Document 01dERDROdO6z89px9N0KjRyO

\ Monsanto _____________________________________________________________ DEPARTMENT OF MEDICINE a ENVIRONMENTAL HEALTH Monsanto Company. 8 0 0 N. L in d b e r g h B o u le v a rd St. Louis, M issouri 63166 Phone: (314) 6 9 4 - 1 0 0 0 September 15, 1982 Mr. David P. Brown Assistant Chief Industrywide Studies Branch NI0SH 4676 Columbia Parkway Cincinnati, Ohio 45226 Dear Dave: Enclosed is the Zack and Musch paper that we discussed over the telephone. Any final draft of this will differ in the background section but not in the numbers in the tables. Since EPA has this draft and since it was referred to in EPA's mini-symposium I see no problem in summarizing the results for Dr. Wade, but I would prefer that you not send him a copy just in case a slightly different version gets published. Yours sincerely, aw Enclosure William R. Guffey, Ph.D. Manager, Epidemiology A Retrospective Mortality Study of Polychlorinated Biphenyl Manufacturing Workers^- Judith A. Zack, M.P.H.2 David C. Musch, M.P.H., Ph.0.3 ^Monsanto Company Department of Medicine and Environmental Health ^Present address: 1751 Legend Lane St. Louis, MO 53141 ^Present address: Department of Ophthalmology University of Michigan Medical School ST2512 Scott Turner Bldg., Box 004 1010 Wall S tre e t Ann Arbor, MI 48109 J u d i t h A. Zack/Page Z Abstract A retrospective cohort mortality study of workers exposed to polychlori nated biphenyls (PCBs) during production of the compounds is reported. A total of 89 workers exposed to PCBs for a minimum of six months during the period from 1945 to 1965 were followed through 1977, and t h e ir vital status was deter mined. Comparison of th is PCB-exposed cohort's mortality experience with age-, race-, and cause-specific mortality rates of the U. S. male population was performed. Observed deaths were not s t a t i s t i c a l l y greater than expected for any of the cancer s i t e s examined. No deaths were observed for cancer of the liv e r or malignant melanoma. A s t a t i s t i c a l l y sig nificant excess of circulatory disease deaths, exclusive of a r te r io s c le r o ti c heart disease, was observed in white males. 9 -* J u d i t h A. -Zack/Page 3. The term "polychlorinated-biphenyls" (PCBs) describes a group of mixed chlorinated biphenyls which vary in consistency from li g h t , free-flowing * liquids to crystalline and non-crystalline solids, depending on the degree of chlorination. PCBs have been in commercial use since 1929. Their d ie le c tric properties, resistance to-oxidation, acids, bases, and other chemicals, and thermal s t a b i l i t y have made them useful for many applications, particularly in the production of capacitors and transformers, and in the insulation of e l e c t r i c cables and wires. Reports of adverse health effects in man i n it ia t e d from several incidents of accidental heavy exposure to PCBs. A process change in a chemical- plant introduced an unspecified PCB compound (Arochlor) into the work environment, resulting in exposure of 14 workers to estimated breathing zone PCB levels of 0.1 mg/m^.l Chloracne developed in one-half of the exposed workers, and liver, function t e s t s showed a-borderline abnormality in one of the seven affected workers. After 13 months of follow-up, the chloracne had disappeared, but the l i v e r function* abnormality ' although improved, remained. Accidental ingestion of rice oil contaminated with PCBs has resulted in several outbreaks of common symptomatology,, reported from Japan ("Yusho" disease)2 and Taiwan `("Yu-Cheng" disease).3 The most common acute symptoms observed were hyperpigmentation and acne-like le sions, discharge from the eyes, neuroendocrine disturbances, emesis, and diarrhea. There was a dose-response relationship between the amount of oil ingested and the proportion of persons reporting symptoms. After six years, many of the patients s t i l l reported such symptoms as headache, stomach pain, numbness of<the extremities, a r th r a lg i a , ' and r e s p i r a t o r symptoms.4 Although massive ingestion of PCBs occurred in these incidents, analysis of the cooking oil in the Yusho episode showed that J u d i t h A. Zack/Page 4 polychlorinated dibenzofurans^ and polychlorinated quaterphenyls were cocontaminants. Analysis of blood samples from patients in both incidents, as well as l i v e r and adipose tissue from Yusho patients, showed the presence of these compounds along with PCBs.? 8 These co-contaminants obscure the r e l a tionship of PCBs to the symptoms resulting from ingestion of the contaminated rice oils. The Yusho incident served as a stimulus to a large number of toxicologi cal studies dealing with the health effects of PCBs- Chronic toxicity studies of PCBs in mice and ra ts have shown hepatic effects ranging from hyperplasia to w e ll-d ifferen tia te d hepatocellular carcinomas 'following the ingestion of various PCB-containing diets.? 