Document DMbBm6NYVy6anNLk6g84wLVYa

Mortality, Among Employees of PVC Fabricators Leonard Chiazze, Jr., Sc.I).; William E. Nichols, Ph.D.; and Otto Wong, Sc.D. A cross-sectional mortalit study of 4,341 deaths occurring among current and former mployees of 17 PVC fabricators during 1964-1973 is presented. The objectives are: (1) to iden tify any angiosarcoma deatf s among the employees of these fabricators, and (2) to exan ine the distribution of deaths by cause. No angiosarcoma de, ths were found among the study group. Sex-race-cause-speci ic Proportionate Mortality Ratios (PMR's) were computed, u ng the corresponding U.S. mor tality as the standard. Amor g white employees, there appears to be an excess in total cai cer mortality, particularly that of the digestive system. Observed deaths were found to exceed the expected in cancers of the breast and urinary organs among white females. Deficit mortality was observed in cirrhosis of liver among t oth male and female white em ployees. The January 1974 discltjsure of three deaths from angiosarcoma of the liver in a sinlg 2 vinyl chloride polymerization plant and the attention focused 1 this new occupational disease are well known. A significant an ount of information from animal experimentation and observatic n on humans engaged in the production of vinyl chloride follow < d 1 However, there was no information regarding the possible a> verse effects on employees engaged in polyvinyl chloride (PVC) f brication, where potential exposures were thought to be low and to result from the release of unreacted monomer trapped in the resin. This issue was considered of great import because of the ^ery large number of workers believed to be engaged in fabricaCic n In March 1974, represen ta lives of PVC producers, who are members of the Organizatir n Resources Counselors (ORG, Occupational Safety and Heal h Standards Croup, contacted ORC about the feasibility of a stu iy of health risks to employees working with vinyl chloride and Dolyvinyl chloride. Since the National Institute for Occupational afety and Health (NIOSH) was conducting a study of vinyi chib ride and resin producing employees, the scope of the proposed C RC study was limited to employees of From the Division of Biostatistic and Epidemiology. Department of Community Medicine and International Health Georgetown University School of Medicine, Washington. DC 20007 (Drs. Chia and Wongl and Organization fiesouces Counselors. Inc., Washington, DC 200CK (Dr. Nicholsl. companies engaged in the fabrication of PVC resin into finished products. A number of alternative study designs was considered, and it was decided that a proportional mortality study would best meet the urgent need for information. The study concentrated on deaths occurring during the ten-year period 1964-1973 among ac tive fabricating employees plus retirees. Since it was not possible to identify those employees with only vinyl chloride exposure, the study focused on deceased employees who worked anywhere in those plants where PVC fabrication was carried on. The primary objective of the study was to determine whether or not any angio sarcoma deaths had occurred among employees of the fabricators under study, A secondary objective was to examine the distribu tion of all deaths by cause. The relatively few producers of vinyl chloride monomer and of PVC resin are generally medium to large companies, PVC fabri cators, however, range from large plants of major companies to very small job shops. Even in a large plant, there may be few em ployees who are in the vicinity of PVC resins. The range of com pany plant size and number of exposed employees help to explain the wide range of estimates of total employment dependent upon PVC resins. Fabrication is geographically disbursed, with at least some operation in almost every state. Typical fabrication products include coated wire, upholstery fabrics, floor and wall coverings, pipe and other construction materials, toys, recreational equip ment, phonograph records, containers and container lining, and a myriad of novelty items. Since the fabrication of PVC resin into finished products is often a part of diversified product lines in a plant, raw materials other than resin are utilized. Thus, employees may be exposed to toxic agents other than vinyl chloride. Conse quently, in the current study, it is not possible to isolate only the effect of vinyl chloride. Some departures from expectation may be due to exposures to vinyl chloride, to one or more other agents, to some combination, or to employee characteristics other than occupation. Materials and Methods The decision to focus on a cross-sectional mortality study rather than on an historical cohort study derived from several con siderations. First, the primary study objective was to determine relatively quickly whether or not any angiosarcoma deaths could be identified among the study group, and this was best ac complished by examining causes of death among relatively recent Reprinted from Journal of Occupational Medicii September. 