Document eE3N8N0vBpdJM3nV8358mXr4

1\ k-% Journal of Occupational Medicine ISSS .!*. t " In Editor LLOTD 8 TEPPER MO Asiocute Editor ROBERT R HILKER M D Executive Editor DORIS L FLOlRnOV m S Editorial Bojrd H DEAN BELK M 0 PATRICIA y "ACENDORN MO HENRY R HERBERT M 0 I AMES P HUCHES MD BRUCE W KARRH, M D PAUL KOTIN, ,M D THOMAS A LINCOLN, M D BRIAN MacMAHON, M D IAMES W MITCHELL. MD OAVID B ROBBINS, M D Production Manager LUCILLE ROBERTS Manuieript Coordinator BARBARA VASUMPAUR Circulation Manager NANCY OLSON The journal of Occupational Medicine is owned, copyrighted, and published monthly by the American Occupational Medical Association ISO North Wacker Dr, Chicago, IL 60006 Second class postage paid at Chicago, IL Title registered. United States Patent Office Subscriptions S25 00 per year, U S S30 per year, Canada and elsewhere Single copies 13 50 Allow four weeks for first issue Publisher cannot assume respon sibility for replacing undelnered issues, Pr issues damaged m transit unless notified not later than the end of the second month following the month of issue Although all advertising material ac cepted is intended to conrorm to ethical medical standards, acceptance does not imply endorsement by the journal Change of Address Nonces should in elude old address as well as new Attach label from recent issue it available Be sure to include Tip codes tor both old and new address Allow four weeks for change to become effective Manuscripts submitted for publication should be sent to Doris floumov. Ex ecutive Editor, fournal of Occupational Medicine. 150 N Wacker Drive. Chicago. IL 60606 ADVERTISING REPRESENTATION CHARLES B SLACK, INC Thorofare, N| 08086 (609i 848-TOOO Marketing Director RICHARD N ROASH Advertising Sales Representative SUSAN CROWLEY POSTMASTER: Please send Form 3579 to lournal of Oc cupational Medicine, 150 N. Wacker Drive, Chicago. II 60606 July, 1981 Vol. 23 No. 7 ORIGINAL articles Fluoride Balances in Pregnant and Nonpregnanl Women U R Maheshwari, B D S . Ph D , et a I Developing Job-Related Preplacement Medical Examinations Joyce C Hogan, PhD, and Edward I Bemacki. MO. MPH Editorial Response A Component Analysis of an Alcohol and Drug Program: Employee Education B H McLatchie, PhD. P M Grey, MA.Y lohns. MA, and K C E Lomp, M A Shooting, Sensorineural Hearing Loss, and Workers' Compensation David Y Chung, Ph D.. R Patrick Cannon, M.D.; Clenn N Willson, M.D, and Keith Mason, MS A Retrospective Cohort Study of Mortality and Cancer Incidence Among Chemists Shelia K Hoar, Sc.D., and Sidney Pell, Ph D A Retrospective Cohort Study of DisabilityAmong Chemists Shelia K Hoar, Sc.D, and Sidney Pell. PhD Health Concerns in Uranium Mining and Milling Victor E. Archer, M.D 465 469 475 477 481 485 495 502 DEPARTMENTS Letters-to - the- di tor Defusing the Time Bomb Book Reviews Forensic Toxicology Therapeutic Activities for the Handicapped Elderly 1980 Year Book of Family Practice Health and Safety Aspects of Mining -- A Bibliography Mental Wellness Programs for Employees The Handbook of Placement Assessment Resources Early Rehabilitation at the Work Place The Chemical Elements and Man 453 456 456 456 456 457 457 457 458 OM Forum Selected Reviews from the Literature 460 506 Association Affairs Annual Meeting Report General People and Events Classified Advertising (Classified Ads also appear as display advertising See Advertisers Indev > Advertisers' Index 510 515 516 520 MANUSCRIPTS Contributors are terjuested to read Jnrormatfon tor Authors which is ptohyhed m the January May and September unu** ot the lournal and which mas be obtained from the Editorial Office upon request failure to follow the guidance contained therein ^.tv cause delay m the consideration of manuscripts tor publication OLI 6743 I A Retrospective Cohort Study of Mortality and Cancer Incidence Among Chemists Shelia K. Hoar, Sc.D., and Sidney Pell, Ph.D. This retrospective cohort study examines mortality and cancer incidence among 3,656 men and 75 women who were employed as chemists in 1959. During the period 1964 to 1977, the male chemists experienced lower overall mortality than other salaried employees of the chemical company (198 deaths observed, 241.0 expected, SMR = 82). Large deficits are seen in lung cancer and arterioscle rotic heart disease deaths. The chemists appear to be at slightly higher risk for death from malignancies of the col on (12 observed, 6.7 expected, SMR -- 178)and from cere brovascular disease (IS observed, 10.8 expected, SMR = 138). The low overall mortality resulted in a larger than ex pected proportion of deaths due to cancer. Fewer than ex pected cases were diagnosed of cancer of all sites com bined (61 observed, 86.5 expected, SIR = 71) and of the lung (8 observed, 200 expected, SIR = 40). The incidence rates of melanoma and of cancer of the prostate are slight ly higher than expected, relative to the Third National Cancer Survey and the experience of nonchemists, respec tively. Among female chemists, deaths due to all causes and suicide occurred more frequently than expected. Possible explanations tor the lack of anticipated excess risks and for the observed deficits are presented. Keports from the United States, Sweden, and Great Britain suggest there is excess mortality from certain types of cancer among chemists' " However, the designs of the studies reported have some limitations. First, the populations were not restricted to persons employed as chemists. The American and British studies of chemical society members may include persons who were not oc- from the Department o* Eptttefmologv Harvard School of Public Health, 677 Huntington Av# Boston ma 02115 (Dr Hoar) and Epidemiology Section I'tdicai Division C I du Pont <j* Semours and Co Inc Wilmington Dl 19898 iDr Pell. Addrf's comrr^Aications to Dr Hoar Environmental Epidemiology Branch Nation*) Cancer -sMutn Lando* IC06 Bethesda MD 20205 SupOCTted b\ giants no- t I du Pont de Nemours and Co Inc the E*on Corporation and the Lm'pd Nar>on*l Cancer institute (5 P01 06373* Journal ol Occuoationai Medicme/Vol. 23. No. 7/July 1981 cupationally exposed to chemicals, for example, admini strators for chemical companies,11 * Secondly, several of the studies were based on proportional mortality rates, not absolute mortality ratesApparent excesses in proportional mortality from cancer may reflect deficits in other causes of death.10 Thtadfv, the Swedish sttfdy which was based on absolute mortality and attempted to iden tify subjarti who wotted tr*a laboratory included too few deaths to bo conclusive.