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Journal of Occupztional Medicine ( I S S N 0096-1736) Editor LLOYD 8. TEPPER, M.D. dateEditor ROBERT R. 1. HILKER. M.D. E x m t i v e Editor W R l S L. FLOURNOY. M.S. Editorb1 Board CHARLES E. BECKER. M.D. H. DEAN BELK, M.D. PATRICIA Y. HACENDORN. M.D. HENRY R. HERBERT, M D. BRUCE W. KARRH. M.D. PAUL KOTIN. M.D. THOMAS A. LINCOLN. M.D. BRIAN MacMAHON. M.D. J.4UES W MITCHELL. M.D. t . : DAVID 8. ROBBINS. M.3. ' Produdion Manaqcr , i LUCILLE ROBERTS q'g:. Manuscript Coordinator BARBARA VASUMPAUR circulation Manager VlDA HEPLER 1) . fhc Journal of Occupational Medicine is awned. copyrighted, and published monthly by the American Occupational Medical Association, 150 North Wacker Dr.. Chicago, I1 60606. Second class . postage paid at Chicago, IL. Title ~oisteredU. nited States Patent Office. SmSubscriptions: 525.00 per year. US; per year. Canada and elsewhere. Single Copies 53.50. Allow four weeks for first issue. Publisher cannot assume respow 1 sibility for replacing undelivered issues, or ! &sues damaged in transit unless notified not later than the end of the second momh following the month of issue. AJthough all advertising material acm o t 4 is intended to conform t o ethical 1 M i c a 1 standards, acceptance does not ! ~ P IeVndorsement by the Journal. ' Change of Address: Notices should in: clude old address as well as new. Attach label from recent issue if available. Be lure t0include zip codes for both old and maddress. Allow four weeks for change to become effective. Manuscripts submitted for publication should be sent to Doris Flournoy, Exe u t i w Editor, Journal of Occupational CHARLES El. SLACK. INC. Thorofare. NJ 08086 (6091 848-1oOo Marketing Director RICHARON. ROASH POSTMASTER: 'lea* send Form 35i9 to Journal of Occupational Medicine. 150 N. Wacker Chicago, IL w -~ October, 1981 Vol. 23 No. 10 ORIGINAL ARTICLES Cancer Mortality of a Group of Canadian Workers Exposed to Vinyl ChlorideMonomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. Theriault, M.D., Dr.P.H., and P. Allard. M.D., MSc. .671 Mortality Among Rubber Workers Ill. Cause-SpecificMortality, 1940-7978 . . . . . . . . . . . . . . . . . . . . . . . . Elizabeth Delzell, S.D., and Richard R. Monson, M.D. .677 Reproductive Hazards of the Workplace. . . . . . . . . . . . . . . . . . . . . . . . . . L. E. Sever. Ph.0. -Diagnostic Sensitivity Bias An Epidemiologic Explanation for an AFparent B;;lin Tanor Exes . . . . . . . . . . . . . . . . . . . . . . . . . . Peter Creenwald, M.D.. et a1 .685 .6?0 Tuberculosis Surveillance of Hospital Personnel . . . . . . . . . . . . . . . . . . . . .695 JohnV. Caeurnan, M.D. Effects of iron and Ascorbic Acid Supplementationon Hemoglobin Leveland Work Efficiencyof Anemic Women. . . . . . . . . . . . . . . . . . . . .699 Cecilia A Florencio, Ph-D. CURRENT COMMENTARY Respondingtoa Health Crisis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Richmd M. Cooper, 1.D. 705 DEPARTMENTS Letters-to-the-Editor Follow-up of Methylene ChlorideStudy ........................... A Medical Decision Only? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6tX .660 661 OMForum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664 B o o k Reviews HandlingChemicals Safely1980 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Occupational Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Woods Injurious to Human Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . White Collar and ProfessionalStress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .667 .667 .668 .669 Selected Reviews from the Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . .710 ~ Association Affairs Summary of the Meeting of the Board of Directors . . . . . . . . . . . . . . . . . . .714 General PeopleandEventc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Classified Advertising. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Classified Ads also appear as display advertising. See Advertisers' Index.) Advertisers' Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718 ,720 .724 MANUSCRIPTS. Contributors are reouested to read lnformatron ior Authors. which i s p u b lirhed in the lanuary. May and September !)sues 01 the journal and which may be obtamed from the Editorial Otilce upon request Failure to iollow the guidance conrJined therein rndv cause delav in t h e c o n < ~ d e r a r i o nor rnJnu(crtnr\ tor ntihlorrt*nn I I I I I i MO[Iti.i.4 i t y orkers I11. C:aAse-Specif'ic Mortality, 1940-1978 Eliwbeth Delreil, S.D., and 'diehard R. Monson, M.0. This report describes mortaiity occurring between 1940 and mid-7978 among 29,087men and women employed in a rubber plant for at least two years. Mortality parrerns for the period luly I, 7974,to luly 7, 7978,were compared to previously published findings for january 7, 7940,through lune 30,1974.Expected numbers of deaths were based on