1977. Volume 19. No 9 pp. 623-628 0001-Q 26 SAl- fi.e.. past ten years) decadents. The desirability of identifying an historical cohort for folio v-up was recognized, but it was deter mined that it would not ge possible to identity clearly and com pletely the necessary coh >rt of workers within a reasonable period of time, if at ail. As a con equence, this study is based upon 4.341 deaths which occurred during the period 1964-1973 among current or former emplc rees of 17 companies engaged in PVC fabrication. A total of 5: plants supplied data on all identifiable deaths since, as was men ioned earlier, it was not possible to identify those employees wi h only vinyl chloride exposure for the studv. In order to be include f in this study, a deceased employee fell into one of the followinii categories: !1! employee died while actively employed, <21 emi >loyee died after retiring from the companv with retirement b<nefits, and (3) employee died after ter minating employment b it with vesting in a company-sponsored life insurance plan. Dea hs occurring among former employees with less than the numb' r of years necessary for insurance vesting were not included in pkint records and were, therefore, not available for this study An attempt was mad to compensate for at least some of the "leakage" due to emplo' ees leaving the industry prior to the time they were vested in any insurance program by using the following procedures. Once deatf records for a given company were identified, death certificates were obtained and separated into two groups as follows: (1) al deaths with cancer HCDA 140-205 up to 1967; ICDA 140-209 for 1968 on), or liver disease (ICDA 580-586 up to 1967; ICDA 570- 76 for 1968 on), or suspected liver condition mentioned on th death certificate; and (21 all deaths from causes other than cam er or liver disease. Death records men tioning cancer or liver disease and giving a hospital as place of death were segregated ind sorted by hospital. Where there were several death records f >r a single hospital or several hospitals in the same area, arranger lents were made for a Registered Records Administrator (RRA1 to 'isit the hospitals, review medical records, contact the hospital pa hologist and review pathology records to determine whether th* re were any angiosarcoma cases in the hospital's pathology rec ords. If so, an attempt was made to deter mine whether or not tie angiosarcoma possibly could be related to vinyl chloride expos jre. This procedure enabled us to identify whether any employee:, who had left the industry prior to vesting in an insurance program and remained in the local area, had died from angiosarcoma of the liver. The hospital inquiry procedures turned up five deaths ft am angiosarcoma of the liver; according to company employment records, none were employed at any time in PVC fabricating pla ts. These deaths were reported to OSHA. NlOSH, and CDC for nclusion in the nationwide angiosarcoma survey. Death certificates ndt mentioning a hospital as a place of death required an additional step to determine whether death occurred in a hospital or if a recent hospitalization had occurred prior to death. The certifying physician was queried by mail for in formation on recent h ispitalization of the decedent and whether there was any indicatu n that he or she had cancer or liver disease. Additionally identifier hospitals were contacted as above. Originally, it was pUnned that death certificates would be ob tained from life insura ice carriers. In practice, both company and life insurance records vere used because of record retention prac tices and retrieval pro ilems in the insurance carriers. All available death certificates wer; examined by a trained nosologist for men tion of angiosarcoma anywhere on the certificate, and no angio--sarcomas were found on the death certificates. Underlying cause of death was classified according to the eighth revision of the In ternational Classification of Diseases.: Over the ten-year period under study, plant size was found to have changed drastically in many cases. In one instance, a plant employing 300 employees in 1973 employed fewer than 10 m 1964. At the other extreme, one.plant employing 5.000 people in 1964 had only 2,000 in 1973. Some companies had gone out of business. Such developments show not only the rapid changes taking place but also the difficulty of determining average industry employment. The 17 companies covered in this report ranged from single plant, small companies 'one with 70 employees) to multiplant large companies lone with over 7,000 employees). Average number of employees clustered between 300 and 500. Although total employment is difficult to determine precisely, it is estimated to have been between 65,000 and 70,000 at the end of 1973. Since the population at risk could not be determined; mortality rates as measures of risk could not be calculated. Rather, results were summarized in terms of Proportionate Mortality Ratios (?MR) adjusted for the age distribution of the study group. The'PMR uses relative frequencies of specific causes of death by age in a com parison population to obtain expected numbers of deaths from that cause in the study population. Selection of an appropriate comparison population poses some difficulties since it would be desirable to have a cause of death distribution for a similar group of workers dying during the same period, but not subjected*to the factor under study. But such a comparison population was not available, and the study used mortality for the United States, specific for color and sex, for comparative purposes.1 Despite recognized deficiencies, the PMR can provide clues on unusual distributions of causes of death where true rates cannot be calculated. Results Table 1 gives the distribution of deaths among the employees of the 17 PVC fabricators within each of the ten years. An increase in the proportion of deaths taking place in later years of the decade may reflect a variety of factors, such