Document 0qg1p1V4jz00aaMGXdwg9EqaO

FILE NAME: Avondale (AVD) DATE: 1967 DOC#: AVD167 DOCUMENT DESCRIPTION: Article - Journal of Occupational Medicine Mortality Pattern in a Cohort of Asbestos Workers Jo u rn a l of ^ f ^ fccupational MD-462 Mortality Pattern in a Cohort of Asbestos Workers A Stud}? Based on Employment Experience THONAS F MANCUSO, M D and A.VAS A EL-ATTAR, M B , Cu B . Sc D , Pittsburgh, Pa. I N pr ev io u s pa per s, the basic epidemiological workers exposed to asbestos and specific causes approaches to the study of industrial popula- of death i tions, demographic and cohort, were discussed, For epidemiological purposes, die question and their potential contributions and limitations is what combination of resources and methods cited.' *-5 Recently, we have considered several can be brought to bear, in the absence of com facets of long term studies, the dynamic pany data, to establish long-term epidemiolog changes of a cohort and their influence on the ical studies of industrial populations, and to ap- .statistical evaluation of a cohort's progress and pioxmiute e\ a on mental exposure and the de observation over time, and the concept of the gree of usk for the population under study. In successive cohort approach.4 5 In these studies, the epidemiological evaluation of environmental our objectives have been to improve on the exposures, duration of employment, length and methods of studying industrial populations over continuity of exposure, and piovision of some long periods of time and to cast some light on consistent measurement of employment expo .'particular aspects of the occupational hazard tor the population at risk. sure over the years constitute the initial broad separation of the population under study and a The purpose of the present paper is to carry lout these objectives pertaining to methodology .by', introducing an essential refinement--the 5characteristic of "duration of employment"--to the cohort studies established through the same ,national resource (Social Security records), and .to determine what relationship exists between V-- ^------ - From the Deportment of Occupational Health, Graduate method of defining the population more likely to be at risk. This measure of risk--duration of employment--was not included in our earlier study1 because such data were not available at that time. Since then, following exploratory ef forts which adhered to the policy of the Social Security Administration to safeguard the confi dential nature of the data, arrangements xvere completed to obtain information on duration of School-of Public Health, University of Pittsburgh. Pitts- TWrgV ra. V.Supported by Research Grant CA 0T588 from the Na'n ^Jnatltutes of Health, V S PublicHealthServ.ee e m p l o y m e n t o n a statitival basis for CdCl] mem ber of the cohort. The principal hypothesis being tested is 147 N ' - 148 MORTALITY IN ASRESTOS WORKERS OccmmS) whethei the duration of cumulative employ ment experience among workers in the asbestos products industry is related to an increased mortality rate generally for all causes of death and particularly for specific underlying causesof death. W agnei, in his pioneeiing observations of the relationship between mesothelioma and asbestos exposure, focused attention on the biological effects of asbestos, which study has served as a basis for international research and effort per taining to experimental pathology and epidemi ological studies.'"9 The importance of duration of emploMiient in such epidemiological studies (for evaluating the strength of association be tween asbestos and malignancies in longitudinal cohort studies) has been well recognized by pre vious investigators Unfortunately, this type of information has been quite limited and not gen et ally available, consequently, there are only a few cohoit icpoits on asbestos in the literature which include some tvpe of leference to dura tion of employment. Further, in each study, official vital-statistics data of the general popu lation of the country, state, or county were uti lized fm