1 Studies of human exposure to PCBs have shown that body burdens are directly related to the level of exposure to PCBs.H* 13 Morbidity-studies have focused on the effects of PCBs on the skin, li v e r , blood chemistry, and other systems.13, 16 Chlcracne, dermatitis, mild liv e r func tion abnormalities, -and increased triglycerides levels were reported with some consistency from these studies - Mortality studies of occupationally-exposed individuals have not yielded consistent r e s u l t s . A preliminary report*? addressed an increase in deaths due to malignant melanoma (2 obs. vs. 0.04 exp.), which occurred in a group of 51 research and development and 41 refinery workers a t a Mew Jersey petrochemical plant. Another author commented on problems in defining exposures in th is stu d y .18 In a study of 2567 capacitor plant workers exposed to PCBs, excesses of l i v e r and rectal cancer deaths, which were not s t a t i s t i c a l l y sig n i f i c a n t , were reported. Although few deaths were available for analysis by duration of exposure and latency, there was no trend by these measures for l i v e r cancer deaths, and a s li g h t increase by latency but not by length of * V, ' 1' \ V - i i i C "iiSi'V'i? J u d i t h A. Zack/Page 5; exposure for rectal cancer deaths. Another study of 1310 workers from a capac itor-manufacturing plant with a t l e a s t six months employment between 1946 and * 1970 found s t a t i s t i c a l l y significant excess deaths from all cancers (in males! and all causes (in females).2 Suggestive, but not s t a t i s t i c a l l y significant, excesses were noted for deaths due to digestive system cancers (in males) and malignancies of lymphatic and hematopoietic tis s u e (in males and females). Ho deaths were attributed to l i v e r cancer or malignant melanoma. Due to the r e la tively young age of th is worker cohort and the r e su lta n t small number of deaths (n = 27), s it e - s p e c if i c excesses were based on two or three deaths; therefore, further study of this cohort was proposed by the authors. At about the time of the i n i t i a l report dealing with the mortality experi ence of an occupationally-exposed worker cohort, a preliminary review of the mortality experience of Monsanto workers involved in the production of PCBs was carried out. The present study represents a completed analysis of t h i s worker cohort's mortality, with particular attention given tG jw e r a ll cancer, l i v e r and pancreatic cancer, and malignant melanoma. Materials and Methods During the period from 1936 to 1977, PCBs were manufactured a t Monsanto Company's Sauget, I lli n o i s plant. Throughout th is period, the process of manufacture remained relatively unchanged. This process, in b r i e f , involved the batch chlorination of biphenyls in the presence of iron and iron chlorideca talysts. The crude"mixture produced in the chlorinators was then aerated, d i s t i l l e d , earth treated, f i l t e r e d , and transferred to storage tanks before . shipping. While no industrial hygiene monitoring data were available to quan t i f y the PCB-exposure levels during the stuoy time, interviews with plant personnel established the f a c t that PCB exposure levels did not vary consider ably within the PCB department. Therefore, all workers in t h is department 1 ' r h T " Judith A. Zack/Page ,6 were considered to have a common exposure to PCBs, as well as other chemicals used in the department, including hydrochloric acid, t r i - and tetrachlorobenzene, biphenyl, and chlorine gas. All male employees from the hourly roll who worked in the PCB department * for at l e a s t six months between January 1, 1945 and