as an increasing employee population, less complete availability of records for earlier years fe.g., in one company, there were no records for the first four of the ten years), increase in duration of exposure, etc. However, there is no reason to believe that any unavailable death records for earlier years would be concentrated in a few causes and thereby bias the distribution of deaths for those years. Tafate l. -- Dktritatfoff of Pm1I WC Nbrtarion 1* VMr.of " Ymt of Oootfc'S- 1964 * 1 " ' v ST* 325 * 390 -i " . `345v 1966 * ' 1967 H 429 1968 1969 ''' ' ' ' 1971-"' " ' ' <99*. /nulls ' ''v' riiS^ioF-7:r7rT^ *15 L. 1 ---Wi 2v, 47'r*:` *tf' ;1! -f- Tsj' 'V-vV;v 430 x y-.?j SAL 000102690 TaMo t -- Dtetrl wtien of Deaths Among Employees of 17 PVC Fobrica on by Color and Sax, 1964*1973. Race Total White Nonwtnle Unknown fc&r1- Tati EV. Ie- 43C 7"'-, 384 2C 2S 1 Matt 3676 3243 380 248 s" Female 663 601 24 38 Unknown 2 0 0 2 The distribution of dea hs in the study group by race and sex is given in Table 2. Most deaths 164,7%) occurred among males. The vast majority (88.7%) of c ecedents were white and there were 288 (6.6%) for whom race coi Id not be determined. Table 5 shows this distribution of deaths b ' age. For both whtte male and white female employees, more than half of the deaths occurred among those aged 65 and ove (58.1% and 51.9% for white men and white women. respecti\ ely). The corresponding proportions of deaths which occurrec after age 65 in the United States population in 1968 were 59% and 72%, respectively). The higher proportion of deaths ar i ong white women over 65 in the U.S. population compared tc the employee population may indicate that relatively fewer wor )en work to retirement age than do men. While the numbers of df aths among nonwhite employees are too small for any definite c inclusions, the distribution of deaths by age among nonwhite m ;n is roughly comparable to that tor the total United States Tables 4 and 5 show the distribution of deaths for selected causes by sex for whit js and nonwhites, respectively. Among white men, nearly 60% of the deaths are from diseases of the cir culatory system (ICDA 390-458) and 20% are deaths from cancer (ICDA 140-209). The cor responding percentages for the total U.S. population of white mal s in 1968 (midpoint of the study period) were 54% for diseases o the circulatory system and 16% for can cer. Digestive and respiratory cancers account for somewhat less than two-thirds of all ca icer deaths among the white males in the study group as compa ed to about 59% of all cancer deaths among U.S. white male: in 1968. For white women, over 46% of the deaths are from dis< ases of the circulatory system (compared to 57% for all U.S. white women in 1968), and 30% were from cancer (compared to 181 for all U.S. white women in 1968). Somewhat over half of t ae cancer deaths among white women in the study were from careers of the breast and digestive system, about the same proportion as for ail U.S. white women in 1968. About two-thirds of the deaths for both nonwhite men and women were from diseases of the circulatory system and from cancer. The numbers of deaths for most causes among nonwhites, however, are quite small making interpretation difficult and are presented mainly for completeness. Age-adjusted PMRs for white male and white female emplovees of the 17 PVC fabricators are presented in Table 6 for selected causes of death. There were no similar analyses for nonwhites because for nearly all causes, the numbers of deaths were too small to produce stable PMRs. Expected numbers of deaths have been calculated on the basis of the sex-cause-age specific distribution of deaths among U.S. whites in 1968 applied to the total number of deaths by age among white men or white women in the study group. The midpoint of the study period (1968! was selected for the standard, since it is representative of the study period and provides U-S. mortality data coded according to the eighth revision of the International Classification of Diseases. Ex pected numbers are deaths for individual causes to be expected in the study group if the proportion of tot$l deaths ascribed to a given cause were the same as for the corresponding U.S. race-sex group, while accounting for differences between the age distributions of deaths in the study groups and deaths for the United States. A PMR larger than unity would indicate that the relative proportion of mortality from that particular cause in the study population is higher than would be expected based on the 1968 U.S. mortality experience. Due to the nature of the data, for mal significance tests and interpretation in probabilistic terms are deemed inappropriate. In addition to the numerical value of the PMR itself, the ob served number of deaths is also of interest. The larger the number of deaths observed, the more reliable the PMR. There were two deaths of unknown age among the white males, one a digestive cancer (ICDA 153) and one an unspecified cancer (ICDA 199). These were included in the age groups with the lowest relative frequency for those causes, that is, less than 35 years for total can cer and digestive cancer and 65 and over for other and un specified cancer. Such an assignment has a trivial effect on the ex pectation but is the most conservative way of handling these unknowns, since it serves to increase the expectation (and hence lower the PMR) by the least amount. Based upon both the number of deaths and the value of the PMR, there seems to be an important excess in total cancer mor tality among the white males in the study group. The distribution by specific cancer site suggests that any excess appears to be con- Color. Sox White Mate Female Nonwhite Male Female Unknown Male Female Unknown T Distribution of Deaths Among Employees of 17 PVC Fabricators by Ago, Color, St*.;1964-1973^^;^-^ Alt Afot No. % Under 35 Ho. % 3248 300 601 300 107 24 33 4 180 100 24 300 248 100 38 100 2 100 21 6 20 1 1 11.7 25 0 8.1 2.6 SOO 39-44 No. K 136 42 42 7.0 24 13.3 2 8.3 5 2.0 5 13.2 00 Ac* 45-54 No. * 365 312 100 16.6 28 156 5 20.8 32 12.9 4 10.5 0 0 55-14 No. . % 69 No.