control purposes. The limitations of the use of the genera! population for contiol purposes lias been tecogmzcd D oli1' defined and o b s m e d a cohoit of men emploved m scheduled jobs m an asbestos tex tile plant who had been emploved for 20 veais oi inoir m the s.mie plant He concluded that the avei.igc lung-cancer risk win m the oulei of 10 tunes that experienced by the geneial popu lation and that the iisle had become piogiessiveh less as the dm at ion of employment e \poxme under old dusty conditions decieascd (following the institution oi ceitam legul.items and contiol measmes at a given point m time) These ohseiv ations w eic tuithei substantiated by Knox et ul m a continuation of this basic stmlx,` " which lcvealed a clccieased lung can cel usk subsequent to that point in tune ( 191") In this in.umei. the observation ot the effective ness oi the env noninental contiol ineaxmcs. \ e the d eu ease in asbestos cvposuie lesultmg m the deeiease ot lung cancel, augmented data on the ptevumslx established direct association b e tween lung cancel and asbestos exposme it- was also appaient from Kuo\ ami Doll's ohscivations that the effectiveness of the em iluumental contiol measmes at vaiious penods could have an influence in testing uui piuposed Itvpothi sis It is evident that a 10-vi'ar penod of nuplov inent esposm e in the a s b e s t o s indus try during 1920-1939 would be complete! ferent from that of 10 years of employm the same plant during 1940-1959. This was' of the essential reasons for using the gen cohort method for testing this hypothesis, Braun et al ,15 in their study of asbestos in Canada, established a cohort at a given ^ in time (1950), the members of which had more years of previous employment; the in gators observed this cohort for a period of 6 years. The cohort composition was chi . terized by varying lengths of employment) they related to other factors such as smoking and weighted-exposure categories. An analyst of this study has been made,18 citing the in f i ! ent limitations and the lack of justification foi the negative conclusion derived. ` Mancuso,3 through the use of 1938-39 Social^ Security records, established a company cohort? of asbestos workers who were observed to mid- i 1960 In this study, the need for data by dura tion and the development of more appropriate' controls for industrial cohort populations w expressed and served as the basis for the present' xtudv . Sc'hkoff et f t l 17 utilized union records to es tablish a cohort of insulation workers as of 1943, m which group the elapsed time from initial exposure was the essential criterion, characterizmg the cohort as those with a history of 20\ vears or longer .since the first exposure to asbes tos dust The consistency of employment for this occupational trade group has been histori cally ieffected in the expression "once a pipe coverer. always a pipe coverer." Consequently, the duration of employment may have been extensive Enterline,1'* utilizing the Social Security ap- pioach, established an industry cohort, consist ing of a number of the asbestos-products plants, ot workers who were employed at some time duung 1948-1951 and observed to nud-1963. Cohoits xxeie established m the same manner for cotton textile plants, which together with the specific death lates for the U S xvere uti lized for comparable purposes Enterlme fur ther cited the difficulty of interpreting findings m the absence of data on duration of employ ment. and the limitations of the Social Security data for this purpose. We have been able to m ei come these problems in the present shidv The piesent study constitutes an application nf the ohset cations denved from our explora tions in methoilologv of studs ing industrial pop ulations It differs from pies ions prospective April IM7 MANCLSO & E L -V m R 149 asbestos studies in the basic utilization of a generation cohort ami internal contiols, with gradient levels of employment as assesssed through Social Secuntv teeords The pioblem of "adequate contiols has been a major obstacle m industnal health