heart ditease (420) Nonrheumatic endocarditis (421,422) Hypertensive heart disease (440443) Othar hypefteniivt diseest (444447) Chrome 8 unspecified nephritis 8 renal sderosn (592-594) Influents and pneumonia (480493) Ulcer ef stomach and duodenum (540. 541) Appendicitis (550-553) Hernia and intestinal obstruction (550. 551. 570) Gastritis, duodenitis, antritis and coMta* (543, 571. 572) Cirrhosis id hwr (551) Hyperplesii ef prostata (610) Symptoms, semhty and iMefined randWaw (710795) *d athai diataaes (rdual) Muter uelMdt acCntwu (S1M35) ' Otlw acodems (H0402. I4-M2) Smddt <943. 570-575) Heunoda <544, 5H 505) u. 4 Merten Rstiueyia * 80 Months Exposure OktCap SMR* 58,89.23 0/1.41 0/1.11 8/12.86 4)0.45 1/3.43 2/3.51 0/0.5! 04)55 1/057 Ofl.79 0/1.25 2/1.15 21/33 35 2/353 2A,50 15/21.14 0A.18 1/1.55 041.50 0/0.57 3/155 041.51 041.16 0/0.27 0,5-25 1/2.50 OuO.Ofi 0/143 4/7.45 3/5.57 3/7.55 3/405 0/355 63* 0 0 73 1036 34 65 0 0 120 0 0 203 73 * 59 155 88 0 74 0 0 188 0 0 0 0 42 0 0 63 35 44 86 0 1715 21411 2. 40 Months Exposure ObsEip SMt" 13ZA8U8 0.197 0/1 85 29/31 46 1/117 5/504 9/1000 2/1.52 1/1.53 5/4.43 1/1.40 1/2.23 3.260 63,05.82 5/10(51 1/2.45 52/57.57 073.02 0/3.90 1/1.02 0/1.53 2/395 1/1.53 0/0.24 0/061 0/0.51 lfi.09 0/0,20 0/2.79 10/12.82 5/922 8/585 6/565 0/343 73* 0 0 96 83 68 93 127 67 147 73 46 124 75* 45 + 41 93 Q 0 101 0 53 67 0 0 0 16 0 0 79 55 83 105 0 2317 23525 'SMR's adjusted doe deaths ante cause uehoowe. `SemSoel at 5% leael -SipiiflcMit at 11 leual <. Gaffey { Journal of Occupational Medicine/Vol. 16, No. 8/August 1974 ucc 041$99 515 TiM* 1 -- OfeinrwO Dutttt/tie<cM Dutfes IN Styndardin* Mortality ItiUn in Vinyl CMoriOo fftrktrs witti EipoMro Micm of 1.5 or Grootor, fey thirttioo ot itpmti Empioynnnt. Coow M Dwife *M LCD. No. M Cwm Ttibtfotknit (001-019) Tnfewcutosi* ol rprrhir lyMm (001-000) MMipiiit MOOlOMw (140-209) Uahtnwt oooplMino, feocnl cmtr aftl pfearym (140-141) MrtpMt unoiaMo, yjyntiw oryan aoO onilonwn (150-1S9) Uotifunt mooMmm, lonirotory syiliin (1601(4) Mtifwuat HoytaHin, fM/tal orpos (170179) MllifikMt MoptiHis, urtalry r|W (180*111) MoKyoMt nioolMm. oHior an4 MMCiW Mot (190199) ikmii w4 ilrulmiiii (104) LympfeMM (100-20). 205) DiifeoM moOitM (260) Major cariumwitir m4 rwal tann (3301)4. 400-466. 691694) VaoiUr low Mhctioy CHS (3)0)34) HwnnXic few 6 chronic rhwaMK haort dis. (400402. 410416) attVHUdtrMK (art 4nm (420) Nonrheumitic endocarditis (421, 422) Hyyrrtinvn Intrt fimr (440443) Other hflrtrtrttiw dtaeau (444447) Chronic 6 annaciM naohritH 6 rtnM kMioss (692-594) tafhMMi *d pwetmMti (440493) Uk* or ilonudi and duodtnwn (640. 641) Appeodicttis (550453) Hirma ind mtotMil obstruction (560. 501. 570) Gnlritts, duodenitis, entente md cdWh (543. 571. 572) Cvrfeni ol few (681) ttyptrplisti of prutite (010) Symptoms, SMftty *ed itt dilned conditions (Tift795) M art* dutaiti (rtudul) Motor whicta students (010435) Othar icodrntj (600002. 140162) Sutode (903, 970 979) Homodi (964. 9S0966) N*. of Norhofi Pmeoo-Yoari <00 Mwtfcs tipiiort Mn SMI* 3147.93 79 0*1.76 04.71 0 0 6A.67 04.23 m.67 1/1.79 *129 MM 1/118 14.44 14.71 04 0 71 71 0 0 107 201 171 (Mil 7/16.54 2/1J7 M.I2 5/10.41 M.57 0/0 76 04.27 04.54 0 54* 136 0 61* 0 0 0 0 04.99 0 1/0)6 302 0/0.06 0 04.14 0 1*1.14 904 o/iii 0 0*1.01 0 1/0.10 158 0/4.02 0 7/0.05 4/4.73 140 107 3/2.40 16) 1/2.10 69 1240 12120 1M Months Ciptwri (to/t'P SMT 115/147.11 iif 0/1.57 0/1.40 36/26.11 04.99 11/7.47 12/0.60 1/1.41 0/126 7/3.51 1/1.13 4A.84 2/204 0 0 141 0 151 144 73 0 204 . 