-'' 'r% No:" rj 752 23.2 1886.-' --5gj - 123 20.5 312 519---'- -O'-' -i- 1 *i ; - VX 1 a 39 21.7 68 . .V37* ` o.'. . 0 '* 6 25.0 . 5- . 20 8 00 48 .' 8 : 0' 19.4 21'.! ' 07 'i 131 528 12.- A8 -18 ^ 47 4 * ' 2% *5.3* i A SAL 000102691 liver. However, there was a sug'estion that cancers of the lung and brain also appeared with exc ass frequency- The current study, while suggesting an excess in total cancer, particularly digestive cancer, does not clearly point t< marked excesses for cancers of the liver, lung, and brain among vhite men. although the PMRs for these cancers are greater than one. The observed-to-expected PMRs reported by Monson for vjascular lesions affecting the cen tral nervous system, circulatory diseases, and external causes are similar to those reported here. Tabershaw and Caffey, in a ;tudy of workers engaged in the manufacture of v.,ivl chloride ar d its polymers, conclude that no specific cause of death was statistically significantly greater than expectations based upon Stanr ardized Mortality Ratios ISMRs' using the U S. male population ; s the standard a By other criteria, however, the authors conclude there mav be an excess risk for mortality from digestive cance', respiratory cancer, cancer of other and unspecified sites, aru lymphomas. At lower exposure levels, they suggest some exces for cancers of the buccal cavity and cancers of the other and -inspected sites, The current study would seen to indicate that excesses of mor tality from cancer of the digests e system are not sex-specific and are not limited to liver cancer. T ie majority of the PMRs for cancer among both white men and wh te women are in excess of unity, Such results must be interpretec with caution but, since they appear to be consistent with p reviously studied workers, they suggest the need for continue I investigation Summary Results of a study of 4,341 de i ths occurring among current and former employees of 17 PVC fajb ricators during the period 19641973 are presented. The stud was carried out to determine whether any angiosarcoma dt aths had occurred among employees of these fabricators anp to examine the distribution of deaths by cause. No angiosarco na deaths were found among the study population. Distributions by cause of death among white male and white female employi were compared with those for the entire U S . specific for color and sex and adjusted for age bv means of Proportionate Mortality Ratios. There appears to be an important excess in total cancer mortality among both white male and white female employees with digestive cancer, particularly that of the intestine, contributing to the excess. Among the women employees, cancers of the breast and urinary organs may also be in excess. No excesses were found for diseases of the cir culatory system. There were deficits in mortalitv from cirrhosis of the liver among both male and female employees and a deficit in accidents, poisonings, and violence among men. The use of the Proportionate Mortality Ratio based on an external standard requires caution in interpreting these results, but the need for fur ther investigations is indicated. This studv was sponsored bv the following organisations American Can Comnanv B. F Goodrich Companv Diamond Shamrock Corporation. Firestone Tire and Rubber Company lohrs Manville. Motor Vehicle Manufacturers Association Stautler Chemical Company. Union Carbide Corporation. Unirnval. Incorporated References 1. Sehkoff i| and Hammond EC (Eds.): Toxicity of vinyl chloride -- polyvinyl chloride. Ann .V Y. Acad Sci 246:1975. 2. Manual of the international Classification of Diseases Adapted for Use in the United States. Eighth Revision. Washington. D.C., U S. Covt. Printing Office, 1967, Vol. 1. 3. National Center For Health Statistics: Vital Statistics of the United States. 1968 - Volume II - Mortality. Part A. Washington, D.C.. U S. Covt. Printing Office, 1972, pp. 140-205. 4. Chiazze L: Problems of study design and interpretation of industrial mortality experience. lOM 18:169-170, 1976. 5. Redmond CK and Breslin PP: Comparison of methods for assessing oc cupational hazards. lOM 17:313-317, 1975. 6. Monson RR, Peters |M. and Johnson MN: Proportional mortality among vmvl-chlonde workers, tancct 2:397-398, 1974. 7. Lloyd |W and Ciocco A: Long term mortality study of steelworkers: I. Methodology. JOM 11:299-310. 1969. 8. Redmond CK. Ciocco A. Lloyd |W, and Rush HW: Long term mortality study of steelworkers' IV. Mortality from malignant neoplasms among coke oven workers. !OM 14:621-629. 1972. 9. Tabershaw IR and Gaffey WR: Mortality study of workers in the manufacture of vinyl chloride and its polymers. )OM 16:509-518. 