studies and is further accentuated in p iosp ectn e longi tudinal studies covering a period of main yeais This problem, too. has been consideied in om present study. The primary emphasis and dncction of the cohort study was to 1 Demonstrate the method of utilizing an internal control with a geneiiition eohoit, accoidmg to age and specific lesels of em ploy ment expenence foi a company under studs (as derived from Social Secuntv data) 2 Esaluate the effects of duration of cumu lative employment expenence on the moitaht) pattern of workers exposed to asbestos, specifi cally in relation to malignant neoplasms, eaidiovasculur diseases, and asbestosis To our .knowledge, the present study is the fust repott to provide such essential data pet taming to all gradients of levels of duration of cumulative employment experience m an asbestos industry, and the relationship to the moitality pattern m a yvell-defined "total" population at risk, fol lowed for a long penod of time (24.5 years) m "which a generation cohort method and internal control is used. Method of Study The study was conducted m the same manner as the previous asbestos study1 m the establish ment of the cohort for 1938 and 1939 through Social Security records, the method of follow up, and the determination of the deceased and .the causes of death. `Data pertaining to sex, color, year of birth, 'date of death, and a com plete employment hispry in the asbestos plant (by quarters of each year) were made available to us by the Social _urity Administration for the living and the deceased from 1938 and 1939 to mid-1964. The additional data made it possible to classify the [population by sex, age, and cumulative employ ment expenence during the period of 1938 to mid-1964. The dynamic changes pertaining to ^ga, cumulative duration of employment, and Years of observation in a long-term cohort study ^discussed in a previous paper1) were considered *.the computation of person years and analysis th e data. Age The colioit was classified in age giuups of 15 24 25--44, 45-64. and 65 and over. The date foi which the age-specific death rates weit* cal culated \y.is the date at death, for the age at enhance generation method, the age was calcu lated as of 1940 The limitations and m euts of the \ aiious methods of compat isons. age at deatli and age at enti ance,4 seised as a basis for om selection and classification ui the piesent cohort In age at 1940 Cumulative Employment Experience Each sex-age gtoup was classified accoidmg to the cu m u latee employment expenence they act|itncd eluting the penod 1938 timmgh imd1964 mto tlie following 5 levels I Ullltlfftlf */!/ " i f i l H H t t J } H t t f JKP I 11 UI IV X /, t u f t h l l f m t ttf r J It t H tl* r Ct/r } 0 t- 2 0 2 1-70 7 1-12 0 12 1-170 17 1-27 5* Death l.ites for the selected underlying causes of death w eie calculated for each sex-age lex el of cumulative employment expenence and foi Level 11 through V combined Development of an Internal Control In the present study, employees of the 1938 and 1939 cohort who had a cumulative employ ment experience of 2 years or less during the penod 1938 to mid-1964 were selected as an in ternal control. Average annual death rates for employees who had a cumulative employment experience of 2 years or less (L evel I) were computed by sex and age group. For each sex and age group of employees having cumulative employment experience of more than 2 years (L evels II, III, etc ), the expected number of deaths was de termined for the selected specific underlying cause of death by applying the average annual death rates of the employees having cumulative employment exjperience of 2 years or less for that age group. The standard mortality ratios (SM R ) were calculated based on the observed and expected number of deaths due to under lying selected causes of death for age at death and age at 1940. ' *mcnt experience for an era- plnvee who uhs a h \e by mnl-l9G+ and has a continuous em ploym ent in the asbc&tos p la n t since 1938 is 27 5 y ears 'ijpmM i lU'.tt 0 | JfJJ) %[ j j i ' Rilutti' r>tu u jjj H Ul p J|/lj >\ > t|V ( I ) >ls<i|-.K|>r |)Il 1- (1 ) ltd Jij n || ju |llsl|liiini jtJi HTlij i m " 1 .tip J 1V Sl[|l || l|l Ul 11 MX (1) ppit& piiu ` (L) jUtltM.TJM <r) SIM)|>.Hj>ll ( J ) 9'|U98I|) |iiu q 0 ) >i j 1*1111 M* |t iyi ) >N |nu 'i |r ju i Hpu i *>l mji > p o d M t *ti nui q ju jp |U J^ b J Il SjU J V\tj- U, JJKpJO J bJ HplijuJ l>| (,4 1 " > MAI u 1 d u iiju >>u -IO ' >p ijllll.ij r i'1" jl IM *1 V|.ii| i , LS Ifi 9 -- -- -- I -- I P t I 91 II S l --- [ 61 t 6 U -- -- ---- 69 8 6f 9t t b S '0 1 fi. s..M ` UV -- -- -- -- --1 -- 1 '''< h s a 5 --Z 1 I -- ;-- -- -- ---- *--- -- f- i i 19-S S I I -- , S t Z Z Z --t t 1 SI il 1- 1s -s i 15 05 t t' sz zz fc 9 a 9 -- t 5 1 11 u 9 61 PI c h l Z 19 si- SI 11 -si s r L\ 91 l oy L t SI Si -- UH so s 1! ~S5 t S S ---- 91 91 51 ci -- 51 51 -- 1 5 -S 1 kjtvin j i 181 s o t Q L 1 --. 51 t b tu It ZZ 86 89 o t 9S1 eu PI la ta -- .i 7 U (.i tu y / : t ) SL 61 a s 6U HL 19 ( p / -- L Z 1 12 01 -- m f)l t Ul (le 9 SI H O 51 U 91 1 8 t 1 if 9 H 1- P -- U 15 1 L 7 </ t 7 <1 (o 1-1 Cl ) ai ( t u ,! ! 1) m /anttfntftfinJn kjink u b tl 195 88 9 -- 9 51 t 6 Sl t zz as 95 m au 611 L 1 ni on S I IVJV 1 7 <) (d : t . ) U hi y. lr'f 151 c i r Ot 1 i i 1 -- t 5 01 91 51 85 h 151 i 1 1 11 151 f l 1 l / 7 (. l u ) / S951 su> t C 1 1 9 f) (il 1 SS Si 5 011 lit ill rn o r DU V.TU- |\ 15 1.\ l l ^ ( i) 1 S 1 9-SS' [0 is-si so 1 1-s i IS 11 -S5 51 ir-si i 7 tf W / U*1 * `ii >tU.i / " >i*\ *{ CI ) "V l ( | >u> ( ' ] ) JNIAI'I vw>fcj ( i \ I ^ M ( I mill IS l( [ M II il iiss s I ) ) i,HJNHU/V\ S AMVJ ISO") S D I S I t l s y IN() 4 0 i n a i \ l l \ ( | ) 'IV IO X 41> .I d - \\l ) I Kl ,| I "b 1. T a b l e 2 . C a u s e o f D e a i i i im 1 9 - 1 0 - m i d - 1 9 6 4 F o l l o w -u p o f A s u l a u i s - I 'j .a m W o h k i hs ( i s C i a s s i h i i v T i m ) * r \ t f t r f r H W t i l r t f i X t <//// m t u t 4 4 f t t m l i t < Mutt s f't limit a ( ttf tftitfh unit ctulf in in ,it / ii in n 1 Ut t ' l ' l ' . i 11 i l l Toi \L .mi Tuberculosis, all forms (001-020) 10 All neoplasms (140-219) i>5 All malignant neoplasms ( 140-205) 84 Malignant neoplasms of digestive oi gaits and peritoneum (150-159) 26 Malignant neoplasms of peiitonemn and! or mesothelioma i ,8 Malignant neoplasms of lung, brumlitis, and ti.iclic.i (162-163) 55 Unspecified inatignaiil tieoplasms ( 199) .5 All athei ucuplasms ( 140-149, 160 101 164-198 & 200-239) 10 Caidiovasenlai diseases (330-334 St KKl-168) 1 12 Diseases nl lespii.itois system (470 5271 45 Diseases of digestive system (530-557) 11 All oilier (..loses 39 Total Population L and D 1205 49 8 61 50 70 51 5 (> -- 1 -- i 13 22 11 11 22 I 1 11 21 11 14 22 11 1- 0 37 t 1T 1l 1 5 9 <> 3 It) ft -- 2-- i - i i >t * 25 to 20 51 ,s > 9 to 11 11 s --0i 23 i r. 15 9 t 7 3 121 149 159 7*3 IM 22.5 !s 9 -- 1 -- 155 15 1 11 1 11 1 -- - -- 1-- >11 --1t -- 1_ _ ____ 1 77 19 'IncIiuUs - tndt\tdu.iU ut Vilnttn ,isht shisis, kns rt'|K>rh>d ihd<.<Mi 11 r\ in ih .S Nl1MidiM i.him ! di ill t'l liis jrr*mp af n<u|histi5is imhuhit .in |.irt ui m.ili^u.int in 1'slllN411lip st13i or>_,iis iid 1*Ill'llli Ulit mu i a. thilumui of jthura J'il tiiitlis. in Ilk ni.tii; mul t]i thi to tin* h m . d i s t u n d m hi .isIm\ I hm % n 5 -- 1 1 _ -- 1 2 1 _ I 10 uti .in. I (> -- 5 ! 1 1 _ 1 3 _ _ =>7 hi |u< ---------- ir >iniT i-a m n i ! w in i ,Sj,\sinni) M u m u h x K \ jio ( S M R ) R asi i>on ivsehm d ( O ) and E m 'l c ie ( E ) N u M a tn o e D eaths D ue to S l l K 111! I ' M HI MM ( ' \ l . S I VMl I III, M o t U A I I IT R Al ES ( 1 5 ) Pi;|I 1 0 0 , 0 0 0 P u r U LAI ION HJH A(.E A1 1 9 4 0 AND \i i \ i Ui mii \ \ u i v , Ashimos W oklehs Srwmi ( s r s T ext) Jiff of /*' /f# A p e at Jcnth > > 4' <f >,} (22 over -`f So-H i!J ij*over *`ft* I,,.!,., a i' i> t: o t: c> /; o li O E O E O E lui M \,i % s T 1 12 17 1 12<I 10 S IS 7 1 -- 0 8 .12 21 3 16S 65 7 81 465 II sxu: \U Ml *|>l. \i. ii w -jn sfc n o j fi) l( 1 17 2 H ISMl 72 s 5.H IjO -- 2 5 12 i) .) -- OS SOS 1)> 0102 2.MU 1INI i 5S25 1J7 252 2(i 12 0 4 00 102(1 SS<> 3252 -- -- u.s -) -- 04 -- 84 Jilt 200 451 11 6 5 107 6 2403 940 25 48 17 9 687 256 14056 8067 174 13 7.7 2256 1345 SMI! (-- ) m 217 (+) \l> -- 1 2 10 1 0 12 4 () (-- ) 168 268 168 4 1 0 15 9 0 3 00 m{ iiiii'shvr iiiu in'* H -- 1 M2 20 S.S0 205 39 16 215 128 521 -- tltl JM'I lIlMl/'lilll S \|]| i- -i 5 10 .100 i n o -1 v)) 245 167 (+) \l.kfimi.ini IKup[ (MIIV \ . i 1 1)0 ! 