* E I. du Pont de Nemours and Company, Inc . employs many chemists and was concerned over these reports Du Pont had data available to identify many persons em ployed as chemists and to generate cancer incidence and mortality rates This paper describes an absolute mortali ty and cancer incidence study of chemists employed by that company. Materials and Methods The Du Pont Company maintains a computerized per sonnel file which includes records of all salaried persons who were active employees on or after lanuary 1, 1964 Records of hourly wage roll workers are not included in the file The file contains demographic information and work histories retroactive to 1959 From this file, the authors identified 3,713 men and 75 women who ysere employed in 1959 as chemists, chemical engineers or research associates, or in occupations with similar 10b titles. Because of the small number of nonwhites the cohort was restricted to 3,686 male and 75 female white chemists It is difficult to define the iob title "chemist" and to characterize occupational exposure Most chemists are exposed to numerous substances that change constantly in quantity and in quality Difterent chemists rarely >u'tain the same exposures. This is especially true tor a cohort of Du Pont chemists. Du Pont is an international company with many different processes, products and locations, and chemists are employed throughout the company A large number are employed in research and development at the Experimental Station m Wilmington OLI 6744 -- Table 1 - Du Pont Department Groups and Products Name P'astic resins iioers anc products Basic cnemicais ana finishes Examples ot Products or Exposures Plastic resins tiiamems. sneetings enpto grapnic oaoers, chemicals ana eauipment textile fiDers Pamls. pigments, enromates Iirnsnes te traethyl lead, tluormatea camDOunas eyes solvents polymers lor non-plastic uses ary ceanmg fluid soaium procucts eiect'omc products plant protection cnemicais 'eec supplements pnarmaceuticais Dasiccremrcais and intermediates Petrochemicals Acrylonitrile, explosives industrial diamonds Elastomers Neoprene accelerators, antioxioants and miscellaneous chemicals for natural ana synthetic rubber, coated fabrics Research oevrooment anc engineering Atomic energy Aarmnistration Low-level radiation Del, while others work in research and development at the plants Some are involved with pilot plants or semi works operations for new products and processes, and others serve in engineering or quality control positions at the production plants This variety is further complicated bv rotation of some chemists from plant to plant orto the Experimental Station The same job title and code number can represent dif ferent tasks at different company locations. For instance, "technical investigator" could be a laboratory research position at one location, but an administrative position at another A chemical engineer could do laboratory work at one site, but design work on a computer at another. A few tasks are consistent across locations. For example, a "pat ent chemist" is always an office job, but the position may be held by someone who was once a laboratory research chemist. Du Pont is organized into industrial and administrative departments. Within a department, the types of processes and products have some similarity. Because most employees stay within the same department throughout their careers despite transfers to several locations, ex posures were characterized by usual and "ever" depart ment affiliation. A Du Pont industrial hygienist identified the seven major department groups that existed during the study years, combining those that had undergone name changes and reorganization (Table 1)." The authors also identified 19,262 male and 673 female white "nonchemists" who were active salaried employees in 1959 and were listed in the computerized personnel file on January 1.1964 Persons ever employed by Du Pont as chemists were excluded from the nonchemist group Extracts of the personnel records were created and missing demographic data were obtained from noncom puterized employee rosters stored by the Du Pont Epidemiologs Section- Cancer Incidence -- Cancer cases were ascertained bv review ot the Medical Division cancer registry The registry consists of cases gleaned from the Accident and Health Insurance (AHI) claims and life insurance claims The AHI claims are submitted for any disability of eight or more consecutive days The diagnosis on the disability claim is certified by the attending physician About 97% of employees with at least Six months of service are enrolled in the AHI plan and all employees are enrolled in the life insurance plan The registry and insurance plan have been described in detail in other studies 11 Cancer incidence data are available only during the sublets' years of active employment at Du Pont Ill nesses that occur after termination from the Company, or during retirement, are not recorded in the registry Using a computer program developed by Monson," the observed number of cancer cases diagnosed during the period 1964 to 1977 was compared with the estimated expected number based on the experience of the non chemists and on the Third National Cancer Survey (TNCS) rates '* Standardized incidence ratios (SIRs), the ratios of the incidence rates of the chemists and the comparison group, standardized to the age and calendar year distribu tion of the person-years of the chemists, were calculated. Ninety-five percent confidence intervals were con structed, assuming a Poisson distribution of the observed number of events.1' The TNCS rates were used to detect excess risks occur ring in both the chemist and the nonchemist cohorts which would not be apparent from internal comparisons. A third comparison group, all Du Pont salaried employees from each year of the study observation period, was considered. The more inclusive Du Pont salaried group was larger than the nonchemist group, but less comparable to the chemists with respect to year hired and socioeconomic status. The results based on all Du Pont salaried employees were similar to the nonchemistbased analysis and will not be presented. For all sites combined and for any site with three or more chemist cases, the authors examined the effects of age and decade hired, and usual and ever