90 222 100 02/70.46 44.19 2/2.04 46/47.65 1/2.32 2/310 24.81 0/1.23 90 60 100 06 44 66 253 0 0/3.13 0 0/1-25 0/0.19 1*1.49 04.41 0 0 209 0 1/5 08 20 0*1.13 0/2-30 0/11.88 0 0 51* 2/7 43 2/7.96 4/4 62 28 26 88 0/2.76 0 1112 19306 `SKR i idtvsted tar deaths with cause ufttaown. fSifntfiCMt it 5% level iStahilcMt it 1% level 516 Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw, Gaffey UCC iLLA3*3_lL 1-- L&otTX %\x V Sluts Ik 2744 3700 2096 SMS 44)3 4400 727) 7300 7371 7300 S7S3 5240 2050 4771 4711 5713 7301 TtMt 1 -- Otkci Mili(iunun (150-1M, I.C.D.) in VDM Epilemiolon StnOy Populstta. Alt it DatM Mm. lspo**t Cnm u cm 31 in Wittspfttl mttaititic iMUiwmt (1 *f) Mtlipiml mtlMomt <1 luck 41 50 Malipint meta*omi with widespread metistiset B? 49 Brut tumor (ctfcMni) (1 ms.) 43 44 MsBintitn Ml pmumMitil (5 *k) Cpaitsmomi. hwtk ttutnckOnn (2 IMS. posiot CIMiotomy) 34 ti Astrocytoma, MatifiairtM cental hemispMre (1 yr.) 01 51 Circimm at tkt brut Aitvindannit PlMtlMMU 1m It stoic COnfHtiM 57 271 Brut turn. pieMatoiu nultiftriM (II IMS.) 44 211 Brut turns, mtAfnitl (2 mm.) 51 24) Brito tvmor, matitnant 53 210 nijicil arduous wit* mst*st*sts 52 23) CarcwoiMWw Cardnoma vertebral body 47 201 Upaureoma witii metastasis <3 ftu.) 44 1)3 CvcimuMt, pnmtty r*|W0 Ml Mom (lot Mors. rimmMtil irtiritit, myOCIflMl itttreUgt) 54 300 Cttlite trnst (1 As.) ' A*lpirlty srrtst Ml cmOrM hyposii (2 IMS) URMsprtil mtttstiUe ctrajntm (2 IMS.) II 311 Gawtlinl M*st*sis untHMsMittal (7 ms.) Summons mN CSsritMIS. ptimtry sits unKtstniml 49 lM MttssMic gratis gl sOlmis CriticM silt MtstviiiiMt (PulmOMry toptipscm) 55 133 CvuMmtais (4 ms.) Pfimtty silt uoOrtrriuistt Itisosy m m m m no IM m m i* m IH m Journal o( Occupational Medicine/Vol. 16, No. 8/August 1974 UCC 041601 517 ivor cancer, but only two were specified as angiosarcoma If there had been no angiosarcomas, the number of deaths classified as cirrhosis in this study would have decreased by one. and the number classified as digestive cancer would have decreased by five The pattern of duration and intensity of exposure m rliese five cases was such (hat if they had not been present there would have been no relationship between exposure and digestive cancer The mortality pattern in this cause group is therefore attributable to angiosarcomas of the liver. The other cause group worth further investigation is cancer of other and un specified sites, both because it is a heterogeneous 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 within the category The possibility exists based on the lack of sixicificity of some of the listed causes that some of the brain cancers were not primaiy, 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 this is a chance occurrence, that ex posures to other substances were in volved, or that the mouth and pharynx may tie peculiarly susceptible because of the gaseous nature of (lie chemical. Possible Biases in the Calculation of Risk There are two ma|or potential sources of bias in the study The first is that the follow-up rate is lower than is desirable, (he second is thal observations