US. general population mortality data There were excess deaths from bladder cancer and leukemia among white male union members during both follow-up periods. During recent follow-up of white male union members ern pIoyed fora t lean five years, there were exce5ses in deaths from three additional cancers: esophageal Cancer (77 o b served1'4.8 expected), biliary and liver cancer (6 observedl 3.3 expecredl and lymphoma and multiple myeloma (14 observed/U expecrd. Evidence from other szudies of rubber workers suggem that observed eycesses in deaths from bladder Cancer and leukemia are related to workplace exposures. The present findings suggest that occupational exposures etiologically rejevant to these diseases may not have been reduced in recent years or that sufficient time has not elapsed for such reductions to result in decreased mortality. Further investigation is required to clarify the contribution of occupational factors to ob served excesses in deaths from tancers of the esophagus and the biliary passages and liver and from lymphoma and multiple myeloma. I n 1976,Monson and Nakano' reported the mortality experience of a large group ot workers who had worked for five or more years in rubber manufaduring and who were followed from January 1. 1940.through June 30, 1974.Although there was no increase in overall mortality among rubber workers compared to the U S . general POD- From the Department of Epidemiologv. Hrrvdrd School of Public Health 677 Huntington hve. Boston. MA 02115 Supponed bv a contract with the B F Goodrich Company and the Unrted Rubber. Cork. Linoleum dnd Plastics W d e n of America Dr Delzrll wds also supmncd bv d trainetrhio from the Natoonil Instltutc at Occupational S d t e h and Hedlth ( 5 115 OH0 70%) dation, there were excess deaths from several cancers. The present study describes mortality through June 30, 1978,among these workers. In addition, men and women employed for two to four years are included in order to determine to what extent their mortality experience resembles that of long-term workers. Materials and Methods Study subjects worked at a rubber manufacturing corn pany that has operated in Akron, Ohio, since the late 7800s.The company's personnel records date from 1900 and contain information on name, demographic characteristics and employment dates. Production workers have been members of the United Rubber, Cork, Linoleum and Plastics Workers of America ( U R N Union since the late 1930s.URW records on members consist of name, social security number and sequential department changes. Company and URW records were used to enumerate all active and former employees as of July I , 1971.Detailed descriptions of this procedure have been given else- where.' ' Workers who left the company before January 1.1940,or whose company service dates covered fewer than two full years before luly 1.19f7, were not included. Because numbers were small, non-white females and non-white salaried males were also not included. The total number of eligible employees was 29,087, of whom 5,302 had worked for two to four years before July 1, 1971, and were not i?cluded in previous studies of these workers. Five study groups were defined on the basis of employment category [union member or salaried employee), race and sex. Employees were classified as salaried only if they had no record of emplovment in production lobs. There were 15,613 white male (WIM)union memoers, 1,184 nonwhite male (NWM) union members, 4,200 female union members, 4,683 salaried males and 3,377 salaried females. Company censuses in 7974 and 1979 identified 4,470 active employees among the 29,087study subjects. Exact dates of termination were not obtained for these workers, Journal Of Occuoatlonal Mpdirine/?'Il 7 7 htn i n /np+nhnr . n ? . i and duration of employment as of the close ofthe study on July1.1978. was estimated as follows. Workers active in 1971 but not in 1974 were assumed to have termirited empiovment on January 1. 1973. whiie those active in 1974 but not in 1979were assumed to have terminated on July1,1976. Workers who were active in 1971 or 1974but who died beiore the designated termination c . 3 ~were assumed to have left work on the date of death. Follow-up to ascertain mortality and to measure person-years of observation started on January 1. 1940, or the second anniversary after starting work, whichever was later, and Continued to July 1,1978. The company provided death records for active and pensioned workers, and a Social Security Administration (SSA) search identified deaths among workers not known, to' be deceased. The company and the SSA reported a total of 9.388 deaths during the period January 1. 1940. through July 1. 