Document w3Ywe6YLkOzrypbqJgXRKop4

Breast Cancer Mortality Among PVC Fabricators Leonard Chiazze, Jr., Sc.D.; Otto Wong, Sc.D.; William E. Nichols, Ph.D.; and Lorraine D. Ference, M.S. A case-control analysis of breast cancer deaths among PVC fabricators is presented. This study is an extension of a cross-sectional mortality study of deaths occurring among 17 PVC fabricators during the years 1964 to 1973. Relative risk estimates were derived and tested usjng the MantelHaenszel procedure Although no statistically significant relative risks were found, a least significant relative risk analysis indicated that the underlying relative risk would have to be on the order of three to one ip order to be detected. There does seem to be reasonable assurance that very large increases in risk for breast cancer do not exist among these PVC fabricators. The authors have previously reported the results of a cross-sectional mortality study of deaths occurring among current and former employees of 17 PVC "fabricators during the years 1964 to 1973.' That study identified 44 deaths among white women for which the underlying cause of death was cancer of the breast Those 44 deaths attributed to cancer of the breast occurred among employees of eight of the 17 participating.com panies. On the basis of a proportionate mortality ratio (PMR) analysis, the observed number of deaths from breast cancer was found to exceed the number expected based upon the distribution of deaths by cause and age among all U S. white women in 1968. The original mortali ty study focused on deceased employees who worked anywhere in the study plants where PVC fabrication was carried on. A decision was reached to investigate further by carrying out a case-control study which would attempt to determine whether either the cases or controls could have been exposed to PVC during their employment and to estimate the relative risk for breast cancer among those exposed to PVC and those not exposed. Materials and Methods Controls were to be selected from among deaths from diseases of the circulatory system (ICDA 390-458, Eighth Revision) and accidents (ICDA E800-E999) since no in creased mortality was found for these conditions. An at tempt was made to match cases and controls by com pany (plant if possible) and age plus or minus five years. Thirty-five of the cases could be matched on both criteria. There were nine breast cancer deaths which could not be matched both on company and age. Con trols for these cases were drawn at random from the pool of potential controls with matching on age alone in order that every breast cancer death have at least one matching control. The basis for this report is a total of 44 breast cancer deaths (cases) and 134 controls matched for age and distributed among five companies. In planning the fieldwork, emphasis was placed on ob taining employment histories on the cases and matched controls. A variety of jobs were held by both cases and controls, ranging from office and clerical work to produc tion jobs such as bench inspector, press operator, trim mer, assembler and sweeper. The wide range of job con tent and location made it impossible to determine precisely whether there was PVC exposure in every case or the precise length of that exposure. Therefore, a sub jective ranking system was developed to classify expo sures. Work histories were reviewed with knowledgeable plant personnel, and PVC exposure potential was cate gorized into five classes -- no exposure, improbable ex posure, possible exposure, definite exposure, and unknown exposure. The various categories of exposure potential through employment, and examples of each, are as follows: Classification of Exposure Potential Examples From the Division of Biostatistics and Epidemiology. Georgetown University School of Medicine, Washington. DC 20007 (Dr. Chiazze and Ms Ference), Tabershaw Occupational Medicine Associates (Dr. Wong), and International Harvester Company (Dr. Nichols, formerly with Organization Resources Counselors. Inc ). No exposure Employment terminated before PVC use PVC processed in a separate building from decedent's work station Journal of Occupational Medicine/Vol. 22, No. 10/0ctober 1980 677 BFG38848 Improbable Possible Definite Unknown PVC processed in the same building but removed from decedent's work station Decedent handled only fabricated products Work station in vicinity