of workers witfi long exposures followed by a long latent period am not adequately represented, so that the power of the study to detect causes of death associated with long exposure and long latency is impaired Populations with su< h i haracteristics exist and Tablt 10. Maliynant Nooptasmi of Buccal Canity and Pluryiii (140-141, LCD.) in tfCM Epidomiolofy Study PapulitiHL St4j Ril All at Daath *H Ciboaad bus* is Gta* 3003 31 3431 55 300 L 57 7365 54 33S4 (3 49 Caremom* of lip with metastasis to W*| art nock <6 yrs) 30 futnxmaiy adtma (50 mm) hs(money Mtaitnss (Clionww. ayjdarnioid. tontM and mandible) 71 HaMatic aoumout cod ca yrinacy taann batata 40 MUM dim to motattam to madiastmoin (4 mot.) Wiittipli meji^ml nMostatot to bran. Inor 4 moditstHwm (I yr) AOanocarooama of oaoal ykaiyoi (2 yea.) 26 Unsnt hwrrhip urto tracJ*o4r* SMn post (anwvo-ptaryofactomt. Ml nM oort fawtfwo MHOHIMM MfOOMINIf mwm ClR of Ml pfrilinft thioi {mot) 0 00 yn yn yn Tibia It. -- bntiosateomi Daattn in KW EyiaawMny Study Populatim. Study U 4250 42SS 5765 3303 7376 7345 *(a at Dm!* 54 00 45 3S 52 43 mh im>* Coho oo Ciooa 203 Crrtous of Row (set. worts) 261 ItaodMf troa hepatoma (3 days) (Uoomcs orrhws) 107 taeostnomo iL Mo d knot (10 mot) 174 Low Mon (1 on.) Coacor 0( that, piimiij (15 mos.) 230 Catdac taaoanada and massm lab bamotliorn (mins.) Widody ootaslatK aatmarcoma al that (4 mao.) 214 H^ilic Mvrt Primary urdnoma Voir 5wt*P*y yn JOS yn. yn should be investigated References 1. Lester 15. Creenfierg LA, Adams WR Ef fects of single and repeated ex|ic>surps of humans and rats lo vim I chloride Am /nr/ Hyn Assoc I 24 265-75 196!. 2, Marsleller HI. Lclbach WK. Muller R. el ah (Chronic toxic liver leunns in the PVC (polyvinyl chlondei -- producing workers J Orsc/i Met/ Wnchemchr 98 2311-14. 1973 3 Kramer CC, Mutchlcr IE The correlation of clinical and environmental measurements lor workers exposed in urnl chloride Am Ind HyK Assoc / 33 14 3/1 1472 4 Dodson V\\ Dinman Bt), VVhitelviuse WM el al Qirupaiional acroosieolvsis III A clinical study Arch Em iron Hlth 22 8191, 1971 5 Creech II, lohnson M's Angiosarcoma of liver in ihe inangne, lure of fiolyvinyl chloride I Occup Med 16 I5CI-5! 1974 6 Viola PL. Bigotti A, Cuputo A Onceogenic response or rat skin, lungs, and bones lo vinyl chloride Cancer Res 31.516-22, 1971 7 Occupational Safety and Health Ad ministration Occupational Safety and Health Standards, Emergency Temporary Standard for Exposure to Vinyl Chloride. Federal Register 39 (67) 12342-44, April 5, 1974. 8 Chiang CL1 Standaid error of the age adiusted death rate. Vita/ Statistics Special Re/xiffs, *7 (1961) pp 27S-285 9 Lloyd |\V. Ciocco A Long-term mortality sludy o( steelworkers, I Methodology / Occup Med 11 224-110. 1969 10. rabershaw.Cooper Associates. Inc . unixiblished. 11, Redmond CK, Ciocco A, Lloyd |W, Rush MW Long-term mortality study of steelworkers |v Mortality from malignant neoplasms among coke oven workers. I Occup Med 14.621-629. 1972. 518 Mortality Study of Workers in Manufacture of Vinyl Chloride/Tabershaw, Gaffey ucc 041602 Pc N Nor Will S. P. prot (PTC Teflc respr polyi Ham shive tight lastir lassit with the > with both char; and coun piere Repi Th deso 1972 it is yvom posts to S from tinge f Tin Mr Pjlhtt H fly Kf'| Cell,., H K*4 Jourt-