1978; 2.533 of these were not included in ,previously published reports concerning these rubber workers.' There were no death, disability or retirement claims or reported earnings for approximately 16% of the 26,232 subjects included in the SSA search. All subjects not known to have died before Julv 1,1978, were considered to be alive on that date. Death certiticates for 4-44(4.7%) of the reported deaths could not be located. The percentage of reported deaths with unavailable certificates varied by employment group (4.0% for WM union members to 9.5% for salaried females), by duration of employment (1.4% for workers employed 1 5 or more years to 18.6% for those employed two to four years) and by age at death (29% for deaths a t and above age 65 to 18.7% for those under 40 years of age at death]. Deaths among workers employed two through four years and deaths under age 40 accounted for 11%and 3% of the total deaths, r e spectively. Decedents for whom a death certificate could not be located were assumed to have died of unknown cause on the date reported;Underlying cause of death was coded from available death certificates according to the International Classification of Diseases, 7th Revision. For each employment group, observed numbers of deaths were compared. to numbers expected based o n relevant US. mortality rates specific for cause, age. calew dar time, sex and race. (Causespecific mortality rates for Ohio are virtually identical to those for the United States'; the US.rates were used because they are avail- able in greater detail.) To compute expected numbers, person-years of obser- vation were allocated to five-year age and calendar time categories and multiplied by corresponding US. death rates? The resulting quantities were summed over all ages and years to obtain total expected numbers. Ratios of ob served to expected numbers of deaths were expressed as standardized mortality ratios (SMRs), which are estimates in percentage form of rate ratios for rubber workers com- pared to the US.general population, adjusted for age and calendar time to the person-years distribution of the employment group of interest. Confidence intervals were derived assuming that observed numbers of death follow a Poisson distribution.' Mortality patterns for the interval covered in previous reports. January1,7950.through lune 30,1974, were corn pared to those for the period July1,1974, through July 1. 1978. These intervals will be referred to as the 1940 through 1974 and the 1974 through 1978 follow-up periods, respectively. Because no new hirees after mid-1969 were included in the study. the age distribution or personyears ior 1974 through 1978 shifted toward older ages relative to the distribution for 1940 through 1?74, and comparisons of S:.tRs between the two tollow-up p e r i d could be misleading for causes of death associated witn age. To address this issue. directly age standardized mortality rates were computed for all causes and all cancers for each employment group and follow-up period,using as a common standard the person-vears distri- bution of all employees during the years 1930 through 1978. Also, for comparisons Of site-specific cancer mortality in WM union members between the two follow-up periods, age standardized rate ratios were computed using the person-years distribution of men followed dur- ing the period 1974 through 1978. Workers employed for two through four years tended to be younger than those employed for five or more years. To facilitate comparisons of overall mortality b e tween the two duration of employment categories. all- cause death rates were standardized to the person-years age distribution oi all emplovees followed during 1940 through 1978. Results There were approximately 441,985 person-years of o b servation for WM union members, 28,729 for NWM union members, 134,397 for female union members, 770,987 for salaried males and 82,Wl2 for salaried females. Average length of follow-up was 28 years for WM union members, 32 years for union females and 24 years for NWM union- members, salaried males and salaried females. During 1940through 1978WM union members experi- enced excesses in deaths from cancers of the biliary a%)passages and liver (12% excess)and of the bladder 0 7 % ) and from leukemia flable 12 There were marked deficits in deaths from causes other than cancer and vas- cular lesions of t h e central nervous system. Bladder cancer and leukemia mortality were elevated during both follow-up periods. In addition, there were excess deaths from several cancers during 1974 through 1978 only, in- cluding cancers of the esophagus. large intestine, biliary system and liver, brain and lymphatic tissues and multiple myeloma. In the lymphatic cancer and multiple myeloma category (IOcodes 200-2031, excess mortality was cow fined to ICD codes 202-203('other lymphoma" and multi- ple myeloma: 16 observd6.8 expected deaths). Examination separately of SMRs for men employed wo through four years and those employed at least five years showed that with the exceptions of lung cancer and lymphatic cancer