of PVC resins; periods of no monitoring or with no detectable level of VCM Direct work with PVC resins. Moni toring indicated a detectable level of VCM Employment records not complete enough to determine potential for exposure Results A total of 44 breast cancer deaths and 134 controls matched for age and distributed among five companies was available for analysis. Comparison of cases and con trols on a variety of variables where information was available, including length of employment with the com pany, continuous vs. intermittent employment ever mar ried vs. never married, and child-bearing history, reveals no statistically significant differences (p > 0.05) between cases and controls for any of these variables. The distribution of cases and controls by exposure category is given in Table 1. This classification scheme enabled some definitive exposure statement in 80% of the cases and 92% of the controls. After matching by age and company, 38 matched sets of cases and controls were developed from the 44 cases and 134 controls. There are fewer matched sets than cases because, in six instances, it was necessary to com bine cases of similar age within the same set in order to have at least one control per matched set The MantelHaenszel procedure was used to derive a summary estimate of relative risk and to test for significant depar tures from unity.11 In this procedure, each of the 38 sets can be viewed as a 2 x 2 contingency table. Thus the i* set can be represented as follows: ' Cases Controls Total PVC Exposure Yes No Total A, B, N,, C, D, N2j M,' Mjj T, Relative risk is defined as the ratio of the probability of dying from cancer of the breast among women exposed to PVC to the probability for women not exposed. Estimates of these individual probabilities are not avail able from a case-control study. However, a measure of estimated relative risk from case control studies as sug gested by Mantel and Haenszel has been calculated as: I A,P, R = 1. T' _ K I B,C, T, To assess whether the departure from unity of an ob served relative risk is too great to have occurred by chance alone, a summary chi-square test corrected for continuity was performed using the Mantel-Haenszel pro cedure. The calculated chi-square must be 3.84 or larger in order to conclude with 95% assurance that the ob served relative risk did not differ from unity by chance alone. Combining the five exposure categories into two may be accomplished in a variety of ways resulting in several possible relative risk measures. For example: 1. Yes = Definite exposure only No = No exposure only (Ignore improbable, possible, unknown) R = 1.81 xA',TM = 0.0189 (not significant) 2. Yes = Definite + improbable + possible + unknown No = No R = 1-94 X,mh=1119 (not significant) 3. Yes = Definite + possible No = No + improbable (Ignore unknowns) R = 0.624 xjmh = 0.0194 (not significant) 4. Yes = Definite + possible + unknown No = No + improbable R = 2.73 Xjmh = 1-548 (not significant) None of the above calculated relative risks, including number 2, which treats anything other than no exposure as definitely exposed, are statistically significant; i.e., they may have occurred by chance alone. Similar analyses were carried out on a company-by-company basis. None of the relative risks so calculated is significantly different from unity. Conclusions The results presented here must be interpreted with caution. Absence of a statistically significant relative risk does not demonstrate that there is not an excess risk of death from breast cancer among white women employ ees with PVC exposure. In fact, when no statistically significant relative risks are found, it is pertinent to ask what the chances are of detecting an increase of a given magnitude from the available data. Using the method described by Walter,4 the authors have subjected each of Table 1. -- Distribution of 44 Breast Cancer Deaths and 134 Matched Controls by Exposure Category. Exposurt Category No exposure Improbable exposure Possible exposure Definite exposure Unknown exposure Total Casts NO. % 27 61.4 6 13.6 00 2 4.5 9 20.5 44 100 Cases No. % 97 72.4 17 12.6 4 3.0 6 4.5 10 7.5 134 100 678 Breast Cancer Mortality Among PCV Fabricators/Chiazze et al BFG38849 the relative risk estimates to a least significant relative risk analysis under the conditions that they desired 95% assurance that a risk of such magnitude, if observed, did