1974. Sfiti 00102692 Tibia 4. -- Distribution ol Deaths from Selected Causes Among Employe** of 17 PVC Fabric tors by Sex, White Only, 1964-1973. Cmm of Death tCOA M'Rw. All Causes All Cancers 140-209 Buccal Cavity and Pharynx Digestive System Stomach Intestine Rectum Liver Respiratory System Lung Bone. Connective Tissue. Skin. Breast Breast Genital Organs Urinary Organs Brain & Other Nervous System Other & Unspecified lymphomas Leukemias Diabetes Diseases of the Ciroilatcry System Cerebrovascular Disease Cirrhosis ol Liver Cholelithiasis. Cholecystitis and Cholangitis Accidents, Poisoning, and Viofenca Accidents Suicide All Other Causes fResidual) 140-149 ISO-159 151 ISO 154 155 160-163 162 170-174 174 1B0-187 188-189 191-192 190. 193-199 200-203, 208-205 204-207 250 390-453 430438 571 574-575 ES00-E99B E800-E949 E950-E959 Hal* Fans*la No. 3248 666 % 100.00 20 50 No. 601 181 % 100.00 3012 15 209 41 73 25 6 205 193 24 0 44 36 16 56 42 19 42 1931 289 42 0 46 6.43 1.26 2 25 077 0.18 6.31 5 94 3 53 24 0 12 12 0.50 8.82 1.33 3.99 1.33 0 2.00 2.00 0.74 -- 1.35 in 51 44 19 LI 8.49 732 3 16 183 0.49 172 1.29 0.58 129 18 9 11 0.67 3.00 1.50 617 1.83 59.45 281 46.76 8.90 66 10.98 129 3 0.50 7 022 3 0.50 186 5.79 48 7.99 134 4.13 38 6.32 . 40 123 2 033 372 11.45 74 12.31 Table 5. -- Distribution of Deaths from Selected Causes Among Employees of 17 PVC Fabricators by Sax, Nonwhite Only. 1964-1973. Cause of Death 8th Rov. All Causes All Cancers 140-209 Buccal Cavity and Pharynx 140-149 Digestive System ISO-159 Stomach 151 Intestine Rectum 153 154 Liver 155 Respiratory System 160-163 lung 162 Bone. Connective Tissue. Skin. Breast 170 174 Breast 174 Genital Organs 180-187 Urinary Organs 188-189 Brain & Other Nervous System 191-192 Other & Unspecified 190, 193-199 Lymphomas Leukemias 200-203, 208-209 204-207 Diabetes 250 Oiseases of the Circulatory System 390-468 Cerebrovasarlar Disease 430438 Cirrhosis ol liver 571 Cholelithiasis, Cholecystitis. A Cholangitis Accidents, Poisoning, A Violence 574-575 E800-E999 Accidents Suicide E800-E949 E9SO-E959 All Other Causes (ResiduaQ No. S No. S ISO ICO DO 24 100 00 39 21 66 a 33 33 0 0 00 13 7 ,4 1667 3 1 57 0 0 2 1 11 1 4 16 1 Q 56 Q 0 1 0 56 0 0 7 3 89 0 0 7 3 89 0 0 0 0 3 12 50 0 0 3 1250 4 222 0 0 3 1 67 0 0 1 0.56 0 0 6 3 33 0 0 4 222 0 2 111 1 .4.16 . 2 1.11 0 a*81 4500 8 &U' * 19 1056 3 12.50 3 1.67 1 4.16 -. 0 33 17 2 22 ' 0- 1833 9.44 UL 1232 00 ' , -i 3 12.50 v 1 4.16 0 0--- Y - -------4 16.67 r' centrated in digestive system tancer, given the large number of deaths (31% of all cancer deatHs . For each of the sites within the digestive system, observed nurr bers of deaths are greater than expected. Although, except for in estinal cancer, the observed numbers of deaths are small. The F VIR for liver cancer is rather high, out a definite conclusion is diff : ult with only six observed deaths. On the other hand, the PMR f or cirrhosis of the liver suggests a deficit in mortality from that cause. For white women, the PMR or total cancer appears high, as it did for white men, with can :er of the digestive system and. perhaps, cancer of the breast c i mtributing a fair amount to the ex cess. The PMRs for individual s tes within the digestive system are based upon small numbers be t suggest an increase in intestinal cancer. The PMR for urinary c ncer. though based upon only 11 deaths, seems strikingly high ar d may be an indication for further investigation. On the other han d, in contrast to the observation in white men. the PMR for respira ory cancer among white women Is very close to unity. Similar to tie observation in white men, mor* tality from cirrhosis of the liver seems to be in deficit, but the corresponding observed number of deaths is quite small. Among both white male and female employees, diseases of the circulatory system account for a large percentage of total deaths. In each case, observed numbers of deaths are close to expected. There appears to be a somewhat different pattern among men and women for deaths due to accidents, poisonings, violence with the number of deaths somewhat low among men and high among women. There were 39 cancer deaths among nonwhite men. somewhat greater than expectation, although the numbers by site are too small for meaningful analysis. Mortality from cerebrovascular disease appeared high (PMR = 2.11) but the finding was based upon only 19 deaths. Discussion The present study was designed with two objectives. The first was to determine whether or not any angiosarcoma deaths had SAL 000102693 TiW 6. -- Observed and Expected Deaths for Selected Causes Among Employees of 17 PVC Fabricators by Sex, White Only, 1964-1973. ClUW 9< Outtl All Cancers Buccal Cavity and Pharynx Digestive System Stomach Intestine Rectum Liver Respiratory System Lung Bone. Connective Tissue. SXtn. Brea t Breast Genital Organs Urinary Organs Brain & Other Nervous System Other & Unspecih 1 Lymphomas Leukemias Diabetes Diseases o( the Circulatory System Cerebrovascular Disease Cirrhosis ol Lver Cholelithiasis, Cholecystitis, and Cholangitis Accidents. Poisoni i8. and Violence Accidents Suicide 8th Rev. 140-209 140-149 ISO-159 151 153 154 15S 160-163 162 170-174 174 180-187 188-139 191-192 190. 