and multiple myeloma, cancer excesses occurred only among men who worked for at least five years. Men emploved for two through four years ex- perienced slight excesses in lung cancer (76observedn3.7 expected] and in lymphatic cancer and multiple mveloma [3 obsetvedn .9expected) during 1974 through 1978. Table 2 gives age-Standardized ra:es and rate ratios (RR)for selected cancers among men employed tor five or more years. Several patterns for causes of death included in this table are noteworthy: 1. * . f 678 Mortality Among Rubber Workers/Delzell and Monson -Table I. Mortality Among White Mala Union Members According to Cause and Follow-Up Period. Follow-Up Pwiod Causa of Oeath (IC0 No.)' 1940-1974 SMRt Obs: i974-197a SMR Obs 1940-1978 SMR Obs 95% CIS AS causes Malignant neopIasms (140-205) Digestive organs and peritoneum (150-159) Esophagus (150) Stomach (151) Large intestine (153) Biliary passages and Ii& (155, 156) Pancreas (157) Lung (162. 163) Prostate (177) Bladder (181) Brain (193) Lymphatic and multiple myeloma (200-203)1 Leukemia (204) Vascular lesicns 01 the central nervous system (330-334) Diseases of the circulatory system (400-468) Diseases of Ihe respiratory system (470-527) Diseases of the digestive system (530-587) Accidents. poisoning and violence (800-496) 3!aer known causes Deaths without cenificales I YJ ttial del!PsI e6 94 101 88 103 103 104 89 91 103 117 82 94 122 97 86 70 52 64 61 11-21: 5 5 j.: 1GS3 396 25 98 115 33 58 275 95 49 24 54 57 531 2647 246 251 328 3P5 2.7% 9G 102 113 191 107 115 179 64 81 101 115 147 183 117 83 78 88 96 62 77 fill!: 1103 259 78 11 12 29 7 9 67 26 11 7 22 11 100 463 82 43 32 63 5.5% 8: 96 103 105 103 105 112 a4 88 102 117 91 109 121 96 85 74 83 64 63 11-274 6197 1352 474 36 110 144 40 67 342 121 60 31 76 68 631 3110 328 294 360 448 40% 8 s - :- -91 *.** -94 1'; 73- 125 8 5 - 1:i 8 9 - 1:4 -80 Is! -65 ::: -79 Gs -as I: -89 1 3 -62 120 -86 13; 94 * 153 E 6 . !Z: -82. 35 -66 74 L? '33 57 - ~~~ -'International Classificationat Diseases. 7th Revision tStandardiZed mortality ratio: 100 x (observed no. af deaths expected no. of deaths), Expecled numbers are based on age-. lime-. J ~ J cause-specific death rates for U.S. white males -Sobs observed number of deaths -gCl confidence interval of SMR l C o d a 200. 202 and 203 are not included betore 1950 I .Esophageal cancer rates in WM union members tfii between the two follow-up periods, while rates for white males remained essentially unchanged. . Large intestine cancer rates rose only slightly for I W M union members and U.S. white males. Bladder cancer and leukemia rates among WM )n members did not change appreciably, nor were e marked trends in these rates for U.S. white males. 4. Other lymphoma and multiple myeloma mortality rates nearly doubled among US. white males and quad rupled among WM union members, for whom there was a greater than twofold excess in deaths from these diseases during the period 1974 through 1978. Further examination of mortality among WM union members who worked for at least five years and died in 1974 through 1978 showed that the observed excesses in -Table 2. Mortality from Selected Cancan Among Whiie Male Union Members Employed lor at Least Five Years, According to Follow-Up Period. 1 Cause of Death Esophageal cancer Large intestine cancer Follow-Up Period 1940-1974 1974-1970 Ubs' Ratof R R t Obs Rate RR 23 1.3 83 11 3.8 228 Biliary and liver cancer Bladder cancer 2.25 1.19 46 3.8 136 11 3.8 131 2.85 2.99 Leukemia 57 3.4 152 11 3.8 136 2.25 2.85 IOther lymphoma and multiple myeloma1 18 1.2 109 14 4.8 242 J1.15 2.05 'Observed number of deaths ?Rate ( X 10.000 person-years). Rates tor 1940-1974 are adlusted tor age acrorcing to the aisiribution of men employed tive or more rem ane followed 1974-:g76 $Ratio ( x loo) 01 ~:ancarciredraie in ruSber workers and slandarcaed rate in U S wh~tomales These numOers are rates ( X 10.000 personayears) tor U.S. white males. age stanaarairea to tne oistribuiion of men employed tive or more ~ C J ~ S and lollowed 1974.1978 lOnly deaths alter 1949 are included ml of Occupational Medicine/Vol. 23. No. 10/0ctober 1981 679 *ai _- .. :..-..*: .+:.. .-_ -Table 3. MOfWty Among Non-White Male Union Members According to Cause and Follow-Up Panod. 1 Causa of Darth (IC0 No ) All causes Malignant neoplasms (140-205) Digestive organs and pentoneum (150-159) Esophagus (150) Stomach (151) Large tnt!mne (153) Biliary passages and liver (155.156) Pancreas (157) Lung (162.163) Bladder (181) Lymphatic and multiple myeloma (200-203)t Vascular lesions of the Central nervous system (330-334) Diseases of the circulatory system (400-468) Oiseases of the respiratory system (470-527) Diseases o! the digestive system (530-587) Accidents. poisoning and violence (800-998) Other known causes Deaths wiihout certificates (% total deaths) 1940-1974 SMP' om 65 251 77 45 82 17 81 3 80 5 55 2 154 3 123 4 83 13 00 15458 242 79 106 38 8 28 5 55 28 46 29 n=8 3.2'4 Follow-Up Period 1974-1978 SMA 3es SM.