not occur by chance alone and 80% probability of detecting the least significant relative risk if it exists. Results of that analysis are as follows: 1. Definite exposure only vs. no exposure only Relative risk estimate = 1.81 Least significant relative risk = 6.77 2. Definite -4- improbable + possible + unknown vs. no exposure Relative risk estimate = 1.94 Least significant relative risk = 2.92 3. Definite + possible vs. no exposure + improbable Relative risk estimate = 0.624 Least significant relative risk = 5.02 4. Definite + possible + unknown vs. no exposure + improbable Relative risk estimate = 2.73 Least significant relative risk = 3.41 Even in case number 2, where all but "no exposure" are counted as exposed, the smallest relative risk which could be detected from these data is nearly 3:1. In this instance. over 130 cases and 130 controls would have been necessary to detect a true doubling of the risk under the specified conditions. In order to achieve 95% probability of detecting a true two-fold risk, if it in fact existed, well over 200 cases and 200 controls would have been re quired. Given the sample size in this study and the percentage of controls exposed (a percentage which was unknown at the start of the study), it would be possible to detect only very large increases in risk. There seems reasonable assurance, therefore, that such very large in creases in the risk for breast cancer do not exist among these PVC fabricators. References 1. Chiazze L, Nichols WE, and Wong O: Mortality among employ ees of PVC fabricators. I Occup Med 19:623-628,1977 2. Mantel N and Haenszel W: Statistical aspects of the analysis of data from retrospective studies of diseases. / Nat/ Cancer Inst 22:719-748, 1959. 3. Pike MD and Morrow RH: Statistical analysis of patient-control studies in epidemiology: Factor under investigation an all-or-none variable. Br I Prev Soc Med 24:42-44, 1970. 4. Walter SO: Determination of significant relative risks and op timal sampling procedures in prospective and retrospective com parative studies of various sizes. Am ) Epidemiol 105:387-397,1977. Light in Darkness I am not tragic or desponding by nature. Temperamentally I am buoyant and hope ful. Through the darkness I always see a light -- a bright star that no misfortune ever quite hides from me. . . With an embossed book on my knee, or seated at my typewriter, I am not conscious of any handicap. In spirit and mind I am untrammelled. Imagination rides Olympian horses. Once my foot is in the stirrgp, I am off to the uttermost isles of thought I ought to say also that I have received the most wonderful kindness from my fellow creatures. Everyone has given'me of his best in proportion to the richness of his nature and the goodness of his heart -- Helen Keller, as quoted in Helen and Teacher by loseph P. Lash. Published by DelacoAe Press, New York. N.Y. lA i^ C'J ca o o l Journal of Occupational Medicine/Vol. 22, No. 10/0ctober 1980 bFG38850 679 > hum,in Nit >.il t la*^ m ^ nr >//( nit' inset lu uf(' 3*'/ I \ird * pi'Mii ido ' iron Hhh robl('m> or ' 2:80-85. biphonvl Prt'sia idr ' levels m Pf'^nndr postic idev in and en hances Ef- 1 assman Mortality Among Employees of PVC Fabricators Leonard Chiazze, Jr., Sc.D.; William E. Nichols, Ph.D.; and Otto Wong, Sc.D. A cross-seetional mortality study of 4,341 deaths occurring among current and former employees of 17 PVC fabricators during 1964-1973 is presented. The objectives are: (1) to iden tify any angiosarcoma deaths among the employees of these fabricators, and (2) to examine the distribution of deaths by cause. No angiosarcoma deaths were found among the study group. Sex-race-cause-specific Proportionate Mortality Ratios (PMR's) were computed, using the corresponding U.S. mor tality as the standard. Among white employees, there appears to be an excess in total cancer 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 both male and female white em ployees. The lanuary 1974 disclosure of three deaths from angio sarcoma of the liver in a single vinyl chloride polymerization plant and the attention focused on this new occupational disease are well known. A significant amount of information from animal ex perimentation and observation on humans engaged in the produc tion of vinyl chloride followed.1 However, there was no informa tion regarding the possible adverse effects on employees engaged in