2 6 3.0 1 00 o| p i ilmuMitu ,id ' H TT -- 221 1 IS 89 43 174 --- III UKMllliellillll.U X\tli 1 !-> 150 201 (+ | - 3l >l Ihhu mI*li<wk Ini', & N0 n 27ID0 12fS> N i0l 7s9o0 I d H2 0--0 394 0--0 30210 19208 8685 137475 fyi*: 11At lu ( 161 i(v 1) NMU loSS It 1 (+) (+ ) 234 65 M t l J^liilUl (.- No 1 (HI 1 00 1 00 1 00 6 00 1 00 % lu <1 iK'upl.tsms h M -- 74 -- 810 -- 0 -- 86 -- 174 -- ( I1)'!)) SMI! ( i ) (4) ( t-) (+ ) <+) (+> ( MImt m'upl.isms Nn - - 1 2 7 5 55 1 (ID 1 00 -- 0 4 2 4 9 6 00 4 00 ( 1 1(1-1 f i IN)- 161. 11 -- M too 70 207 -- 810 -- -- 84 19 48 86 -- 694 -- '1 If.l-l'JS 200-210) 1)im*is* <*of r SMIt (-- ) 1 27 I2fi II) JO 7 (+) fift 22 0 (+ ) (-- ) JO 7 I \ ,t\t nl.u s\ stem 11 27 65 770 227 JOIfi 1024 SI 61 5825 1HO H I 6 100 If) SMIl 10 210 700 140 41 4 49 39 48 82 (+) 63 38 8 901 556 162 (+ ) 50 34 9 8677 6050 143 1Jim ,>.xui li".pn.V llll V \\ Ml ( 170- 727) \ 0 m`v| i>m>. (">212) \.i II SMIl Xu 1 00 __ ( I-) 2'! 3 7 127 5 ! 017 10 0 0 IT (10 1275 -- (+ ) 12 0 0 4 33 39 32 J22 2 00 31 0 0 443 -- (+> 26 0.0 6 00 1041 -- (+ ) .3 0 0 11 270 -- S80 -- 19 -- 372 -- 521 -- s\m D immsix "f (iiK<'sO%c No msIi 'hi (571)-5S7 ) H (+ > (+5 1 00 4 00 5 00 1 00 27 -- 57 -- 369 -- 816 -- (4-) 4 00 39 -- (+ ) 2 00 29 -- (+) 5 0.0 521 -- OiUn tansos SMR No n s\in (4 ) 2 7)7) 75 102 71 (4) 25 7.41 528 100 .110 (+) 12 4 0 886 295 300 (+ ) 3 0.0 2449 -- (+) " 04 -- 84 -) (+ ) 9 6.5 87 63 J38 ., __ ... -Jf. (+ ) <+) 24 9.0 7 39 343 ,...128 1215 672 N /ili. . I "im-itl UthUirv tin lUIn fro m SSJX tnuly. ` M l III itftlthM itn nr< i.in ll|in M l l q u ' l i t 1 c a t l i n g U r I h C o d # d \ Mil nruin* o f iim U iii^ n l tuup!in u ^ n iln o til M i Yol. S No. 4 - April 194? M\.\C LXO 8 EL-A ITMi i33 Characteristics of the Cohort The asbestos plant had unK white em ployes in the yeais the colioit was selected. 19 38 oi 1939 (Table 1). About 855 ot them weir male The age coinpdiisnn shown! a sonsideiable minibei of voting emplov et s Specifically. mon than two-thirds oi the emplov ees m the cohoit m 193S oi 1939 wcu* m the age gionp 15-34 teats in 1940 During the penod 191S to mid1964, the cumulative emplov incut cxpei leno classified by sex and age at 1940 toi the cohoit population is illustrated m Table 1 It was noted, for example, that about 255 of the male em ployes weie m Level 1 2S'. weie in Lew el ii, and 477 weie in the combined Levels 111 IV, and V of cumulative emplov incut expet icnce in the asbestos plant During the penod 1940 to mill-1964, them were 330 males and 31 females m the plant co hort who died, excluding 14 wai casualties death at sea, and 6 deaths dining 1938-1939. The distribution of the numhei of deaths in V. level of cumulative emplovnieut expeneiice among the cohort population is illnstiated in Table 1 For all levels of cumulative emplovment expei icnce, there weie 330 deaths ( 2 6 6'c) .in a total male population ot 1265 and thete ,s were only 31 deaths ( 13.67) among 228 total female employees IT findings In our study the cohoit population tcpie'sented the combined cohoits of those employed 'in 1938 and those whose first employment was ^recorded by Social Seemitv as being in 1939. ^Information was not available to characterize the members of the cohort bv fiist employment frithe plant prior to 1938 and this, consequent ly, deferred any analysis by the successive co- ort m ethod5 Howevei, in our preliminary .analysis of the individual cohorts, employees of 1938 and those of 1939, we found an apparent "Terence. The 1939 cohort employees, repre- ting mostly new employees, sustained a low , mortality for all causes of death and for the lected specific causes of death under study. iO f the total 1265 male employees in the 1938- cohort, there were 