~ 82 72 91 18 121 7 81 1 68 80 90 81 00 66 155 2 81 249 1 170 272 3 160 46 3 72 269 1 56 215039 92 17615 82 26 83 85 4 46 116 5 45 25 2 51 19 2 42 1116 83% n=14 1940-1978 obs 953, CI 323 63 24 4 61 62 58 22 ---- 76 103 135 207 5 21-154 -4 4 22 46 -- 209 436 7 16 64 41 - 331 117 1 1-311 316 6424-- 37922 132 67- 94 -12 24- 81 10 30 21 35 - 82 73 31 40% I1 'Expeiteo c imotrs for SMRs are oased on age-. calencar rime-. and cause-specitic death rates :r U.S. non-white males Nodes 200. 202. ana 203 are not incruded before 1950 esophageal cancer and other lymphoma and myeloma concentrated among men who started working between 1935 and 1950 (esophageal cancer: 7 observd2.3 ex- pected other lymphoma and multiple myeloma: 7 o b servedl2.5 expected) and who worked forat least10 years and died 30 or more years after starting work (esophageal Cancer: 7 1 obsemd/3.8 expected; other lymphoma and multiple myeloma:14observd4.7 expected).Preliminary analysis of mortality by work area for all WM union m e m bers revealed excesses in other lymphoma and multiple myeloma among men employed for five or more years in the following divisions (observed deathdexpected deaths based on rates in US.white males): aerospace (5/2.6).r e claim (4/0.7),and hose and belt (7/3.0)E.sophageal cancer was elevated in men who worked for at least five years in rubber reclaim (510.9). Mortalityfrom all causes among NWM union memben Vable 3) was 32% lower than expectedduring the overall study period. Although mortality from most specific causes was also lower than expected, there were excesses during both follow-up periods in deaths from cancers of the biliary passages and liver, pancreas and lymphatic -Table 4. Mortality Among Female Union Members According to Cause and Follow-Up Period. Follow-Up Period Cause of Osath (IC0 No.) All causes Malignant neoplasms (I40-205) Digestive organs and pentoneum (150-159) Stomach (151) large intestine (153) Biliary passages and liver (155. 156) Pancreas (157) Lung (162.163) Breast (170) Uterus (171-174)t Cervix (171) BlaCdodrpeur s(1(8117)2) Brain (193) Lymphatic and multiple myeloma (200-203)t Leukemia 1204) Vascular leslons of the central nervous system (330-334). Diseases of tne cirtularory system (440-468) Diseases of the reswatory sysiem (470.527) Diseases of the dqosiive systei (530-587) A0:chcerioeknntso.wpnocisaoursrensc an6 violence (6OC-998) Deaths withoul certificates (% total deaths) 1940-1974 SMR' Obt 79 730 a2 205 75 52 74 8 92 26 106 8 38 4 97 16 84 47 19592 30 21 12507 25 102 6 88 10 87 7 7p 69 73 250 72 23 74 32 8516 3686 n-47 6.4% 1974-1978 SMR Obs 85 57 43 90 36 70 0 26 75 181 123 223 0 ,223 30 49 81 76 125 103 113 65 n=27 233 36 8 2 3 1 0 2 9 7 2 5 0 3 1 1 28 92 16 10 9 15 1 1 6% 1940-1978 SMR Obs 95% CI 7870 69 924613 60 6758 52 --- 8857 88 77 79 100 10 29 9 34 53 46 --- 142 114 190 28 4 8 - 73 -75 18 4 4 - iia 03 56 62 107 108 149 58 119 124 3237 7 5 79233586---- 122449 120 278 9 57 - 236 :7 79 73 74 87 79 11 8 97 342 39 42 37 34 59 66 62 Si ----- 133 156 69 82 119 107 65 47 62. 112 56 81 n-74 7.6% 'betted numbers for SMRs are based on age-. calendar time-. ana cause-specific death rates tor U.S. white females tCodes 171. 200. 202 and 203 are nat inciudea before 1950 680 Mortality Among Rubber Workers/Delzell and Monson -Table 5. Mortality Among Salaried Males According t o Cause and Follow-Jp Period. Causa of Death (ICC No.) All causes Malignant neoplasms (140-205) Digestive organs and peritoneum (150-159) Esophagus (150) Stomach ( 151) Large intestine (153) Biliary passages and liver (155. 156) Pancreas (157) Lung (162. 163) Bladder (181) Brain (193) Lymphatic and multiple myeloma (200-203)t Leukemia (204) Vascular lesions of the central nervous system (330-334) Diseases of the circulatory system (440-468) Diseases of the respiratory system (470-527) Diseases of the digestive system (530-587) AccidenIs. DOlSOning and violence (800-9981 C:w w w n causes Dearns without cenificates ( % Iota1 deaths) 1940-1974 m a - obs 75 77 72 76 77 68 18 73 81 120 97 110 99 75 71 51 51 -.3-6. "- ns47 866 167 51 4 13 14 1 9 48 9 6 13 9 73 406 33 31 41 63 5.3% Follow-Up Period 7914- 1978 s m Obs SMR 69 59 101 146 39 105 337 31 50 49 74 67 :5 64 66 128 25 59 51 n=12 198 35 16 2 1 6 3 I 10 1 1 2 1 15 88 26 3 7 12 6.1% 70 72 77 90 72 76 61 64 73 195 93 101 38 73 70 69 4-.-7 -I -5 n=59 1940-1978 Cns 95.. E' 1064 202 67 6 14 20 65 - 7 ; -63 93 -60 ?8 -3 3 . '46 39 121 4:. :'$ -4 1 6 - !I5 10 31 119 58 56 95 ~ -10 5 0 - '?? 7 3; ' ? I 15 5;- ' f i 10 -1:. .52 88 53 +J ~ -494 64 - ;d 59 53 54 34 33. @6 48 2 7 . 2. 80 5.5% 'Expected numners for SMAs are based on age-. calendar time-. and cause-speclflc neath rates for u.S. white males ?Codes 200. 