polyvinyl chloride (PVC) fabrication, where potential exposures were thought to be low and to result from the release of unreact ed monomer trapped in the resin. This issue was considered of great import because of the very large number of workers believed to be engaged in fabrication. In March 1974, representatives of PVC producers, who are members of the Organization Resources Counselors (ORCI, Oc cupational Safety and Health Standards Croup, contacted ORC about the feasibility of a study of health risks to employees work ing with vinyl chloride and polyvinyl chloride. Since the National Institute for Occupational Safety and Health (NIOSH) was con ducting a study of vinyl chloride and resin producing employees, the scope of the proposed ORC study was limited to employees of From the Division of Biostatistics and Epidemiology. Department of Community Medicine and International Health, Georgetown University School of Medicine. Washington. DC 20007 (Os. Chiazze and Wong) and Organization Resouces Coun selors, Inc., Washington. DC 20006 (Dr. Nichols). 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 ujoon 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 C, ) Journal of Occupational Medicine/Vol. 19, No. 9/September 1977 623 \ --vC BFG38851 (i.e., past ten years) decedents. The desirability of identifying an historical cohort for follow-up was recognized, but it was deter mined that it would not be possible to identify clearly and com pletely the necessary cohort of workers within a reasonable period of time, if at all. As a consequence, this study is based upon 4,341 deaths which occurred during the period 1964-1973 among current or former employees of 17 companies engaged in PVC fabrication. A total of 55 plants supplied data on all identifiable deaths since, as was mentioned earlier, it was not possible to iden tify those employees with only vinyl chloride exposure for the study In order to be included in this study, a deceased employee fell into one of the following categories: (1) employee died while ac tively employed, (2) employee died after retiring from the com pany with retirement benefits, and (3) employee died after ter minating employment but with vesting in a company-sponsored life insurance plan. Deaths occurring among former employees with less than the number of years necessary for insurance vesting were not included in plant records and were, therefore, not available for this study. An attempt was made to compensate for at least some of the "leakage" due to employees leaving the industry prior to the time they were vested in any insurance program by using the following procedures. Once death records for a given company were iden tified, death certificates were obtained and separated into two groups as follows: (1) all deaths with cancer (ICDA 140-205 up to 1967; ICDA 140-209 for 1968 on), or liver disease (ICDA 580-586 up to 1967; ICDA 570-576 for 1968 on), or suspected liver con dition mentioned on the death certificate; and (2) all deaths from causes other than cancer or liver disease. Death records men tioning cancer or liver disease and giving a hospital as place of death were segregated and sorted by hospital. Where there were several death records for a single hospital or several hospitals in the same area, arrangements were made for a Registered Records Administrator (RRA) to visit the hospitals, review medical records, contact the hospital pathologist and review pathology records to determine whether there were any angiosarcoma cases in the hospital's pathology records. If so, an attempt was made to deter mine whether or not the angiosarcoma possibly could be related to vinyl chloride exposure. This procedure enabled us to identify whether any employees, 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 from angiosarcoma of the liver; according to company employment records, none were employed at any time in PVC fabricating plants. These deaths were reported to OSHA. NIOSH, and CDC for inclusion in the nationwide angiosarcoma survey. Death certificates not 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 hospitalization of the decedent and whether there was any indication that he or she had cancer or liver disease. Additionally identified hospitals were contacted as above. Originally, it was planned that death certificates would be ob tained from life insurance carriers. In practice, both company and life insurance records were used because of record retention prac tices and retrieval problems in the insurance carriers. All available death certificates were 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 in 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 (one 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 (PMR) 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 (e.