193 199 200-203, 208209 204 207 250 390 458 430-438 571 574-575 E800-E999 E8006949 E950-E959 Observed 666 15 209 41 73 25 6 205 193 24 0 44 36 16 56 42 19 42 1931 289 42 7 188 134 40 Expected 561.997 16.875 162.143 31.507 52.528 19.631 4.190 176.657 165.566 15.117 -- 52.828 33.131 13 885 34.607 32.382 23.364 49600 1832.515 292 074 62.821 6.349 265.548 189.268 52.325 PMR* 1.19 0.89 1.29 1 30 1 39 1.27 1.43 1.16 1.17 1.59 -- 0.83 1.09 1.15 162 1.30 0 81 0.35 1.05 0.99 0.67 1.10 0.71 0.71 0.76 Observed iai 3 53 8 24 8 0 12 12 51 44 19 n 4 18 9 1 11 281 66 3 3 48 38 2 Expected 137 699 1 896 35.342 4.981 15 344 3.877 0.633 11.888 11.224 35 661 32.397 23.297 4.537 3.499 9622 7.631 5.005 15.436 309.232 71.965 12.343 1.7B3 40855 27.931 ,9.171- , PMfl* 1.31 1.58 1 50 , 61 l 56 2.06 _ 1.00 107 1.43 1.36 0.82 2.42 1.14 I.B7 1.18 0.20 0J1 oil 092 0.24 168 1.17 1.36 0.22 ' PMR is the ratio of observed (o expected where the exacted number is calculated on the basis of the distribution of deaths Ay the total U S. in 1958 specific for color, sex, cause, and age. occurred among en ployees of the PVC fabricators under study. Since no arigiosarco na deaths were found among the employees studied, the first que ition has an unequivocal answer. A secondary objective was that of examining the distribution of deaths by cause among the err ployees under study. Implicit in that objective is the question of vhether or not that distribution is, in some sense, unusual. Tht re is no unequivocal answer to the latter question. Whether >r not an observed distribution of causes of death is unusual clparly relates to the standard or comparison population as well as the analytic methodology.4 On the basis of a proportionate mortality analysis, there appear to be excesses in t >tal cancer mortality among both white men and white womei in the study, when compared to the distributions of deat is for the total United States specific for color and sex and adjusted for age. Excesses in cancer mortality appear concentrated in car cers of the digestive system and, in particular, in cancers of the in estine for both men and women. In addition, there is a suggestioi that mortality from cancer of the breast and urinary organs amor g white women employees is higher than that for the total U.S. There are, however, several reasons why definitive interpretation is difficult. It has, for example, been suggested that a Proportionate Mortality Ratio based on an exter nal population may not be sufficiently discriminating in screening for potential hazards.5 In addition, an analysis using PMRs fails to take account of the absolute risk of dying in the population under study.6 Further, a number of studies have suggested an overall favorable mortality for industrial working populations, even in those where well-defined hazards increase risk for a specific cause.7 8 Factors such as these are meant to suggest that proportionate mortality analysis must be interpreted cautiously, with the intention of providing leads for further investigation. Results consistent with those of previously published studies would be of particular interest. With no comparable working populations in the fabrication industry, potential contrasts may be found in studies of vinyl chloride workers. Monson, et al, provided a proportionate mortality analysis of 161 deceased workers (all presumably white males) in two plants, one where vinyl chloride monomer is produced and one where it is polymerized into polyvinyl chloride.6 Results of that study suggest a possible excess in total cancer mortality, primarily cancer of the SQL 00o 694 f,W ^?v/C Polyvinyl Chloride Pneumoconiosis: Epidemiological Study of Exposed Workers Giuseppe Mastrangeipj, M.D.; Maurizio Manno, M.D.; Guido Marcer, M.D,; Giovanni Battista Ba tolucci, M.D.; Carla Gemignani, M.D.; Giulia Saladino, M.D. Lorenzo Simonato, h D.; and Bruno Saia, M.D. /Among 7276 work vs who were employed in a polyvinyl chloride production actory and who had had no previous dust exposure e/sev here, 20 cases of pneumoconiosis were found. Chest x ay abnormalities were characterized by limited profusion, irregular type and low gravity. All 20 workers had been e posed to high PVC dust levels. The chest x-ray changes were observed after a minimum exposure of five years and, in a small percentage of cases, ;were associated witf slight restrictive respiratory function impairments. Moreo\ er, in the whole group of workers 398 'cases (31.9%) were ound with non-specific x-ray abnormalities mainly relattd to age and smoking. Polyvinyl chloric e (PVCi dust is particularly relevant to a consideration of the anatomical, clinical and radiological signs of pneumoconiosis found in workers exposed to "inert" dus s because of the high annual production of PVC and the number oi exposed workers Within the tram e work oi a national survey on vinyl chloride hazards o humans, coordinated by the Chemical Workers Unions, the authors examined the working population of plants producing PVC in Porto Marghera. Italy One group of workers was exposed to PVC dust, another g oup worked in department* polluted onl\ bv vinyl chlori e monomer (VCM) The characters? cs and prevalence ot pulmonan. radiological abnorn alities found are reported and their pathogenic mechan sm is discussed in this article Methods and Popul >tion l nvironmental dt. st sampies were collected and both c onceniration in air and particle size were measured In mu o' Padova. Padova luK 5-G the drying sacking and blending departments. PVC dus; concentrations were higher than the TLV {10 mg nt o' total dust) m about 60% of the sample* In the polvmenzation departments, no concentration higher than the TLV w'as found. In the samples taken, pariici'-' with diameters of 1 pm to 5 fim constituted A b% to 30.9% of total dust weight All the workers answered the European Coal and Steel Community (ECSC) questionnaire tor chronic hronrniie and emphysema,' and were submitted to chest \-ra\ tn; cording to ILO standards) and spirographic exammapo: (Godart-E xpirograph Bilthoven. Holland) Chet.: t-u\ films were read bv two independent physician* utili/m^ the ILO/UC Pneumoconiosis Classification 19?: - f statistical analvsis a consensus reading a> uo-*d U each worker examined, present and past working hwto'^'- were carefully recorded and particular consideration w .e given to previous dust exposure Of the total. 