December 31, 1965 were selected for the study. By use of the plant's computerized work history system, union records, and manual work history v er if ic a tio n , 89 male, hourly employees met the c r i t e r i a for inclusion in the study. The vital sta tus of 98.9% (88) of the cohort was determined as of December 31, 1977, using standard follow-up techniques. Table 1 summarizes the resu lts of the vital s ta tu s tracing. *A death c e r t i f i c a t e .was obtained for each person found to be deceased, and coding of the underlying cause of death was performed by ar; experienced nosologist, using the International Classification of Diseases, Adapted, Eighth Revision. 21 Using a computer program developed for such an ap p lica tio n ,22 the observed number of deaths among PCB workers was compared with those expected based on age-, race-, and cause-specific mortality rates of U.S. males. To compute ex pected numbers, person-years of observation were allocated to five-year age and calendar time categories and multiplied by correspond!'ng race- and causes specific death rates for U.S. males. The resulting quantities were summed ever all ages and years to obtain the total expected numbers. Ratios of ob served to expected number of deaths were expressed as standardized mortality r a tio s (SMRs). Significance te sting of the SMRs was performed a t the 5% le v el, assuming th a t the observed number of deaths follow a Poisson d i s t r ib u t io n .23 * Results Of the 88 PCB workers for whom vital status tracing was successful, 58 were verified living and 30 were verified deceased. Death c e r t i f i c a t e s were J u d i t h A. Zack/Page 7" obtained for each of the decedents- The person-years of observation contrii buted by the en tire worker cohort are shown in Table 2- A total of 1800.1 * person-years were observed a t all ages, with the majority observed in the j middle-age range (ages 35-60 y r s . contributed 74%, or 1333.1 person-years to the t o t a l ) . Cross-classification of PCB exposure duration with vital status I (Table 3) shows th a t the majority of both living and deceased workers were j exposed less than three years. The average length of exposure to PCBs for I living and deceased workers was similar, with deceased workers having slightly j more exposure time (3.7 y r s . vs. 3.2 y r s . , respectively). i Cause-specific SMRs are l i s t e d in Tables 4 and 5 for the 60 whi'te and 29 nonwhite male members of the PCB study cohort. Deaths due to malignant neo plasms, as indicated in Table 4, accounted for 27% (8) of the total number of deaths. No cancer deaths were attributed to malignant neoplasms of the l i v e r f -- , or pancreas, or malignant melanoma. While many of the cancer-specific SMRs exceed 100, none are s t a t i s t i c a l l y signific ant. In white maT_e_s, lung cancer accounted for 75% of the deaths- due to malignant neoplasms, while no single cause predominates in nonwhite males. Table 5 presents a brief summary of the eight cancer deaths in the PCB worker cohort. Among the non-nialignant causes of death (Table 6), diseases of the c i r culatory system accounted for almost half of the deaths. For the category of circulatory system disease, exclusive of arteriosclerotic heart disease, the SMRs for white males and for the total cohort were significantly greater than 100. The excess in deaths due to this category is accounted for solely by the experience of the white males, since nonwhite males showed an SMR of 93. No other causes of death in Table 6 showed observed deaths which were s t a t i s t i c a l l y * J u d i t h A. Zack/Page. B greater than expected. The overall SMR for malignant and non-malignant causes was 131 (30 observed, 22.88 expected deaths). L i t t l e difference was found in th is overall SMR by race (for whites, 133; for nonwhites, 128). Discussion This investigation dealt with the mortality experience of a cohort of 89 male workers involved for a l e a s t six months in the production of PCBs between January 1, 1945 and December 31, 1965. The only cause of mortality which showed a s t a t i s t i c a l l y s ig n ific an t excess in observed deaths was circulatory diseases exclusive of a r te r io s c le r o ti c heart disease. This excess was apparent only for white males. Circulatory diseases in this