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. TaMt 1. -- Dtetribott* *! D*ath* Among Employ** *1 17 PVC Fabricators fey Tsar el Death. 1964-1973. Ymt DmMi 1964 1965 1966 1967 1966 1969 1970 1971 - 1977. --1973- iMii N*. 32$ 345 400 429 499 449 m.- . : ;..>471;..V--: .sv. .,. % 75 60 93 90 115 10J 10.7109 IT*.,. r. Tv H cr. <- o 0J -V >yC' 624 Mortality Among Employees of PVC Fabricators/Chiazze, Nichols, and Wong BFG38852 of the In- found to a plant - '0 in e in le out of changes industry t ranged jyees) to ployees). and 500. isely, it is le end of mortality r, results ios (PMR) 'MR uses i a comths from propriate vould be lar group ed to the was not d States, ' Despite i unusual nnot be oyees of rrease in decade nployee er years t four of owever, :ords for thereby Tab)* 2. -- Dhtribotlon af Daath* Amon( Employ*** of 17 PVC Fabricator* by Color and Soi, 1964-1973. Rm Total Whitt Nonwhitt Unknown Sox Total Mad Formlo Unknown 4341 3676 663 2 3849 3241 204 180 601 24 0 0 288 248 38 2 The distribution of deaths in the study group by race and sex is given in Table 2. Most deaths (84.7%) occurred among males. The vast majority (88.7%) of decedents were white and there were 288 (6.6%) for whom race could not be determined. Table 3 shows this distribution of deaths by age. For both white male and white female employees, more than half of the deaths occurred among those aged 65 and over (58.1% and 51.9% for white men and white women, respectively). The corresponding proportions of deaths which" occurred after age 65 in the (Jnited States population in 1968 were 59% and 72%, respectively). The higher proportion of deaths among white women over 65 in the U.S. population compared to the employee population may indicate that relatively fewer women work to retirement age than do men. While the numbers of deaths among nonwhite employees are too small for any definite conclusions, the distribution of deaths by age among nonwhite men is roughly comparable to that for the total United States. Tables 4 and 5 show the distribution of deaths for selected causes by sex for whites 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 1ICDA 140-209). The corresponding percentages for the total U.S. population of white males in 1968 (midpoint of the study period) > were 54% for diseases of the circulatory system and 16% for can cer. Digestive and respiratory cancers account for somewhat less than two-thirds of all cancer deaths among the white males in the study group as compared to about 59% of all cancer deaths , among U.S. white males in 1968. For white women, over 46% of the deaths are from diseases of the circulatory system (compared to 57% for all U.S. white women in 1968), and 30% were from can cer (compared to 18% for all U.S. white women in 1968). Somewhat over half of the cancer deaths among white women in the study were from cancers of the breast and digestive system. about the same proportion as for all 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 employees 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 total 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, Sax hmm Mad Farad v-.-`v:sarnR.; TaMt 3. -- OMribwtle* of Duths Amonf Employ*** ol 17 PVC Fabricator* by Aft. Color. $ox,19df-1973. A8 Afa do. % IMor 35 No. % 3248 100 601 100 107 24 33 40 3544 It*. % IK 4 2 42 7 0 45-54 N*. * MS 112 100 188 55-44 * % 752 232 123 205 > Wii rarr; do. . v -lW v- 581, Sli ; (Mam d*. 2 01 00 - nd Wong Journal of Occupational Medicine/Vol. 19, No. 9/September 1977 BpG38853 625 Tab)* 4. -- Distribution ol Daatlu Irani Salactad Crums Aiuoar Employt*< si 17 PVC Fabricators by Sa>, Whit* Only, 1964-1373. Cana at Death All Cnnn All Cancers icon till Hay. 140 209 Malt 3Z48 10000 SOI 10000 666 20.50 181 3012 Buccal Cavity and Pharynx 140-149 046 0.50 Digests System 150-159 209 6.43 882 Stomach 151 126 1.33 Intestine 153 225 3.99 Rectum 154 25 0-77 133 Liver Respntory System 155 160-163 0.14 205 631 2.00 Luna 162 193 5.94 2.00 Bone, Connective #fisa*e.