202 and 203 are not included betore 1950 tissues and multiple myeloma. Lymphosarcoma, reticule sarcoma and Hodgkin's disease were responsible for the excess mortality in the lymphatic cancer and multiple myeloma category. There were no leukemia deaths, while two were expected during the overall study period. The 2l% excess in digestive cancer deaths for the period 1974 through 1978 was accounted for by cancers of the large ntestine, biliary passages and liver and pancreas. Among female union members (Table4,there were ex- zesses in deaths from cancer of the cervix, bladder and )rain during 1940 through 1978. For most other causes, :here were deficits in observed deaths, with SMRs ranging from 28 for pancreas cancer to 100 for cancer o i the biliary passages and liver. Excesses in bladder and brain cancers were based on five and nine observed deaths. respectively. The increase in bladder cancer mortality seen only in the years 7940 through 1974, while the brain cancer excess occurred only in the years 1974 through 1978. There was no excess mortality from respiratory cancer, even among women who worked for at least 20 years (6 observed/8.8 expected). Excess cervical cancer deaths occurred during both follow-up periods. Further analysis of the cervical cancer deaths showd that elevated mortality was confined to women who were -Table 6. Mortality Among Salaried Females According to Cause and Follow-up Period. Cause at Death (IC0 No.) All causes Malignant neoplasms (140-205) Digestive organs and peritoneum (150- 159) Lung (162. 163) Breast (170) Uterus (171-174)t Cervix (171) Corpus (172) Bladder (181) amin (193) Lymphatic and multiple myeloma (200-203)t Leukemia (204) Vascular lesions of the central nervous system (330-334) DDiisseeaasseess ooff tthhee creirscpuilraattoorryy ssyysstteemm((444700--456287)) D i s e i : ~13the C:ces:ive c.'p.;zm :j??.j87l A C X S i S . P O i S C f i i ~an~ 0 violence (6c3.33) Other known causes Deaths Wi[hOut certificates (% total deaths) 1930.1 974 SMR' Obs 75 192 89 65 106 17 74 4 90 16 45 4 20 1 39 1 282 2 135 3 161 6 38 1 68 15 61 47 55 5 66 3 62 14 49 18 n119 9.9% Foilow-Up Period 1974-i970 SMR Obs SMR 56 51 83 0 100 .0 0 0 0 0 78 0 58 51 26 23 1ij 26 1354 49 13 5 0 6 0 0 0 0 0 1 0 5 16 1 1 6 3 8.2% 70 79 100 45 93 47 17 30 200 103 12; 29 65 58 25 56 it 46 n=23 1940-1978 Ohr 95% C I -241 62 80 -78 62 98 23 63. 150 -4 12 115 -22 58 140 -5 15 110 1 0 - 94 1 0. 168 2 23. 733 3 21 . 300 7 56-:Y: -1 1 . 162 20 39 100 63 4 5 . 74 6 1:. ion 10 ?7.1....1 20 4.3. t i . ! 21 9.5% 'Expected numbers for SMRs are base0 on age-. calendar tlme-. and cause-speclflc ceaih rates for U.S. white ternales tcodes 171. 200. 202 and 203 are not included betore 1950 Oufnal Of Occupational Medicine/Vol. 23. No. IO/October 1981 i -Table 7. Mortality from Ail CIUStS and from All Cancers According to Employment Group and Follow-Up Period. ~~ Fdlow-Up Ptfliod ?440-1974 1974-1976 Emoloymant Grouo Strndardirtd 05s Cruor Rate' Ratrt Standardized Obt Cruet Rate' Rate , white male union mern9e:s All causes All cancers Non-white male union members All causes #I1 cancers Female union members All causes All cancers Salaried males AI1 causes All cancers Salaried lemales AH causes All cancers 5694 14.1 13.8 (0.2)$ 1103 29.1 13.8 (0.6) 1093 2.7 2.6 (0.1) 259 6.8 3.2 (0.3) 251 10.0 14.7 (1.0) 44 1.7 2.5 (0.4) 72 20.1 15.7 (2.0) 19 5.3 3.8 (0.8) 730 6.0 6.7 (0.3) 233 17.9 6.1 (0.5) 205 1.7 1.8 (0.1) 36 2.7 1.1 (0.2) 366 9.0 11.3 (0.4) 198 . 13.3 70.0 (0.7) 167 1.7 2.2 (0.2) 35 2.4 1.8 (0.3) 192 2.8 6.5 (0.6) 65 0.9 1.9 (0.3) 49 13.9 13 1.o 4.3 (0.6) 1.1 (0.3) ' C ~ d eannual rate (x 1.000 person-years) tAnnual mortality rate (x 1.000 person-years). stancardized for age to the oerson-years distribution of all employees followed 1940-1978 SNumDers in parenthescs are standard errors (x 1.O?O person-years) of the standardized rates employed for at least 15 years (16 observ46.7 expected), who died 25 or more years after starting work (15 o b serveG.6 expected) and who started work before 1940 (16 observd8.1 expected). The uterine cancer SMR for union females increased from 99 in the period 1940 through 1974 to 181 from 1974 to 1978. This change resulted from a marked decline in age-adjusted uterine cancer death rates for U.S. white females from 5.7 per 1O.ooO person-years in 1940 through 1974 to 29 per 10,OOO person-years in 1975 through 1978,' while similarly age-adjusted rates for union females changed only slightly from 5.9 to 5.2 per 10,OOOperson-years during the same intervals. Compared to US. white males, salaried males (Table 5] experienced no increased mortality during the overall study period. For the period 1974 through 1978 there were excesses in deaths from esophageal and biliary and liver cancer, based on two and three deaths, respectively, and a 28% increase in deaths from diseases of the respiratoq system. For salaried females (Table 61, there were excesses, based on small numbers, in