category included deaths from rheumatic heart disease, cerebrovascular disease, and other forms of heart disease. If this excess cause of death is not an a r t i f a c t , one would postulate th a t there may also be a relation between risk factors of these circulatory diseases and PCS exposure. Blood pressure, a risk factor (when elevated) of coronaty heart disease (CHD) and cerebrovascular disease, has been related to blood PCB levels in two studies, with conflicting resu lts. One study2^ found that serum PCB levels made a s t a t i s t i c a l l y sig nificant contribution to explaining the v a r ia b ility of d ia s to lic (but not systolic) blood pressure measurements in multiple regression analyses of data from a community exposed to DDT and PCBs, while another study25 found no such association. Studies of l i p i d s , which have been associated with CHD and (with less consistency) with cerebrovascul ar disease, have considered total cholesterol, high density lipoprotein (HOL), and tr ig ly c e r id e levels in rela tion to blood PCB levels. While no consistent association has been shown between blood PCBs and total cholesterol or HDL le v e ls , most, 13> 16 but not a l l , 2^'studies have shown increased triglyceride J u d i t h A. Zack/Page 9 " levels with increased blood PCB levels. Given the lack of support for an association between PCBs exposure and non-ASHD circulatory system deaths from * previously reported mortality studies, and the inconclusive relation between cardiovascular risk factors and blood PCBs, th is excess cause of death mist be viewed as a preliminary finding, in need of support from other studies. While previous mortality studies as well as toxicological studies have implicated a variety of cancers - digestive system, l i v e r , pancreas, malignant melanoma - as possible results of exposure to PCBs, the present study provides no support to such findings. In the Monsanto worker cohort, no deaths were a ttrib u te d to li v e r or pancreatic cancer, nor were any malignant melanomas found. The overall excess in cancer deaths, while not s t a t i s t i c a l l y s i g n i f i cant {8 observed, 4.46 expected, SMR =' 179), is mainly a r e s u lt of respiratory cancer deaths in workers for whom smoking habits were not ascertained. Although the present study's results do not support a carcinogenic e f fect associated with PCB exposure, there are s ig n ific an t lim itations to the r e s u lt s A principal limitation is the size of the worker cohort, which prevents the detection of increases in risk to deaths from rare diseases. A much la rg e r cohort followed for a longer period would be necessary to detect a two-fold increase, for exampTe, in observed li v e r cancer deaths. In order to allow for a latency period, the study cohort was limited to those working a t l e a s t six months until December, 1965. Since PCB production continued until 1977, further follow-up of the mortality of Monsanto's PCB-exposed workers will have larger numbers, as well as longer follow-up time. Another lim itation common to retrospective studies of occupational cohorts is. lack of knowledge of exposures from other work-related a c t i v i t i e s . While personal habits, such as smoking and drinking, can sometimes be roughly ascer tained i f co-workers or family members are available for interview, previous *> J u d i t h A. Zack/Page 10 exposures, or concurrent occupational exposures during follow-up, are often' impossible to-assess. The connection of an e f f e c t to a previous PCB exposure must f i r s t consider other potential effect-rela ted exposures. A useful comparison group in occupational mortality studies is an unex posed industrial cohort, from the same plant, i f possible. Ascertainment of mortality of such a cohort allows for conparison of SMRs between exposed and unexposed cohorts, which reduces the possibility th a t an elevated cause of death in the exposed cohort is a resu lt of a generally greater than expected cause-specific mortality in th a t area or industry. Such a comparison group would have been useful in evaluating the elevated mortality due to non-ASHD circulatory system diseases found in this study. Given the size of the study cohort and the other lim itations described above, the r e s u lts of th is analysis of PCB-exposed workers' mortality experi ence are not definitive, but rather contribute to the health-effects research on PCBs. A future study of th is cohort could evaluate., the mortality, of workers involved from the i n i t i a l through the final year of PCB production, and thus have more power to detect any possible hazards of PCB exposure.  . \ - '* J u d i t h A. Zack/Page 11 References 1. Meigs, J.W., Albom, J . J * , Kartin, B.L. Chloracne from an unusual expo sure to Arochlor. J.A.M.A. 154:1417-1418, 1954. 2. Kuratsune, M., Yoshimura, T., Matsuzaka, J . , Yamaguchi, A. Epidemiology study on Yusho, a poisoning caused by ingestion of rice oil contaminated with a commercial brand of polychlorinated biphenyls. Environ. Health Persp. 1:119-128, 1972. 3. Chang, K .J., Cheng, J .S . Huang, P.C., Tung, T.C. Study of patients with PCS poisoning. J. Formosan Med. Assoc. 79:304-313, 1980. 4. Urabe, H., Koda, H., Asahi, M. Present s ta te of Yusho patients. Ann. N.Y. Acad. Sci. 320:273-276, 1979. 5. Nagayama, J . , Kuratsune, M., Masuda, Y. Determination of chlorinated dibenzofurans in Kanechlors and "Yusho o i l . " Bull. Environ. Contain. Toxicol. 15:9-13, 1976. 6. Kamps, L.R., Trotter, W.J., Young, S .J ., Carson, L .J ., Roach, J.A.G., Sphon, O.A., Tanner, J . T . , McMahon, B. Polychlorinated quaterphenyls identified in rice oil associated with Japanese "Yusho" poisoning. Bull. Environ. Contain. Toxicol. 20:589-591, 1978. 7. Kashimoto, T . , Miyata, H., Kunita, N. The presence of polychlorinated quaterphenyls in the tissues of Yusho victims. Food Cosmetics Toxicol. 19:335-340, 1981. 8. Kashimoto, T . , Miyata, H., Kunita, S . , Tung, T.C., Hsu, S .T ., Chang, K.J., [ Tang, S.Y., Ohi, G, Nakagawa, J . , Yamamoto, S. Role of polychlorinated dibenzofuran in Yusho (PCB poisoning). Arch. Environ. Health 36:3211 326, 1981. ft J u d i t h A. Zack/Page 1*2 i 9. Kimbrough, R.D., Linder, R.E., Gaines, T.B. Morphological changes in live rs of rats fed polychlorinated biphenyls. Arch. Environ. Health 25:354-364, 1972. 10. Kimbrough, R.D., Squire, R.A., Linder, R.E., Strandberg, J .D ., Montali, R .J., Burse, V.W. Induction of liv e r tunors in Sierman s tr a in female r a ts by polychlorinated biphenyl Arochlor 1260. 0. National Cancer Inst. 55:1453-1459, 1975. 11. Quw, H.K., Simpson, G.R., Siyali, D.S. Use and health effects of Arochlor f 1242, a polychlorinated biphenyl, in an electric al industry. Arch. Environ. Health 31:189-194, 1976. 12. Maroni, M., Colombi, A., Cantoni, S., F erioli, E., Foa, V. Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environ mental and blood polychlorinated biphenyls concentrations. B rit. J . I Industr. Med.'38:49-54, 1981. 13. Chase, K.H., Wong, 0., Thomas, D., Berney, B.W., Simon, R.K. Clinical and metabolic abnormalities associated with occupational exposure to polychlor inated biphenyls (PCBs). J. Cccup. Med. 24:109-114, 1982. 14. Fischbein, A., Wolff, M.S., L ilts, R., Thornton, J . , Selikoff, I . J . Clin ical findings among PCB-exposed capacitor manufacturing workers. Ann. i N.Y. Acad. Sci. 320:703-715, 1979. 15. Marcni, M., Colombi, A., Arbosti, G., Cantoni, 5 ., Foa, V. Occupational exposure to polychlorinated biphenyls in e le ctric al workers. II, Health e f f e c t s . B rit. J. Industr. Med. 38:55-60, 1981. 16. Baker, E .L ., J r . , Landrigan, P .J ., Glueck, C.L., Zack, M.M., J r . , Liddle, J .A ., Burse, V.W. Houseworth, W.J., Needham, L.L. Metabolic consequences of exposure to polychlorinated biphenyls (PCB) in sewage sludge. Am. J. Epidemiol. 112:553-563, 1980. \ J u d i t h A. lack/Page 13 17. Bahn, A.K., Rosenwaike, I . , Herrmann, N., Grover, P., Stellman, J-, O'Leary, K. Melanoma a f te r exposure to PCBs. N. Engl. J- Med. 295:450, 1976. * 18- Lawrence, C. PCB? and melanoma. N. Engl. J. Med. 296:108, 1977. 19. Brown, D.P., Jones, M. Mortality and industrial hygiene study of workers exposed to polychlorinated biphenyls- Arch. Environ. Health 36:120-129, 1981. 20. Bertazzi, P.A., Zocchetti, C., Guercilena, S-, Foglia, M.D., Pesatori, A. , Riboldi, L. Mortality study of male and female workers exposed to PCBs. Int. Symposium on Prev. of Occup. Cancer, Helsinki, Finland, April, 1981. 21. Eighth Revision, International Classification of Diseases, Adapted for Use in the United States. U.S. Department of Health, Education, and Welfare, Public Health Service, PHS Pub!ication Ho- 1693. Washington: U.S- Govern ment Printing Office, 1977. 