328 male employees ,'at belonged to the 1939 cohort, of which there were 47 observed deaths due to all causes in clu d in g 2 deaths c a u se d by- m a lig n a n t neolasms of lung, trachea, and bionchus, and none ue to asbestosis. Of the temammg 937 male loyees in the 1938 cohoit, there were 283 deaths including 31 deaths tin- to asbestosis and 13 deaths due In malignant neoplasms ul 1 1 1 (lie hum tinchea and bionchus rssonci the bi tti i sin vital tin (ln>sc ul the 19 39 cohoit and the u hs t i vat mn that none ul the cases ol asbestosis occul t ed annum tbusi whose u colds appeal ed m 1939 as u-coideil bv Social Secmitv when c o m p a n d to those whim i< colds a ppeal ed in 193-S could In din to flu influence oi pieviniis emplov tut ul puoi to 193S in the same plant among the 19 IS i n h oi t and also because of the eilectiveness ui die e m innimi nt.il changes ami iinpiovuni uts m subse quent ve.us Tbeielote mu obsi i v.ilmic on u duction oi iisk although limiti d .m m agiee- iiu'iit with the oliset i ations indiiati d bv Doll and h u m rt ul ' ' 11 The subsequent findings {winch follow ) t i late to the combined 1938-39 cohoit of emplovecs ol till* asbestos pioducts plant Table 2 cll.U actei i/es the niniihei of deaths hv the 1111dei lying selected cause's of death as noted hv se\ and level ol cumulative cmplovini iit expeMeuce Among tile males theie w tie 35 malig nant tumois ot the lung (425 oi .ill malignan cies). of winch ~ occ'iiued in Level I (0 1-2 0 cumulative ve.us of employment) Of the 4 3 deaths due to icspiiatoiv disease, 31 deaths weie due to asbestosis Foi the females theie weie II deaths due to malignant neoplasms nnd of this gionp 6 (547) were due to malignancies of the lung (one was in Level I), and all of the 8 deaths clue to icspiratoty disease were due to asbestosis Theie vvoic S malignant neoplasms of the peritoneum and/or mesothelioma, iden tified in the 330 male deaths of all causes, 1 of which occuried in Level I. Table 2 provides the initial distribution and indication of the influ ence of dotation of employment As was seen in Table 1, the age gtoup in each corresponding level varies and consequently influences the ob servations lelative to duration of employment and specific causes of death Table 3 applies the average annual mortality rate by age and nuclei lying causes of death of the internal control (Level 1) to those with Cumulative years of employment experience of more than 2 years (Levels 1I-V inclusive), and as such provides an "ovei view" of the moitalitv patterns of the cohort, without relating to spe cific levels of employment It must be borne m mind that the internal contiol (Level I) is a sub cohort of the same cohort population and differs only in being charactei lzed by the shortest duration of cumulative years of employment ex- I'V--iifill iff >i4Tfc|| 154 MORTALITY IN ASBESTOS WORKERS Otfcupti perience { ? ........ I"1-) in ths asliestos indus try during 1938 to mid-1964, In Table 3 the mortality rates are calculated by 2 methods( 1 ) age at entrance, the "generation cohort ap proach," and (2 ) age at death, rire "usual age specific death rates." In Table 3, the SMR calculated hv age at death and age at entrance illustrated higher values as compared to the control. Most of the obseived additional deaths were due to malig nant neoplasms (specifically those of the lung, tiaehea, and bronchus, the digestive organs and peritoneum, and also "unspecified malignant neoplasms"), diseases of the cardiovascular sys tem. diseases of the respiratory system (specifi cally asbestosis), and diseases of digestive sys tem The SMR and average annual mortahlv rates tor ages 25-44, classified In age at enhance, uas much higher than the age 4.5-64 foi malig nant neoplasms ot the digestive oigans and of the lung This dilleience was moie inaiked foi malignant neoplasms of the lung for age 25-44 and was 10 times that of the control group. For the age- at death, the highest late tor lung cancer occurred in the age gioup 45-64 The .SMR and moitahty Kites foi lung cancer m tlie