cancers of the bladder, brain and lymphatic tissue and multiple myeloma These oc- curred only during the earlier follow-up period. The deaths from cancer of the lymphatic tissues and multiple myeloma were from Hodgkin's disease(2 observedfl.1 ex- pected) and from other lymphoma and multiple myeloma (4 observedn2 expected). In contrast to union females, salaried females experienced a marked deficit in cervical cancer deaths during both follow-up periods. Table 7 gives all-cause and all-cancer age-adjusted mortality rates for each employment group. NWM union members experienced the highest overall mortality rates during both follow-up periods and the highest cancer mortality rate for the years 1974 through 1978. All-cause and all-canter mortality rates either increased slightly or EmplDymrnt Group/ Ouranon of Emplqrmrnt (Yrt.) While male union members 2-4 25 Non-whik male union members 2-4 25 Female union membea 2-4 25 Salared males 2-4 25 Salaried females 2-4 Obr 730 6067 40 284 120 843 101 963 50 Crude flab' 7.8 17.4 6.2 12.7 3.3 \ 8.6 3.7 11.6 1.3 Standardlrrd ktrt 13.0 (0.5)$ 13.8 (0.2) 20.9 (6.D) 14.8 (0.9) 4.5 (0.4) 7.1 (0.2) 8.8 (1.01 11.2 (0.4) 3.9 (0.8) , 682 MortalityAmong Rubber Workers/Delzell and Monson -. remained unchanged during the two follow-up periods for W M and NWM union members and decreased for female union members and salaried emplovees. Except for the sharp drop in cancer rates in females, these trends are consistent with patterns observed in the general population. The approximate 40% decline in cancer mortality rates among female rubber workers was not paralleled bv a similar decrease in cancer mortality rates for U.S. white females, which fell less steeply from about 2.4 per 1,oOO person-yearsinthe period 1940 through 1974 to about 2.2 per 1,OOO person-yeanwin1975 through 1978.' For union females the percentageof reported deaths in which cause of death could not be determined because of missing death certificateswas nearly two times higher in the years 1974 through 1978 than from 1940 through 1974. This difference may have contributed to the decline in their cancer SMR (Table 4) and rate between the two follow-up periods. However, cancer SMRs corrected by distributing deaths with missing certificates by cause according to the distribution of certified deaths were 88 for the period 1940 through 1974 and 64 for 1974 through 1978. It is therefore unlikely that failure to locate death certificates ccmp4etelv exdains this finding. Except for WM and NWM union members, workers employed for two to four years experienced lower overall mortality than those employed for at least five years Fable 8). Among WM union members, rates were similar in the h+o duration of employment categories. NWM union members who worked for two to four years experienced higher overall mortality than men who worked for five or more years, although the magnitude of the standard errors of the rates suggests that this difference is consistent with sampling variability. Numbers of deaths from specific causes among short-term workers were generally insufficient for meaningful analysis. Apparent excesses in deaths from certain cancers amongW M union members employed for two to four years were mentioned earlier in this paper. Discussion The present study evaluated mortality occurring be tween January1.1940. and luly 1.1978, among 29,087 men and women who worked for at least two vears at a large rubber manufacturing facility. These woriiers have now been observed for an average of 27 years per employee. Eiefore discussingspecific findings based on their mortality experience, it is important to note several limi- tations imposed by the methodology used in the study. First SMRs and RRs reported in this study are probably conservative estimates of causal associations, if any, b e tween rubber industry employment and specific diseases. Failure to identify all deaths during the study period, unavailability of death certificates for nearly 5% of the reported deaths and use of the U.S. general population as a comparison group are likely sources of underestima- tion.' Lack of information on disease determinants other than employment and demographic characteristics cow stitutes another limitation oi the studv. Without this information. it is difficult to judge whether observed dssociations reflect causal links between disease and workrelated exposures. Finally, many cause-specific SMRs were bdictc on small numbers of events and were statisticallv uflzt3hk. Therefore, sampling variability cannot be discounted Y an explanation for some of the observed e \ i ~ ~ + .dni deiicia. especially among employment groups o : w :fa? the WM union members. For this reason, the remJlnlrS discusion will focus on findings in the latter ~ : .c5.