1.21^ M>h tects had had no past exposure to organic or inorg.uv dusts. 731 had been exposed to PVC dust (employed drying, sacking and blending of polymer), and nan been exposed to monomer alone Results Table 1 shows the mean and standard deviation o' ag* and ot length of exposure, the number of sublets and tt> percentage of smokers in the two groups, those exj>o<*3 to PVC dust and those not exposed There are no sij.nvcant differences n age and smoking habits, but the c../.' tion ot exposure is higher in the workers not e\r*c>v`" t> dust. In 20 subjects (1.6%). we diagnosed a pneumoconiosis. ie. chest x-ray change' (irruk-.i**' opacities or f rankly rmcronodular images) ot at lea>t i 1 profusion according to the ILO'UC cla>sitcatK>n It** 00010 Table 1. -- Age, Exposure, Number of Subjects and Percentage of Smokers in PVC Dust Exposed and Nan-Exposed Groups Age (Years) Mean S.D. t Exposure (Years) Mean S.D. No. o! Subjects % of Smokers l PVC dus: exposed group PVC oust non-exposed group 37.7 8 8 6 1 35.7 8 5 8 6 < 0 731 73.9 < 5 485 68 7 i 11 i mean age of this groL 3 was 44.9 { 5.2) years and the ing x-ray abnormalities -- since the interaction is not mean length of expost re was 11.6 ( 5.4) years, 16 sub significant, the effects are simply additive. jects (80%) were eithe smokers or ex-smokers, The square of a multiple-partial association coefficient Table 2 summarizes he distribution of cases in relation tor qualitative data was calculated to measure the degree i to age and length of ex] iosure In all age groups there is an increase of disease pre 'alence associated with increasing of association between the dependent variable (x-rav changes) and each of the two predictor variables (age and i i length of exposure In the case of x-ray changes. 16 subjects had class 1/0 p r^fusion; two cases, class 1/1; one exposure).' Age and exposure are alternately held cons tant. Age is a most important factor When exposure is ;t case, class 2/1; and one case, ciass 2/2 In spite of age and held constant, 33.2% of the x-ray changes are shown to the considerable expos jre, the majority of cases observed depend upon age; when age is held constant, 6.5% are were in a low profus category, thus indicating a slow shown to depend upon exposure evolution of the dtseast The changes were characterized Table 5 summarizes the distribution of cases (same by irregular opacities ten cases were type "s"; three subjects as Table 3) according to smoking habits in cases, type "t"; six casejs, type "p"; and one case, type "r." The opacities were di fused, mainly over median lobe workers exposed and not exposed to PVC dust. In Table 6, the two-way analysis of variance for proportions shows 11 areas Two subjects s wed slight restrictive spirographic that both risk indicators have a significant influence on impairment All had \ ad jobs vvhich involved high air chest abnormalities borne dust levels (mos ly drying and sacking) for at least There is no interaction of factors Habitual smoking five years None of th( 20 subjects was in a group unex- plays a major role and. when exposure is held constant, is posed to dust None c t them had experienced previous shown to be responsible for 17.1 % of the changes When occupational exposure to organic or inorganic dusts We smoking habits are held constant, exposure to PVC dust is considered the above alterations to be PVC pneumo- shown to be responsible for 6 9% of the x-ray abnor coniosis malities In 388 subjects (31 9%) we found slight chest x-ray alterations consisting of linear or irregular vanishing Discussion opacities, or both, clas ified as class 0/1 profusion; the re X-ray changes of at least class 1 profusion, found in 20 maining 808 subjects vere class 0/0. subjects, are considered PVC-induced pneumoconiosis Table 3 reports the total population distribution, ex- This claim is based on the following (1) Reading of the eluding 20 subjects w it 1 PVC pneumoconiosis. Results are chest films was performed by two independent physi presented in a two-way table -- each entry reports the cians, who were not informed of the age, job, length of ex number of observation^ Samples are classified according posure or clinical history of workers A consensus reading to age (three classes) and polyvinyl chloride dust ex- was required for the pneumoconiosis diagnosis (2) posure. "PVC +" represents presence and "PVC Special attention was given to the absence of an\ absence In the table,' -ray + " indicates the classes with class 0/1 profusion To assess the influence of both risk indicators we performed a two-way analysis of variance for previous occupational exposure to organic or inorganic dusts. (3) The changes were found in workers who had ex perienced prolonged exposure in departments with \l ut proportions (Snedecor and Cochran)J The column mean is adjusted for row etf< cts and vice versa We also tested whether row and colu n effects were additive or whether demonstrated PVC dust pollution The length of exposure was about 12 years on the average and never less than five No radiographic signs ot pneumoconiosis were i i interaction was preseHt . The results (Table 4) show that both age and exposure were significant factors influenc found in subjects working in departments free of PVC dust, although the average period ot exposure was longer i I I Table 2, -- Distt bution of PVC Pneumoconiosis in Age and Exposure Classes {The percents e on the group of same age and exposurt is shown in parentheses). PVC Dust Exposure (Years) <5 5-10 >10 < 3D - Age (Years) 31-40 41-50 2(2 4) 2 (3 8i 5(8.3) 8(9.0) >50 1(5.9) 2(9.5) Table 3. -- Distribution of Cases wrth Class 0/1 and 0/0 Prolusion According to Age and PVC Dust Exposure. PVC 4 X-ray + X-ray - PVC X-ray + X-ray - < 30 20 133 17 119 Age (Years) 31-40 41-50 76 123 19' 106 4;- 56 155 67 > 50 35 17 15 c Journal of Occupational Medicine/Vol. 21, No. 8/Augus! 