oldt'i age gioup 45-64 (as classified In both age at eiiti.iiice ami age at death ) illustiated tlie effect ot the `intein.il control" on the dilleience between the obseived and the ex pected When the expenenu* ot this age gioup with l i w l I imploi meut evpcneute id 1-2 w ,n s) is applied to the cmlesponcling age gtunp to di live the expected late, the expected i.itc would be luglici In xutue ol the influence ui eruplov ui< ut pi mi to 19 3.S fn this lespi-ct theiefme tin diffeieiice obseived constifiites a xr-tx t miser vutiv e estimate Effects ot Cumulative Emphnrnont Experience on the Mortality Pattern I i>i tin- purpose ot assessing the lel.itnmship betsten the nu>it.llltx pattern anil the dotation of i mploi im nt the rates In age at 16{d wen used foi the i ,u ions leasoris to be discussed To i uiiinn this n l.itimisliip. nimtuhh i.ites wenus< d as follow > all u nn 's all neoplasms malig nant ui oplasnts of digestive oigans and peutoni'um malign.iiit neoplasms ot lung bron chus and Katina taidim asciil.it diseases ( ex cept v.iwiilai lesions afh'cting the centi.il m ixmis ,w ii in i ,uul .ishestoMs Table f illnstiatethe o lisiisid the t spitted ain! the axti.tgt ii iro i,i) mi n taliti i.itis jit i 100 I)dll lot selected underlying cause of death and SMR a$ c*` by age at 1940 and level of cumulative e ment experience. The mam description of the result; seated in Table 4 is directed at the age 25--44 age at entrance of the generation according to the corresponding cause of i in order to lessen the possible influence of. vious employment. ' r`r-. All Causes of Death It is noted that, with the exception of l?j and more years of level of cumulative empTmerit experience, there is a consistent inc m the average annual mortality rates as cumulative employment experience increa For example, the average annual mortality rate, due to all causes for age group 25-44 are for 0 1-2.0 years (control group); 1091 for 2.1 7 0 years, 2280 foi 7.1-12 0 yeais, 6788 for 12.1 17 0 years, and .3398 for 17 1 and more years of cumulative years of employment experien The same holds true with SMR values wt in the same age groups, there are values of 207, far 1 1-7 0. 432 for 7.1-12 0. 1287 for 12.1-17.0, and 644 for 17 l and more years of employment expel lence All Neoplasms Table 4 indicates an apparent increase in the axeiage annual moitahty Kites foi all neoplasms as the cimmlatixe employment experience m ci eased Fm example, the average annual mort.ilitv u tes foi all neoplasms foi tlie age group 25-41 are 132 foi 0 1-2 0 \ears (control groupi 348 foi 2 l - i 0 veais 5 i0 foi . 1--120 xv.iii 3133 foi 12 1-170 yeais. and 1081 for 17 1 and mme yeais of cumulative employment experience The same holds tme with die SMR xallies xxhete in the same age gioup. SMR x,ifucs ,ue 264 foi 2 1-7 0 xeais, 432 foi 7 1-120 xe.ns 2 376 fin 12.1-170. and 819 foi 17 I and moie xeais of cumulative eiuploxmeiit Malignant N eoplasm s--D igestive Organs and Peritoneum 'I hole uas a total of 25 dentils in the nge group 2-5-61 as ot 1910 due to malignant neo plasms ot digestive oigans and peritoneum uillv 3 deaths occurred in the CODtiol group if) 1 - 2 0 xeais ot cumulative emploiment rvpi-i iincr 1 and 22 deaths occuned m the lughei I. xi Is Because ot tlie xeis small number of casts foi each lexi'l of cumulative emplovnient .md agi gioup if is difficult to demolish ate a ||) U -Yot. ^ 'Apnl (7 \H .\L IS 0 & liL-MTAH I'- relationship between tin- innit.ditx i.ites finm Ineopiasnis of digestive oigam and pnitonnmi and the cumulative empluvment expendin' The aveiage anmul moit.ditx tales. however wete higher for <iiJ the inmulufivv cniplovment experience of any age gioup than loi the contiol group. Foi example die aw iage mm t.ilitx tales foi employees with 7 I -J 2 0 \ r,us ol <.muiilative employment experience wax 12 times that 1 the contiol foi the same ag ginnp 35---1*4 ><,us Malignant Neoplasm*--Lung. Bronchus, anti Trachea As is noted in Table 4 the inueased nioifalitx rate;, in association with the iiiihmsc ol cmmil..tive emploxment expenenie