-:-:* Reports' a concerning mortality during 1%) :h:%iY 1974 among the rubber workers included in this S U A noted excess deaths from the following cancers: (11b l ~ d - der cancer and leukemia in W M union members: 13hm phatic cancer and multiple myeloma in N b ' M unim members; (3) cervical cancer, bladder cancer .and I\ n+ phatic cancer and multiple myeloma in females; m d i.ll lymphatic cancer and multiple myeloma in salaried males. Among females there was excess cervical cancer only in union members, and excess lymphatic cancer and myeloma occurred only in salaried ernplo\ees. T t x results of recent follow-up through mid-13.8 + u W i t several additional findings. Among W M union members, neither SMRs nor directlv standardized rate ratios for bladder cancer and l e u k m u changed apDreciabiv between :he two f ~ i l ~ - out'rpiods. indicating that the excesses oi these diseases anionr: rub ber workers have not diminished in recent years. Se\erJI explanations are possible: (lth)ere have been no rductions in oculpational exposures associated with these cancers; (2) sufficient time has not elapsed for such reductions to result in decreased mortality; and (3) persistent differences in nonoccupational risk factors tor these malignanciesexist beweenrubber workers and US.white males. Several studies have identified smoking as a deter- minant of bladder cancer.' * lo Emphysema and lung cancer are also strongly positively associated with smoking, and mortality from these diseases would be elevated among the rubber workers in this study if they smoked more than the general population. However, WM union members experienced deficits of 14% and 16% in lung cancer and emphysemadeaths, respectively, and it is thus unlikely that they smoked more.than u.S. white males in general. W M union members employed fbr at least five years experienced twofold excesses in deaths from esophageal cancer and from other lymphoma and multiple m t t h m a and an 80% increase in biliary and liver cancer mortality during the period luly 1, 1974, through ~ u l y1, 1978. AI- though previous studies of rubber workers noted in- creased mortality from stomach and large intestine cancer' l1 lZ1J and linked these excesses to occupational exposures,311l4ls there have been no prior reports of elevated esophageal cancer among rubber industry em- ployees. Alcohol and cigarette consumption are the ma- jor known risk factors for this malignancy. However, evidence cited above suggests that rubber workers in this study did not smoke more than the general population. and a similar argument can be advanced agnirist the possibility of higher alcohol consumption among rubber workers: WM union members experienced a 17% deticit in dearhs from diseases of the digestive SVStern. .ind the overall S M R for cirrhosis. which i s strongly a>roci.\td with alcohol intake, was 79. Mancuso and Brennan" suggested that gallbladder Journal of Occupational Medicine/Vol. 23. No. 1O/October 1981 683 and bile duct cancers are increased among rubber work- ers. To support this h v p o t k i s , they pointed out that ttie rubber industw employs numerous hepatotoxic agents and that several nitrosamines chemically related to sub stances used in rubber manufacturing have been shown experimentallv to be liver and Siliary carcinogens Gliiar) and liver cancer mortality rates among WM union mem- bers in the present study rose only slightly between the Triadtwo follow-up periods, and the marked increase in SMR seen for the 1974 through1978 resulted almost en- tirely from a sharp decline in rates for US. white males after 1%9 that was brought about partly by changes in rules for classifying this cause of death." It is possible that procedures for diagnosing, reporting or coding biliary and liver cancer as a cause of death among study d e c e dents differed in some way from those used for general population decedents. Such differences, if present. could account for the excess seen during recent follow-up. Among the cancers of the hematopoietic and lyrnphat- ic tissues, leukemia has been the subject of much investi- gation in the rubber industrv, where exposures to indus- trial solvents probably produce excess leukemia mortali- ty.'lo Our findings and those of orher investigators sug- gest that lymphatic cancerr and multiple myeloma may also be elevated in rubber workers. Little is known about the etiology of the various lymphatic cancers and multi- ple myeloma. Associations cupational groups exposed htoavechbemeeincalrse,p"orate*d' for oc- and to radiation." Is In conclusion, results of recent follow-up were COP sistent with mortality patterns previously described for these workers' and for other groups of rubber work- ers.""1'1~* Compared to their general population coun- terparts, men and women employed in the rubber indus- try experience deficits in overall deaths and in deaths from most specific causes but sustain increased mortality from several cancers. 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