1979 541 SAL 000102696 * Jble 4. -- Two-Way Analysis jof Variance for Proportions {Same cases as in Table 3). Source ol Variation Age PVC dusl exposure infraction Error Degrees of Freedom 3 1 3 1186 Sum ol Squares 30 97t3 0 7643 0 93S2 227 9403 Mean Squares 10 3236 0 7843 0.3294 0 1919 F 53.8V 4 09| 1.72 *p < 0.01 tP < 0.05 Table 5. -- Distributio i of Cases with Class 0/1 and 0/0 Profusion According tc Smoking and PVC Dust Exposure. PVC + X-ray + X-ray PVC X-ray + X-ray Nonsmokers 40 147 25 127 Smokers 216 308 107 226 in these workers (Tabl k n Previous experimen al data on animals and reports of human lung biopsy indicated the possibility that the im pairments described a >ove can be attributed to PVC dust inhalation In 1970 zende et als reported a case of pneumoconiosis in a Worker exposed to PVC dust Chest x-ray films showed srr all patches which became denser toward the hilum Bic psv revealed multiple granuloma tous centers consisting of foreign amorphous material sur rounded by granulation tissue composed of histiocytes, lymphocytes, plasma :ells, eosinophils and foreign body giant cells Such centers were associated with moderate diffuse fibrosis. A histiocytic-macrcfphage reaction in alveolar septa. observed by Frongia e: aP in guinea pigs exposed to PVC dust in a sacking depa tment. developed into lesions with multiple granulomatc us centers with giant cells during the course of exposure . Rats exposed to a similar working environment develo >ed marked thickening of in teralveolar septa with|an evolution similar to that in the guinea pigs Such experimenta and pathologic data confirm the results of this epiderr iological study Lung changes are directly related to PV C dust while VCM exposure alone fails to cause these cf anges Therefore, unlike Lilis el al we believe that pulmc nary changes are not pathogemcalv similar to other vinyl chloride induced abnormalities (fibrosis of the live . scleroderma-like skm changes, peripheral vascular d mage) In the present stud there was only a 1 6% prevalence of pneumoconiosis in a lota) population of 1,216 subjects Nevertheless in workers exposed to effective risk of pneumoconiosis (731 subjects) the prevalence rose to 2 7% Waxweiler el 2P reported pulmonary' fibrotic changes associated with respiratory function impairments in % subiects exposed to PVC dust. Lilis et aP studied the chesi x-ray films and changes in respiratory function of groups of PVC production workers who had experienced exposure of different degree and length. They found a 4.3% to 22.7% prevalence of chest x-ray changes {small, linear, reticular and/or rounded opacities) and spirographic impairments related to the duration of exposure and to the presence of chest x-ray changes. As these authors did not employ either the ILO/UC International Classification or any other, no comparison concerning the reported prevalence can be made with the present data Apart from 20 cases of pneumoconiosis, mild non specific alterations (.profusion of 01 class) were found both in the group exposed to PVC dust and in the group exposed to VCM alone Such changes are related mainly to age and smoking habits, and the role of exposure is minor References 1 Commission or the I urop-'an Communities Notes on the 19n i CSC Queshonnruif tm Stud'my Chrome Bronchitis and .Pulmonarn i-mnhv-t'mfl. 1972 A Mmotio, D Bnlle. R van dm Lendc f Sann.H R.mriarcio. .ind U Smidt It-ds] Industrial Hygiene- and Medicine lest' No 1 4 On k i` tor Oi i k ial Public at ions oi the t uroix'an C om- mum I it's. 1. uvpnibtuirj: 197.1 2 Jacobson C. and Lainhan WS IIO'UC 1971 International classification o' radiographs ol the pneumoconioses Med Rad'Of Photop' 4S 67. 1972 3 Snedecoi C.V\ and Cochran WC Statistical Method' Sixth id' t icin Ames the loss a Stale Umversils Press. liyhlh Printing 197t< pp 472-SOl 4 Blalock HM Social Statistic' Second Edmon Ness lev! McCrass Hill Book Company 1972. up 4StMS9 5 S/ende B. lapis h. Nemos a and Pmtc-r A Pneumocomo-rcausod by the inhalation o! |>oh s-ins I chloride du't Met? ia. 61 433-436. 1970 fa Wongiri N Spina//ola A and Bucarelli A Lesioni pntmona' sperimenuli da mala/1 mn* pmlunpata di tioiven di PVC m amhientf ct' lavoro Medias 6S 321-342 l'i74 7 lilts R. Anderson H. .Miller A andSelikoitll PulmonarvihanL--among vinyl r hloudr poh-men/atron vs or kers Chesf 69 2'+J-103 1Q fa Waxsveilfi R| Sinn^-t W. I all. H et al NIOSH Neoplfl'tic nU. aniony vrnyl f hloudi- pol\ mi'tir.tlion " orkers. 1-1 fa 3nn.M AcaoSc271 40-48. 197u Table 6. -- Two-Way Analysis ot Variance tor Proportions (Same cases as in Table 5). Source of Variation Smonnc PVC cusi exposure ntera:iion E rro: Degrees of Freedom : 1192 Sum ot Squares 7 east i 76-7 0 1023 2M 9125 Mean Squares 7 8850 1.7847 0 1023 0 211? ------------------------------ 1 i F 37 31 ' 44' <1 I 1 1 1 1 *6 < 0 01 54? Polyvinyl Chloride Pneumocomosis/Masirangelo ei a SAL. 000102697