department af filiation. For each value of the factors, the expected number of cases was generated by consideration of the nonchemists with the same value for the factor The effects of alcoholism were also examined. A sub ject was classified as an alcoholic if he had a cause of death or disability due to alcoholic cirrhosis of the liver or to alcoholic psychoses, or had been identified in a company-wide survey of plant physicians conducted in 1964 " An AHI claim for alcoholism can be filed for an episode of illness or for a 30-day treatment course at an alcoholism rehabilitation center Referral to a rehabilita tion center may be made by either the employee or by management. Mortality -- The chemist and nonchemist cohorts were followed to December 31, 1977, regardless of employment status. The mortality data were obtained from two sources, Du Pont records and the Social Securi ty Administration (SSA). The Medical Division maintains a mortality file which records all deaths among active employees and among pensioners The file contains the life insurance claim data, supplemented by information 486 Mortality and Cancer Incidence Among Chemists/Hoar and Pen OLI 6745 Table 2. -- Vital Status, as of December. 1977. ot the Chemists and Nonchemist Cohorts, by Sex Vital Status Tota Alive Ac' .e erne :ees Pe's,oners Te'-vnatec f-om company *:' oc*: "sc Deceased A:* .e em; c.ees Pe*s.oners Te'minale: `-om company, net Densoned Percent ot total for tne sex-cohort group tless man iv: Chemists Men Women 3 636 3 488(95)* 2.722(741 448(12) 75 69(92) 41(55) 13(17) 318(9) 198(5) Ilti3i 76121 15.20) 6<8i 4(5) 1(11 11 + id) Nonchemists Men Women 19,263 1 7 243(90) 10 867(561 5,465(28) 673 , 653(97. 454(67) 1 70(25. 9n(5) 2 020(10) 897(5) i 071(61 29(4, 20(3, 9(1, 10(1) 52t It from the employees' medical records and from the plant physicians. As of December 31, 1977, 187 male and 5 female chemists and 1,979 male and 19 female non chemists were known to have died while actively employed or after having retired. Of the 329 male' chemists who left the company before retirement or death, the SSA identified 260 as alive, 11 as deceased, and 58 as status unknown. Persons not known to be dead were assumed to be alive until the end of the study. One female chemist and one female and 51 male nonchemists were known to have died after termination from Du Pont (Table 2). The authors requested copies of death certificates from state departments of health, but did not try to ob tain certificates for 11 nonchemists and one chemist who died outside the United States Certificates were obtained for 185 (93%) of the male and 6 (100%) of the female deceased chemists and for 1,863 (92%) of the male and 15 (79%) of the female deceased nonchemists. When a certificate was unobtainable, the cause of death from the life insurance claim was utilized. Ninety percent of the available certificates contained the same cause of death as the life insurance claim. Ninety-rune percent of the deaths attributed to cancer on the death certificate were also attributed to cancer on the life insurance claim. Cause of death was coded according to the Interna tional Classification of Diseases, Adapted for Use in the United States.w " The Seventh Revision was used from Table 3. - Observed and Expected Cancer Cases* Among Male Chemists. Aged 20-64. Diagnosed in 1964-1977, Based on the Nonchemist Cohort Rates. Site (ICDIT An sues 114C-239] Buccai cav.t, (140-1A9i Stomacn 115' Small ano (a_.niestme 1152-153) Rectum (154 l.ver ano D, ;-y passages (155-156) Pancreas lie') Lung (162) Melanoma f72) P-ostaie (183 Biaooer (188 K.dney (189 , Brain 11911 Endocrine g sics excluding thyroid (194) Lvmonatic a*d nematoooieiic system (200-209) lymohosa-coma .2001 Hodgkin s c-sease ,20i) Other 'ymc-jmas 12021 MuWDie m .eioma i203) Leukemia 204-237 Other nec: -sms o' lym- DhODOie' : system i208l*209tf am other sue; Obs 61 1 2 7 3 1 2 8 8 7 3 4 2 1 12 3 2 1 1 3 2 0 'ExciuOmg -:n-me a*:'.c skin cancer tEigmn Rev = on -.:e-aiionai Classification ot Diseases'6 tStanoaroite: >nc ;e":e 'alio (SIR) lopserveo/expecieci ICC 695% coniici-ce --e-va s1kPoiycytne- tfi v. aaenogemc myeio.o metaplasia Journal of OccuDfonai Medicme/Vol. 23. No 7/July 1981 Exp 86 5 21 24 ii 6 44 09 11 20 0 83 45 20 37 30 05 10 0 2i i6 15 09 35 04 12 0 SIR! C 1 Ot SIR 71 54-91 48 2-235 83 14-275 60 26-119 68 17-IBS -- 181 30-598 40 19-76 97 45-184 156 68-308 150 38 407 108 34-261 67 11-221 120 65-203 142 36-385 127 21-419 67 3-332 ---- 85 22-231 _-- OLI 6746 467 1 4j - i > i ! Ii i Table 4. -- Observes and Expected Cancer Cases* Among Male Chemists. Aged 20-64 Years. Diagnosed in 1964 1977. Based on the Third National Cancer Survey. 1969-1971. Site Aii sites Sytcai cavity Stomacf Sma*i and large intestine Rectum Liver and Binary DaSsages Pancreas Ljng Veianoma P'ostate B.aoaer kidney - Rrain.- Enoocnne glands excluding thyroid Lymphosarcoma Hocgkm s disease Other lymphomas Multiple myeioma LeuKemia All otner sites Oos 61 1 L * 3 2 8 6 7 3 4 2 1 3 2 1 1 3 2 'Excluding non-meianotic skin cancer ' iStandardizeo incidence ratio (SIR) * (observed/exoected) x 100 t95H confidence intervals'5 Exp 112 0 85 38 g9 57 16 37 28 4 33 55 66 38 34 03 27 21 10 1.2 33 17 1 SIR' C l of SIR: 54 42-70 12 ' 1-58 53 9-175 71 31-140 53 14-145 62 3-306 54 9-178 28 13-54 239 111-454 124 54-246 45 12-123 105 33-253 59 10-196 --Ill 28-303 97 16-322 97 5-479 81 4-397 91 23-249 -- Table 5. -- Observed and Expected Numbers of Deaths Due to Selected Ceuses Among Mile Chemists, 1964-1977, eased on the Nonchemist Cohort. Cause (ICO)* aii causes Malignant neoplasms (140-209) Stomach |151) Large intestine (153) Rectum (15*) Liver and Binary passages 1155-1561 Pancreas 1157) Lung |162l Prostate (i85) Bladder (188) Kidney |i89) Thyroid (193) Lynonatic ana nematopoieiic cancer (200-209) Lymonosarcoma and reticuiosarcoma (ZOO) Hodgkin s disease (201) Leukemia (204-207) Other lymphatic cancer (208-209) Diadetes meilitus (250) Circulatory system diseases (390-458) Arteriosclerotic heart disease (410-414) CereDrovascular disease (430-438) Pneumonia (480-486) Gastric and cuooenal ulcer (531-533) Cirrnosis ot the liver (571) Accidents (E800-E949) Suicide (E950-E959) Residual Obs 198 43 2 12 2 1 2 9 2 0 2 1 1 9 1 2 4 2 1 95 75 15 3 1 5 14 8 27 -Eighth Revision international Classification of Diseases'* TStanaardized mortality ratio - looserved/expected) x 100 t95r. conliaence intervals'- 488 