22. Monson, R.R. Analysis of relative survival and proportional mortality. Comput. Biomed. Res- 7:325-332, 1974. 23. Bailar, J .C ., Ederer, F. Significance factors for the ratio of a Poisson variable to i t s expectation. Biometrics 20:639-643, 1964. 24. Kreiss, K., Zack, M.M., Kimbrough, R.D., Needham, L.L., Smrek, A.L., Jones, B. T. Association of blood pressure and polychlorinated biphenyl le v e ls. J.A.M.A. 245:2505-2509, 1981. 25. Bumgarner, J . E . , Hammer, D .I., Colucci, A.V., Creason, J . P . , Finklea, J .F . Polychlorinated biphenyl residues in refuse workers. Research Triangle Park, Worth Carolina, National I n s t i t u t e of Environmental Health and Safety, Public Health Service, Department of Health, Education, and Wel fare, 10 p p ., 1973. ; Judith A. Zack/Page 14 V; Table 1 Follow-up Status of Polychlorinated Biphenyl Workers as of December 31, 1977 Follow-up Status Number Status known 88 Verified alive 58 Verified deceased 30 Death c e r t i f i c a t e found 30 Death c e r t if i c a t e net found 0 Status Unknown 1 Total 89 \ J u d i t h Ai Zack/Page 15 Table 2 Person-years of Observation Contributed by Polychlorinated Biphenyl Workers by Age Age in Years Person-years of Observation 20-24 11.4 25-29 63.8 30-34 142.6 35-39 222.5 40-44 283.2 45-49 325.3 50-54 294.5 55-59 207.6 60-64 134.0 65+ 115.2 'Total 1800.1 J u d i t h A. Zack/Page 16 Table 3 Duration of Exposure to Polychlorinated Biphenyls by Vital Status Years of Exposure* Livi ng (n = 58) Vital Status Deceased (N = 30) Unknown (n = 1) <1 20 5 1 1-3 20 12 0 3-5 6 4 0 >5 12 9 0 Total (n = 89) 26 -32 10. 21 Average Length of Exposure 3.2 yrs. 3.7 yrs. 0.7 y r s . 3.3 y rs. Lifetime exposure prior to 1-1-66 J u d i t h A. Zack/Page 17 Table 4 I.C.D, No, (Eighth Rev.) 140-209 140-149 150-159 155, 156 150-154, 157-159 160-1G3 162, 163 160, 161 185-189'200-209 164-184, 190-199 Observed and Expected Deaths Due to Malignant Neoplasms by Race, PCB Worker Cohort . Cause of Death White Males 0 E SMR* Nonwhite Males 0 E SMR* All Malignant neoplasms 4 2.70 148 4 1.76 227 Buccal cavity & pharynx 0 0.09 - 0 0.07 - Digestive organs & peritoneum 0 0.75 - 1 0.58 172 Liver 0 0.05 ' - 0 0.05 - Other digestive organs 0 0.70 - 1 0.53 189 Respiratory system 3 0.94 319 1 0.59 169 Lung 3 0.89 337 1 0.55 182 Other respiratory organs 0 0.05 - 0 0.04 - Genitourinary organs 0 0,28 - 1 0.23 435 Lymphatic & hematopoietic t i ssue 0 0.28 - 1 0.12 833 All other sites 1 0.36 278 ' 0 0.17 - *No SMR was s t a t i s t i c a l l y significant (all p-values greater than 0,05) Total 0 E SMR* 8 4.46 179 0 0.16' - 1 1.33 0 0,10 1 1.23 4 1.53 4 1.44 0 0,09 1 0.5V 75 81 261 278 - 196 1 0.40 250 1 0.53 109 J Uu wil A* uu Ck/i u Race Nonwhite Nonwhite Nonwhite White White White Nonwhite White Year of B1 r t h 1909 1913 1909 1893 1912 1916 1907 1906 Table 5 Case Summaries of Cancer Deaths Among Polychlorinated Biphenyl Workers Year of F1 r s t Exposure Year of PCB Exposure Death ' Duration (mo.) 1942 1959 13 1954 1965 85 1951 196B 1943 1963 1951 1968 1951 1977 1945 1964 1940 1957 28 34 28 33 8 79 Death C ertificate Cause of Death (ICDj?) Carcinoma of colon (153.8) Carci nomat osi s Priniary s i t e , kidney (189.0) Carcinoma of lung (162.1) Carcinoma of right lung (162.1) Carcinoma of lung (162.1) Carcinoma of lung (162,1) Multiple myeloma (203.0) Metastatic carcinomacarcinomatosis (199.0) J u d i t h A. Zack/Page 1-9 Table 6 I.C.D. No, (Eighth Rev.) 390-458 410-413 390-409, 414-458 460-519 520-577 800-998 - Observed and Expected Deaths Due to Non-malIgnant Causes by Race, PCB; Vtorker Cohort Cause of Death White Males . 0 E SMR Nonwhite Males 0 E SMR Diseases of the circ u la tory system 11 6.82 161 5 4.35 115 Arteriosclerotic heart di sease 4 4.99 80 3 2.20 136 All other circulatory system 7 1.83* 526* 2 2.15 93 Diseases of the r e sp ir a tory system 0 0.73 - 1 0,54 185 Diseases of the digestive system 1 0.75 133 1 0.45 222 External causes of death 0 1.43 - 1 0.95 105 All other non-malignant . causes 2 1.10 182 0 1.30 - Total 0 E SMR 16 11.17. 143 7 7.19 97 9 3.98 226* . 1 1.27 79 2 1.20 167 1 2.38 42 2 2.40 83 Total All causes, malignant & non-malignant 18 13.53 133 12 9.35 128 30 22.88 131 *p < 0.05