-SMa. Breast^- lJM7fc^-. *35? 174? i- 6enital-ftpn:.,-^ji-r! UMO 24 -o w.ii,-y -.44':-^-- I3^V59 - iUrieuy j-lttry `iiima Syttmi - 1R6-189 `-P- *f.V*gy . 191-132 36 ' 16 1-11 11 . litis V*~ -h - 049 - ,Uv^ #J67;?| ^ puw, 4 Unspadfiad , 190, '193-199 Table 5. -- Distribution ef Daatha (rent Seltnted Case Employees ol 17 PVC Fabricators by Sex, Nonerbllt Only, 1964-1973. Causa ol Death All Causes All Cancers 8uaal Canty and Pharynx Diyestivt System Stomach Intestine Rectum liver Respiratory System icon 8th Rae. 140-209 140-149 150-159 151 153 154 155. 180 100.00 24 100.00 21.66 33.33 722 1.67 111 036 036 7. 339 16.67 4.16 . Obeaaat ol Ike ^Circulatory System - pentaovascuhr Dbaam 430434 Cirrhosis ol Urar 571 ChoWthiBa. . CholecystR'n mt\ "ChotafiHl-r-r*''- '* ~*r.,vvrt? -*. 57457jiV Aeddmts, PoiwWru.'. and VWpw?r-'^v-` EBOOE999 249 8.90 42 129 7 02* 144 5.79 j*AN Qtte Canaa DRatidiaf - -. a , -vrysf-fy, sr i ? . . V. .`s ^ st 372 1034 030 039 4 739 . centrated in digestive system cancer, given the large number of deaths (31% of all cancer deaths). For each of the sites within the digestive system, observed numbers of deaths are greater than ex pected. Although, except for intestinal cancer, the observed num bers of deaths are small. The PMR for liver cancer is rather high, out a definite conclusion is difficult with only six observed deaths. On the other hand, the PMR for cirrhosis of the liver suggests a deficit in mortality from that cause. For white women, the PMR for total cancer appears high, as it did for white men, with cancer of the digestive system and, perhaps, cancer of the breast contributing a fair amount to the ex cess. The PMRs for individual sites within the digestive system are based upon small numbers but suggest an increase in intestinal cancer. The PMR for urinary cancer, though based upon only 11 deaths, seems strikingly high and may be an indication for further investigation. On the other hand, in contrast to the observation in white men, the PMR for respiratory cancer among white women is very close to unity. Similar to the 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 circulator) system account for a large percentage of total deaths. In eacl case, observed numbers of deaths are close to expected. Then appears to be a somewhat different pattern among men ant women for deaths due to accidents, poisonings, violence with th< number of deaths somewhat low among men and high amon] women. There were 39 cancer deaths among nonwhite men, somewha greater than expectation, although the numbers by site are toe small for meaningful analysis. Mortality from cerebrovascula disease appeared high (PMR 2.11) but the finding was baset upon only 19 deaths. Discussion The present study was designed with two objectives. The firs was to determine whether or not any angiosarcoma deaths hai 626 Mortality Among Employees of PVC Fabricators/Chiazze, Nichols, and Won 25IGSC03 BFG38854 Corn > DmU> All Canon Buccal Cavity and Ptnrynx OiiestiM System Stomadi Intntma Rectum Liver Respinteiy System Tbh 6. -- ObMtvtd nd Expend Derth* hr Sthend C*uw* Amoef Emphytd t 17 PVC Fabricators by Sex, WhKt Only, 1964-1973. ICOA (X Ruv. 140-709 Expuetto 6(6 561.997 1.19 1S1 Famulu ExpacM 137.699 140-149 150-159 151 153 154 155 160-163 16875 049 209 162 143 1.29 31.507 130 52.528 139 19.631 137 4.190 1.43 205 176557 1.14 1896 35.342 4 981 15344 3.677 0.633 11888 U1 lit 150 161 156/ 206' i.oo: --.loi^.-- * PMt is the nt of observed to needed utiere the expected nuitw is calculated on the Oasis of the dntntxitmn of deaths hr tta Met U5 el 1968 specific ht color, sex. cause, and Ife. occurred among employees of the PVC fabricators under study. Since no angiosarcoma deaths were found among the employees studied, the first question has an unequivocal answer. A secondary objective was that of examining the distribution of deaths by cause among the employees under study. Implicit in that objective is the question of whether or not that distribution is, in some sense, unusual. There is no unequivocal answer to the latter question. Whether or not an observed distribution of causes of death is unusual clearly relates to the standard or comparison population as well as the analytic methodology.