Exp 241 0 62 4 22 67 0.9 17 17 21 9 2.8 1.1 2.3 30 0.2 75 12 07 3,7 20 32 128 1 103.3 10 8 11 06 57 13.5 5.6 20.8 SMRt 82 69 90 178 - 59 120 41 72 -- 86 33 -- 120 85 -- 109 102 32 75 73 138 281 -- 88 104 144 -- C.l. Of SMRJ 71-94 51-92 15-300 97-305 - 3-290 20-389 20-75 12-236 -- 15-287 2-164 -- 59-220 4-411 -- 34-261 17-337 2*154 61-92 57-91 81-224 69-742 -- 32-194 59-170 66-271 Mortality and Cancer incidence Among Chemists/Hoar anc OLI 6747 1964 throjyh A.nd the E lyhth Revision, trom 1%9 through 197" Through the use of the Monson program, the observed number of deaths among the chemists was compared with the estimated expected number based on the ex perience of the nonchemists and on the U S mortality rates Standardized mortality ratios (SMRs) and 95% con fidence intervals were calculated m the manner described previously An analvsis based on all Du Pont salaried personnel employed during the study observation period yielded results similar to those of the nonchemist-based analysis and will not be presented Proportional mortality ratios (PMRs) also were calcu lated, comparing the mortality patterns of the chemists with those of w hite male population of the United States. Results Cancer Incidence. -- While employed as chemists at Du Pont, the 3,686 men accrued 44,656.8 person-years of observation With the exclusion of non-melanotic skin cancer, 61 cases of cancer were diagnosed during the period 1964 to 1977 The expected numbers of cancer df all sites were 86 5 (SIR = 71) and 112.0 (SIR = 54), based on the nonchemist and the TNCS rates, respectively. Table 3 shows the observed and the expected numbers, the SIRs, and the 95% confidence intervals of the SIRs, based on the nonchemist experience, for all combined and for selected cancer sites. Approximately one-half of the deficit in overall cancer morbidity was attributable to the low lung cancer morbidity Slight excesses, based on small numbers, were seen for cancers of the pancreas, the prostate, the urinary bladder, and the lymphatic and hematopoietic system A slight excess of prostatic cancer is seen among chemists ever and usually employed in basic chemicals and finishes (3 observed. 1 0 expected). All the chemists diagnosed with kidney cancer were employed in basic chemicals and finishes (ever- 4 observed, 0.6 expected; usual: 4 observed, 0 4 expected). Slight excesses were seen in the plastic resins and fibers chemists for lymphosar coma (ever 2 observed, 0.3 expected; usual; 2 observed, 0 2 expected) and leukemia (ever. 3 observed, 1.1 ex pected, usual 2 observed, 0,4 expected). The number of cases is too small for multiple breakdowns to be meaning ful The comparison of the chemists with the TNCS popula tion was generally consistent with the nonchemist-based analysis (Table 4). However, melanoma was more com mon among the chemists than expected (8 cases ob served, 3.3 expected, SIR = 239), an association that does not appear in the nonchemist-based analysis. An excess of melanoma is observed in the nonchemists themselves in comparison with the TNCS population (38 cases ob served, 171 cases expected, SIR = 223). In the internal comparison with the nonchemists, the chemists do not appear to have excess melanoma risk. The female chemists accrued 747,0 person-years of observation During the period 1964 to 1977, five cancers were diagnosed one each of the breast, uterus, and ovary, one case of leukemia, and one cancer of unknown primary site. The expected number of cancers of all sites Jouraai of Occupational Medicine/Vol. 23. No. 7/July 1981 Table 6. -- Observed and Expected Numcer ol Deaths Due to Cancer of the Large intestine Among Mate Chemists. 1964-1977, by Work History Characteristics. Based on the Nonchemist Cohort. Age mred JO-2* 25-29 30-34 35-44 Decaoe hirec 1920-1929 1930-1939 1940-1949 1950-1959 Usual department group Plastic resms and fiDers Basic chemicals ana finishes Petrochemicals Elastomers Research, development ana engineering Atomic energy Total Obs 3 4 4 * 0 4 4 4 3 4 2 0 2 1 12 Exp 2' 32 oe 04 11 23 t2 2t 34 20 03 02 05 00 67 was 2.7 (SIR = 185), based on both the nonchemist and the TNCS rates. Because of the small number of cases, no further analysis of the women's experience will be presented. Mortality. -- From 1964 to the earlier of either the date of death or the end of the study, the male chemists ac crued 50,538.7 person-years of observation and 198 deaths. The expected numbers of deaths were 241 0 (SMR -- 82) and 418,3 (SMR = 47), on the basis of the ex perience of the male nonchemists and of the U S white male population, respectively. In comparison with the experience of the nonchemists, deaths due to malignant neoplasia were less frequent than expected (43 observed, 62.4 expected, SMR = 69) (Table 5). An elevated SMR was seen for cancer of the large intestine (12 observed, 6.7 expected, SMR = 178) A large deficit was observed for deaths due to carcinoma of the lung. Nine lung cancer deaths occurred, 21 9 were ex pected (SMR = 41) Slight excesses were observed for deaths due to Hodgkin's disease, to all lymphatic and hematopoietic cancer, and to cerebrovascular disease, pneumonia, and suicide. A low SMR was seen for arteriosclerotic heart disease. Table 6 presents the observed and expected numbers for cancer of the large intestine according to work history characteristics. Deaths occurred among chemists usually employed in plastic resins and fibers, basic chemicals and finishes, petrochemicals, research and engineering, and atomic energy The associations seen in the total cohort were generally found in each department. Chemists usually employed m the elastomers department experienced slightly more deaths than expected (13 observed, 11.8 expected. SmR = 110); chemists in the other departments had SMRs well below 100. The elastomers department's relative excess was due to deaths from coronary heart disease and suicide. However, for most departments and most causes of death, the number of deaths was too small for any meaningful comparisons 489 OLI 6748 Table 7. -- Observed and Expected Numbers of Deaths Due to Selected Causes Among Male Chemists. 1964-1977, Based on u.S. Mortality Rates. Cause ah causes Malignant neooiasms Stomacn Large intestine Rectum Liver and biliary passages Pancreas Lung Prostate Bladder Kidney Brain Thyroid Lymphatic and hematopoietic system Lymphosarcoma and reticulosarcoma Hodgkin s disease Leukemia Other lymphatic cancer Diabetes meiiitus Diseases ot nervous system and sensory organs Diseases ot tne circulatory system Arteriosclerotic heart disease Cerebrovascular disease Respiratory piseases Pneumonia Digestive system diseases Gastric and duodenal ulcer Cirrhosis ot the liver External causes Accidents Suicide Residual Obs : 96 43 2 12 2 1 2 9 2 0 2 t 9 1 2 4 2 1 2 96 75 15 7 3 11 1 5 22 14 8 16 Exp 418 3 B6 0 36 69 24 13 47 30 7 28 19 24 Oi 02 91 22 1.3 34 2,1 5.8 3.9 198.9 151.5 20.0 20 9 7.3 26 5 2.5 17,1 54 2 34 7 13.6 22.1 SMR* 47 50 55 174 85 78 43 29 _70 83 .il-- 99 46 150 119 94 17 51 48 50 75 33 41 41 40 29 41 40 59 C 1 ol SMR* 41-54 37-560 9-184 94-296 t4-275 4-379 7-141 14-54 12---236 14-275 1-141 -- 48-182 2-224 26-508 37-284 16-315 1-85 9-169 39-59 39-62 44.-121 15-66 11-112 22-72 2-193 11-65 26-60 23-66 27-112 SMS . Standardize;] mortality ratio (oeserved/expected) * 100 T95% contidence intervals'* In comparison with the U S. white male general population, 86 0 deaths due to cancer were expected, yielding an SMR of 50 (Table 7). An excess was observed for deaths due to cancer of the large intestine (12 ob served. 6 9 expected. SMR = 174), Two Hodgkin's disease deaths occurred; 1 3 were expected (SMR = 150) Four leukemia deaths occurred; 3.4 were expected (SMR = 119) Deficits are seen in numbers of deaths due to car cinoma of the lung (9 observed, 30.7 expected, SMR = 29). arteriosclerotic heart disease, respiratory and digestive system diseases, accidents, and suicide. The deaths and person-years of exposure were categorized by employment status. Active employees had the lowest SMRs, pensioners had the highest, and ter minated, nonpensioned employees had intermediate SMRs The last group, the most difficult to trace, did not reveal any associations not seen in the active employees or the pensioner group Risk of cancer of the large intes tine was elevated relative to the overall SMR in both ac tive and pensioned employees, but particularly among the pensioners Only the active employees had slight ex cesses in deaths due to cancer of the kidney and to Hodg kin's disease Only the pensioners had excesses in deaths due to prostatic cancer, cerebrovascular disease, diseases of the digestive system, cirrhosis of the liver, and suicide (Table 8) 490 In the proportional mortality analysis, the method used in several of the previous chemist studies, deaths due to malignant neoplasia were found to be more frequent than expected (Table 9). A larger than expected proportion of deaths among active employees was due to lung cancer, but deficits were seen among the pensioned and other ter minated employees. Colon cancer, arteriosclerotic heart disease, and cerebrovascular disease were responsible for larger proportions of deaths than expected. Deaths at tributable to prostatic cancer occurred more frequently than expected among pensioners. The risk of deaths from accidents was lower than expected, and,'among ter minated employees, suicide accounted for a larger than expected proportion of deaths Among the female chemists, six deaths occurred during 994.7 person-years of observation. The expected numbers were 1 8 (SMR = 327) and 4.8 (SMR = 125), on the basis of the experience of the female nonchemists and of the U S white female population, respectively The causes of death were lung cancer, leukemia, abscess of the lung, house fire, and in two cases, suicide Compared to the U S. rates, only 0.1 deaths due to suicide were expected Discussion The Du Pont male chemists experienced lower overall mortality and lower cancer morbidity and mortality than Mortality and Cancer incidence Among Chemists/Hoar ana Pen OLI 6749 Table B. -- Observed and Expected Numbers ol Deaths Due to Selected Causes Among Male Chemists. 1964-1977. by Employment Status. Based on U.S. Mortality Rates. Cause ah causes Malignant neoplasms urge intestine Lung Prostate Kidney Lymonaiic ana nemaiODOietic cancer Hoagxm s aisease Circulatory system diseases Arteriosclerotic heart disease Cereorovascuiar disease Respiratory Greases Digestive system diseases Cirrhosis ot the liver Suicide Residual Actives Obs Exp in 309 7 25 61 8 5 4,7 7 22.0 0 1.2 2 18 6 70 2 12 49 141 0 40 108.7 5 12 6 2 13 5 7 21 6 3 14 4 4 11 9 24 59.9 *SMR - Standardized mortality ratio - (observed/expected) x 100 SMR* 36 40 106 32 -- HO 86 174 35 37 40 15 32 21 34 -- Pensioners Obs Exp SMR 76 91 5' 83 16 21 0 76 6 2 0 307 2 7 5 27 2 0 16 05 1--25 3 1 7 172 0 01 -- 42 50 7 83 31 37 2 83 9 68 133 5 6 8 74 4 36 111 2 2 18 09 114 -- 7 85 - expected on the basis of the experience of the industrial and general population comparison groups. Deaths due to cancer of the large intestine and to cerebrovascular disease occurred more frequently than expected. Small excesses of cases of prostatic cancer and of melanoma were observed. Sharply decreased rates of lung cancer in cidence and mortality and of arteriosclerotic heart disease mortality were observed. The female chemists ex perienced greater than expected mortality from all causes combined and from suicide. Among the men, the finding of excess mortality from cancer of the large intestine is based on 12 observed deaths, a number larger than that for any other cancer site Relative to the experience of the U.S. population, the excess of colon cancer was highest among pensioners. The deaths were distributed throughout all but two major Du Pont department groups. Larger than expected proportions of deaths due to cancer of the intestine and the rectum occurred among deceased ACS and British RIC members and among chemists dying in the state of California during the years 1959 to 1961* Among the Swedish chemistry graduates the number of deaths due to malignancies of the digestive system was approximately that which was ex pected.