* On the basis of a proportionate mortality analysis, there appear to be excesses in total cancer mortality among both white men and white women in the study, when compared to the distributions of deaths for the total United States specific for color and sex and adjusted for age. Excesses in cancer mortality appear concentrated in cancers of the digestive system and, in particular, in cancers of the intestine for both men and women. In addition, there is a suggestion that mortality from cancer of the breast and urinary organs among white women employees is higher than that for the total U.S. There are, however, several reasons why Journal of Occupational Medicine/Vol. 19, No. 9/September 1977 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.9 In addition, an analysis using PMRs fails to take account of the absolute risk of dying in the population under study.4 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 * 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.4 Results of that study suggest a possible excess in total cancer mortality, primarily cancer of the BFG38855 liver. However, there was a suggestion that cancers of the lung and brain also appeared with excess frequency. The current study, while suggesting an excess in total cancer, particularly digestive cancer, does not clearly point to marked excesses for cancers of the liver, lung, and brain among white men. although the PMRs for these cancers are greater than one. The observed-to-expected PMRs reported by Monson for vascular lesions affecting the cen tral nervous system, circulatory diseases, and external causes are similar to those reported here. Tabershaw and Caffey, in a study of workers engaged in the manufacture of vinyl chloride and its polymers, conclude that no specific cause of death was statistically significantly greater than expectations based upon Standardized Mortality Ratios (SMRs) using the U.S. male population as the standard.' By other criteria, however, the authors conclude there may be an excess risk for mortality from digestive cancer, respiratory cancer, cancer of other and unspecified sites, and lymphomas. At lower exposure levels, they suggest some excess for cancers of the buccal cavity and cancers of the other and unspecified sites. The current study would seem to indicate that excesses of mor tality from cancer of the digestive system are not sex-specific and are not limited to liver cancer. The majority of the PMRs for cancer among both white men and white women are in excess of unity. Such results must be interpreted with caution but, since they ap pear to be consistent with previously studied workers, they suggest the need for continued investigation. Summary ' Results of a study of 4,341 deaths occurring among current and former employees of 17 PVC fabricators during the period 1964- 1973 are presented. The study was carried out to determine whether any angiosarcoma deaths had occurred among em ployees of these fabricators and to examine the distribution of deaths by cause. No angiosarcoma deaths were found among the study population. Distributions by cause of death among white male and white female employees were compared with those for the entire U.S.. specific for color and sex and adjusted for age by 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 mortality 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 study was sponsored by the following organizations: American Can Company. B. F. Goodrich Company. Diamond Shamrock Corporation. Firestone Tire and Rubber Company, Johns ManviJIe. Motor Vehicle Manufacturers Association. Stauffer Chemical Company, Union Carbide Corporation. Uniroyal. Incorporated. References 1. Selikoff I) and Hammond EC (Eds.): Toxicity of vinyl chloride -- polyvinyl chloride. Ann NY. 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. Govt. 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. IOM 18:169-170, 1976. 5. Redmond CK and Breslin PP: Comparison of methods for assessing oc cupational hazards. IOM 17:313-317, 1975. 6. Monson RR. Peters |M, and lohnson MN: Proportional mortality among vinyl-chloride workers. Lancet 2:397-398, 1974. 7. Lloyd |W and Ciocco A: Long term mortality study of steelworkers: I Methodology. IOM 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. IOM 14:621-629 1972. 9. Tabershaw IR and Caffey WR: Mortality study of workers in the manufacture of vinyl chloride and its polymers. IOM 16:509-518, 1974. ro C'l 'Jr Cw o o 628 Mortality Among Employees of PVC Fabricators/Chiazze, Nichols, and Wong BFG38856