* A recent update of the Swedish cohort showed a slight deficit of digestive system cancer deaths." Among chemists dying in the state of Washington there was one death due to cancer of the large intestine; two deaths were expected.1 The incidence of cancer of the large intestine was not elevated with respect to the comparison groups. However, the incidence data are limited to active employees who are under age 65. If the excess frequency appears after age 64, as suggested by the U.S -based mor tality analysis, no excess in incidence would be expected. The Du Pont chemists show an excess of prostatic cancer relative to nonchemist salaried employees. The occurrence of prostatic cancer increases directly with age," so the Du Pont incidence data, restricted to cases diagnosed before the age of 65, may underestimate the Tabu 9. -- Obsarvad and Expected Numbers and Proportional Mortality Ratios for Deaths Due to Selected Causes Among Male Chemists, 1964-1977, by Employment Status, Based on U.S. Proportional Mortality Rates. Cause All causes Malignant neoplasms Large intestine Lung Prostate Kidney Lymphatic and hematopoietic cancer Hodgkin's Disease Leukemia Arteriosclerotic heart disease Cerebrovascular disease Respiratory diseases Digestive system diseases Cirrhosis ot the liver Accidents Suicide ActiveX Obi Exp PMR* ill 111 0 100 25 18 3 137 5 1.3 377 7 56 125 0 0.2 -- 2 0.5 -- 6 2 8 213 2 0.6 -- 3 1.1 284 40 29.8 134 5 3 a 132 2 3.9 51 7 8.2 85 3 5.6 54 12 19 2 62 4 7 1 56 PMR m Proportional mortality ratio - (observed/expected) x tOO journal of Occupational Medicine/Vol 23, No. 7/July 1981 Ptniloners Obi Exp PMR 76 76.0 100 16 179 89 6 1.5 398 2 6.9 29 2 08 -- 0 0.5 -- 3 1.5 196 0 0.1 -- 1 06 -- 31 30.4 102 9 4 1 221 5 4 6 109 4 4.0 1Q0 2 2.4 83 1 30 34 2 1.3 158 Total Obs Exp PMR 198 198.0 100 43 37 2 116 12 2.8 426 9 12.7 71 2 0.6 -- 2 1 1 187 9 4 7 192 2 0.9 -- 4 1.7 230 75 61.9 121 15 7,5 201 7 80 87 11 13 9 79 5 9 4 53 14 25 8 54 8 99 81 49i OLI 6750 Table 10 - Proportional Mortality Ratios and Estimated Standardized Mortality Ratios lor Selected Causes ol Death Among Male Chemists. Du Pont (Overall SMR - 47) Li et at1 < 65 Years Cause PMR,,,* SMR*,t PMR,,, SMR,,,! A i cancers 116 50 125 53 u3'ce intestine 426 174 115 54 Lung 71 29 116 54 Leukemia 230 119 132 62 Suicide Bi 59 117 55 Li et at' i.65 Years PMR,,, SMRtlt 115 54 134 63 80 38 178 84 100 47 Milium* Washington St. PMR,,, SMR,,, 99 47 43 20 63 30 213 100 195 92 Petersen tt at* California St. *M",o. SMR,,, 91 43 207 97 64 30 116 55 248 117 Registrar General' England and Wales PMR,t, SMR,,, 96 N/A 63 320 378 1 45 N/A 30 150 17B PMR.., - Cause soecilic oroporlionai morality ratio tSVR.,, = Cause-specific standardized mortality ratio tSMR^. * Cause-soecitic estimated standardized mortality ration* PMRm, x overall SMR (Irom Du Pont aata)22 n/A - Data not avauaoie w published report risk Both of the chemists who died from prostatic cancer that of the comparison group. Low overall mortality can were pensioners, again suggesting that the greatest risk is cause PMRs to overstate risk For deaths due to cancer, in the oldest age groups, for whom incidence data are the Du Pont male chemists had an SMR of 50 and a PMR unavailable The problem would be compounded if of 116, relative to the appropriate U S. comparison undetected cancer were associated with retirement or population. The earlier chemist populations with excess with employment termination. An excess of prostatic proportional cancer mortality also may have had low ab cancer is also seen among the Swedish chemistry ' solute cancer mortality. Table 10 presents the observed graduates and among the Californian chemists. PMRs and the estimated SMRs for selected causes of The incidence of melanoma was greater than expected death from the previous chemist cohorts and from the Du among the chemists and the nonchemists, based on the Pont chemists. The SMRs were estimated by multiplying experience of the TNCS population. A similar excess was each cause-specific PMR by the Du Pont overall SMR. seen among all Du Pont employees in the period 1956 to Few of the elevated PMRs are converted into elevated 1974 u A possible explanation may be occupational ex SMRs In each study, the observed or estimated SMR. for posure to chemicals, some of which are suspected of leukemia is greater than the SMR for deaths due to all causing non-melanotic skin cancer Another putative cancers. Conversely, the observed or estimated SMR for cause is exposure to solar radiation The maiority of Du lung cancer is smaller than the SMR for all cancers. The Pont plants are located in the southeastern United States Swedish absolute mortality study* showed greater cancer where exposure to the sun is high Fifteen southern states mortality than expected, inconsistent with the Du Pont have the highest mortality rates for melanoma, account results. ing for 37% of the melanoma deaths in the United Second, the follow-up period may be too short to per States" Sixty-five percent of the Du Pont salaried em mit detection of the anticipated excesses Slight excesses ployees are located in these same states of deaths due to lymphatic and hematopoietic malignan Excess deaths due to cerebrovascular disease were cies and of cases of bladder and of pancreatic cancer seen in the Du Pont chemist cohort and among chemists were seen, but the observed numbers of events rarely ex dying in the state of Washington during 1950 to 1971 1 ceeded the expected numbers by more than one Further Among the men and women, slightly more deaths than follow-up and reanalysis may yield enough cases to con expected were due to suicide. Reports from the ACS, from firm the earlier reports of increased risk of these diseases the states of Washington and California, and from the among chemists. Registrar General of England and Wales also mentioned The Du Pont subjects were hired as early as the 1920s, excess numbers of deaths due to suicide.1 * * ' An excess were actively employed in 1959, and were followed until of suicide among female physicians suggests that a December 31, 1977. The length of follow-up, 19 years, sociological phenomenon may account for the excess was thought to be adequate for investigation of lym among temale chemists.11 phatic and hematopoietic diseases; the average incuba Other excesses were anticipated on the basis of the tion period for leukemia associated with benzene ex previous studies of chemist populations. Almost all of the posure has been estimated at between 6 and 14 years." previous studies reported excess deaths due to all sites of The number of persons in the cohort was greater than in cancer combined and to lymphatic and hematopoietic the Swedish study, the other absolute mortality study of malignancies Several studies reported excesses in deaths chemists However, the chemists were younger and the due to bladder and pancreatic cancers. events fewer than estimated. Approximately three-fourths There are several possible reasons why the Du Pont ex of the chemists were active employees at the close of the perience was not consistent with the earlier reports of ex study. The numbers of cases and deaths are small cesses First the outcome measures differed: this study is Third, associations may have been obscured by expo based on cancer incidence and absolute mortality, while sure misclassification. The Du Pont cohort was restricted most of the earlier studies were based on proportional to persons employed as chemists who were thought to mortality Decoufld et al" 14 recently discussed the bias have had more exposures than either the previously of PMR analyses when the overall death rate differs from studied chemist cohorts or the nonchemists However, if 492 Mortality and Cancer Incidence Among Chemists/Hoar and Pell OLI 6751 onlv a 'mall suburuup ot the chemists s\ere exposed to hazardous substances, the excess fists would be diluted bv the larger unexposed group at low risk Also, some ot the Du Pont nonchemists sustained exposure to hazardous chemicals, contributing to the misclassitication problem Finally, the cancer incidence data afe limited to cases diagnosed before employment termination No cancers detected after age 65, the mandatory retirement age dur ing the observation period, are identified This restriction reduces the study's ability to detect excesses of disease increasing directly with age. Large deficits in overall mortality and in cancer mor bidity and mortality rates were observed among the chemists Deficits were anticipated in the comparisons with the U S general population because of the "healthy worker effect,"" but not in the comparisons with the Du Pont nonchemist group. Selection bias is an unlikely explanation for the defi cits The chemist and nonchemist subjects were selected in the same manner from preexistent records that were created without regard for future disease or death. Observation bias is also unlikely although incomplete ascertainment of deaths may have occurred. Deaths and cancer cases were identified through the Du Pont epidemiologic surveillance system which was established for all employees prior to the initiation of this cohort study. The 55A identified deaths among the employees who terminated employment prior to retirement Subjects were classified as dead, alive, or status unknown The sub jects not known to be dead were assumed to be alive un til the end of the study. If all the chemists whose status was unknown had been deceased, but all such non chemists were alive, the observed number of deaths would increase by 58 to 256. The expected number would decrease slightly because of fewer chemist person-years of observation, being at most 241 0, yielding an SMR of 106. It is unlikely that this extreme situation occurred. More than half of the chemists whose status was unknown and who had been last employed by Du Pont in the Delaware area had private or business phones listed in their names in the local 1978 phone books. The 5SA also may have erred in classifying as alive people who were deceased. In previous studies as many as 6% of persons known to be dead were classified as alive by the SSA." The most likely explanation for the deficits in the mor bidity and mortality expenence of the chemists is con founding. Factors associated with cancer may be distributed unequally between the chemist and the com parison groups. The significant deficit in lung cancer mor bidity and mortality among the chemists suggests smok ing habits different from those of the comparison groups. The chemists also had low mortality from cardiovascular disease and low incidence for several other cancers thought to be related to smoking: cancer of the buccal cavity, esophagus, stomach, and larynx." " The chemists had only one more case than expected of cancers of the bladder and of the pancreas, which also are associated with cigarette smoking. It was not possible to obtain smoking histories for past or present Du Pont chemists. Questionnaires and inter views could not be administered, and the smoking histories recorded in the annual medical examinations are unreliable However, some mtormation on smoking is known The Du Pont chemists are prohibited from smok ing in the research laboratories, while persons in many ot the nonchemist occupations, such as lawyers and accoun tants. have the freedom to smoke during the workday On-the-job smoking behavior may influence smoking habits outside of work Data on smoking and occupation from the National Center for Health Statistics 1970 Household Interview Survey showed that the smoking habits of chemists differed from those of other profes sional and technical workers and from those of other business management employees, such as accountants and auditors,0 Only 29% of chemists are current smokers, while 33% of accountants and auditors. 36% of professional, technical and kindred workers, and 37% of personnel and labor relations workers are current smokers. The percentage of smokers who smoked one pack or more per day was 59% for the chemists, 66% for professional, technical and kindred workers. 69% for ac countants and auditors, and 71 % for personnel and labor relations workers. A recent National Health Survey" stated that 41% of managers and administrators were current smokers while only 30% of professionals, such as chemists, presently smoked. The deficits observed in mortality from all causes, from all cancers, and from lung cancer are compatible with the differences in smoking habits reported in the surveys, but there may be other confounding factors also. For-exam ple, the chemists probably have a higher socioeconomic status than the comparison groups The nonchemists in clude persons, such as foremen, who began employment on the hourly wage roll. Summary In this study, Du Pont male employees with the job ti tle chemist or with associated titles experienced lower rates of overall mortality and of overall cancer morbidity and mortality than other salaried employees of the com pany. A large deficit is seen in lung cancer and arteriosclerotic heart disease The chemists appear to be at slightly higher risk of death from malignancies of the colon and from cerebrovascular disease The incidence rates of melanoma and of cancer of the prostate are slightly higher than expected, relative to the TNCS and the experience of nonchemists, respectively Among female chemists, deaths from all causes combined and from suicide occurred more frequently than expected The low overall mortality among the male chemists resulted in a larger than expected proportion of deaths due to cancer. The cancer excesses in the previous pro portional mortality reports on chemists mav also reflect low absolute mortality and not absolute excesses Anticipated excesses of certain types of cancers were not observed, possibly because of the use of absolute mortality rates, inadequate length of follow-up. exposure to hazardous chemicals by the referent group, or resfrx tion of case identification to active employees Deficits in overall mortality rates and m lung cant er rates were observed. These findings mav have been due to lower prevalence of smoking among the chemists or , disparate socioeconomic status or other tactors Journal ot Occupational Medicine/Vol. 23. No. 7/July 1981 OLI 6752 I I j j 1 , j i i I j j j j 4'* j ,j` nor* * `M'* *n th^nk L>' bruo* W k ,iffh ( orporg'** M#dif 41 Director of 1/ - f ,rt ''ii n v^po^.ft ot 'fudi. t>\ brirtn \w Mahon kif hjffi k Monson uf'J Urt^'d m A* ^n,rtn tor #*p<Utrmiouj|*u. dQvite Or Alan i Momson lor her**v *-<* r> the manuscript Cfr Vafin C Brfwyitrr lor his administrative assutante ^cirev t l Gidnev for her programming assistance William f Fd,en*edtner Brian H Wright, and Ceorge W Zetvas a>sO provided program ming assistance Ann D Monson was the nosotogist Clerical dunes were per* formed bs Mary Donahue lour*e Mowbray Cern A Nardo Lisa P Ranken and D^iores Saunders Kathryn C Buchanan Dorn Carmo Gertrude M Crowley Var:n* D'Domemcis and Mary Oloughlm provided secretarial services References 1 U fP Fraumem |F Ir Mantel N, et a! Cancer mortality among chemists I Natl Cancer Inst 431159-1164. 1%9 2 Li FP Suicide among chemists Arch Environ Health 19 518-520, 1969 J Milham S |r Occupational Mortality in Washington State. 1950-1971 L1 S DHEW' Public Health Service Publ No 76-175 Washington DC US Govt Print Office. 1976 4 Petersen GR and Milham 5 Ir Occupational Mortality in the State ot California 1959-1961 US DHEW. Public Health Service Publ no 80-104 Washington. DC, US Govt Print Office. 1980 5 Olin CR Leukemia and Hodgkin s disease among Swedish chemistry graduates Lancet 7991916, 1976 6 OlinCR The hazards of a chemical laboratory environment -- A studs ot the mortality in two cohorts of Swedish chemists Am Ind Hyg Assoc / 39 557-562, 1978 7 Occupational Mortality The Registrar General's Decennial Sup plement tor England and Wales, 1970-1972 London Her Maiestv'* Stationary Office. Office of Population Censuses and Surveys, 1978 B Study unveils British scientists'way of death. New Scientist 80'93, 1978 9 Curalmck L Mortality by occupation level and cause of death among men 20 to 64 years ot age. United States, 1950 Vital Statistics. Soeoa/Reports 53 141 1963 10 Kupper LL, Mc.Michael A|. Symons M|, et al On the utility of p'opomonal mortality analysis I Chron Dis 31 15-22. 1978 11 Annual Report. E I du Pont de Nemours and Company, Inc Wilmington Del E I du Pont de Nemours and Company, Inc, 1956-1977 12 Pell S O'Berg MT. and Karrh BW Cancer epidemiologic surveillance in the Du Pont Company / Occup Med 20 725-740.1978. 13 Monson RR Analysis of relative survival and proportional mortalitv Comput Siomed Res 7 325-332, 1974 14 Cutler SI and Young IL Ir (Eds), Third National Cancer Survey Incidence data Natl Cancer Inst Monogr 41-1-454, 1975 15 Miettin.- OS Comment I Am Srar Assoc 69 180-382 19U It* Pi-ll > .-"{I U A.on/o DA A hve-ve.ir mortaiuv Studs ot alcoholic- I L'ccup Vfeo 15 120-125 1973 17 International Ciassitication ot Diseases, Adapted tor Indesmg Hospital ken'i-tis r.. Disease and Operations US DHEW. Putilic Health venue Pubt No 62-719 Washington. DC y S Cosl Print O'tice 1U62 18 Eighth Revision International Classification of Diseases Adapted for L se in the United States U S DHEW. Public Health Ser vice Publ No 67-1693 Washington, DC US Covt Print Office. 1967 19 Olm CR and Ahltiom A The cancer mortality among Swedish chemists graduated during three decades Environ Res 22154-161, 1980 20 Emmett EA Occupational skm cancer A review / Occuo Med 17 44-49 1 975 21 Mason Tl, McKay FW. Hoover R, et al Atlas of Cancer Mortali ty for US Counties 1950-1969 US DHEW. Public Health Service Publ No 75-7B0 Washington, DC. US Covt Print Office. 1975 22 Fmseth K Suicide among women physicians IAMA 2371693. 1977 23 Qecoufle P Thomas Tl. and Pickle LW Comparison of the pro portionate mortality ratio and standardized mortality ratio risk measures Am I Epidemiol 111 263-269. 1980 24 Decoufl* P and Thomas TL A methodological investigation of fatal disease risks in a large industrial cohort. I Occup Med 21,107-110. 1979 25 Cole P and Goldman MB. Occupation, in Persons at High Risk of Cancer An Approach to Cancer Etiology and Control. ). F Fraumeni. Ir (Ed) New York Academic Press, 1975, 26 McMichael A| Standardized mortality ratios and the "healthy worker effect" Scratching beneath the surface. I Occup Med 18 165-168. 1976 27 Ott MC. Holder BB, and Langner RR Determinants of moctality in an industrial population I Occup Med 18.171-177, 1976 28 Kahn HA The Dorn study of smoking and mortality among United States veterans Report on eight and one-half years of observa tion Natl Cancer Inst Monogr 191-125, 1966 29 Hammond EC Smoking in relation to death rates of one million men and women Natl Cancer Inst Monogr 19127-204. 1966 30 Sterling TD and Wemkam IT Smoking characteristics by type of employment I Occup Med 18 743-754. 1976 31 Use Habits Among Adults of Cigarettes. Coffee, Aspirin, and Sleeping Pills, US DHEW,,Public Health Service Publ No 80-1559 Washington. DC US Covt, Print Office, 1980 Protecting Beliefs The scene has become all to starkly familiar. The pop-pop of a pistol. The panicky faces turning to see where the bullets are coming from The great leader, wounded, being hustled out of danger in a speeding car Police struggling with his assailant. And we can only wonder at the ironies of a world in which truly liberal men, with a deep-seated belief in the sanctity of the human soul, the worth of individuals and the essentiality of political freedom, are the victims of assassins while tyrants are not. The only lesson we can draw from this is that good and liberal men and women everywhere should be reminded by such events of how important the beliefs are that we are trying to protect. -- From Review and Outlook And Now the Pope *n Tht v\a , Street lourml. May 14 1W1 ~r~ z Mortality and Cancer incidence Among Chemists Hoar ano Pei OLI 6753 mm