is app.uont Ini the age group 25-44 yeais e g tates ol 26 lor <> 1 2.0 yeais, tates of 156 lot 2 1-7 0 yeais, !6 > bn 7 1 12 0 yeurv, and 1567 hu 12 1-170 xeais There was, howevei, a decline hi the moifalitv Tate for 17 1 and mine seats of cinniilahxe em ployment expo ten* It is eudent that the late and risk for lung cancel does nutcase with ^duration of emplox ment The degiee ol nsl: appears highest after emplox ment ol 12 xi.ux more At this stage of out investigation, xxc mot attach undue significance to the rate foi Hung cancel for Lex el I, since the data and spe cifically the Level-I employees' omplmment aie lited to that which occurrctl after 1938, and ye do not knoxv wh.it specific earlier yo.u vould represent the actual first yeai of employsent in the company--in contrast to the year as ^utilized in this study foi enhance into the coJ'fiort. However, Level l {(11-2 years) for age group 25--44 can he considered a possible over -estimate of the lung-cancer late of individuals this age group and lex el of employment e\ience. The consistency of the increase in ate, recognizing the built-in factors for sticcesJre levels of increasing employment, piovides additional support to the relationship of lung ancer and asbestos exposure. Cardiovascular Diseases Jit is noted from Table 4 that there is a con- ent increase in the avei age annual mortality iltes as the cumulative employment experience acreas ...~..iple, the average annual ttortality rates due to catdiovascular diseases tcept vascular lesions affecting cential nerv- *>*-T*--' f-- - 35-44 are 211 for -A ' ' - 651 for 7 1 - ... tnd 849 for 11 I .11id l l l f i c \ I'.tl s ol t limul.ltlx < i Uipirix |lie u | expendin' Tin same p ublic holds Him xxiilt 5MR x.tines wheir in the same age gituip (licit .iic x.dii(! nl ] >2 lot 2 I 7 <i \ t .us Sop jot 7 1 12 0 x i .us J45 loi 12 1-17 0 xe.iix and 40> lot IT I am i tunic xeais ol (.m ind,iti'i em plox metu expel lent e Asbestos is lit Tal>l< -1 e x c lu d in g the " u n tp xx it 11 1In h u l n( umitilafix e n iip ln v m en t c x p e tie ir u nl 17 1 and tunic x i,ii' the ,i\d.ig< amiu.d iiiiutalitx i a l e s an d 5 \ | H xalm s iik n a w xx itb iIn 11u 11 a s( of till1 l Ilttuil.llix c i mplitx m< lit t sp in nit Ini d ea th s d u e to asIxMnsis 1 hi i xam p le lot ai!i g im ip 2 3 --1-1 i.ites d m In ash< siosis xxik 0 i / c m ) loi 0 1-2(1 xeais 116 loi 2 1-7 0 xeais 241 fm 7 I -! 2 0 \ cat s 2 0 8 0 fm 12 I--I, 0 x i . u s and 540 Ini [7 I anil tiimi x i a i s ol i imiul.thx e em plox iiieot e x p el U'ix e 11 is of mteiest to noli that ainom2 (Ik (ol.il tl ohsem d deaths dm* to disease of it spuafoiv sxstcui {loi all age gioups ol emploxies xxito hast* wot hid mou* than 2 seats m tin asbestos mdiistii I (Iteie ueu* 31 deaths du< to asfi< s(osis, 5 deaths due to ihmnic mteistiital pm uuuima. .mil I death due to silicosis--a total of 47 deaths Excluding these 37 deaths limit tile 4l ohsnvod deaths the irruaimlei will he 4 obserxed x m u s 3 7 cxpi'ctcd fax svax denied by applying the axin age annual moitahtx late of internal contiol) This is au illustiatiou ot the fact that the excess m moitahtx among em ployees with piolongcd imnulatixe seats ol emplox ment experience is a tim* significant ohseixation and not due to anx bins of selection in the internal contiol Table 4 also pi ox ides i.ites and 5MR by age gionp, in which the cohoit is diaractei i/ed as of 2.1 or more seats of employment expemmee in comparison to Lex el f ( 1-2 yeais) The cohoit is also characterized as "ail lex els,'' i e , it includes Level I, which also compares the total xvith Level I as the internal contiol. These two additional characterizations of the cohoit {2 1 and more, and all levels) serve to illustrate the averaging effect m the former and fhe dilu tion effect tn the latter, which occurs in contiast to the rates observed for specific levels of em ployment experience foi the corresponding age gi otips. Discussion Although we have oveicome some of the limitations of our previous asbestos study'1 and 3=- l WM* *VMrlfetaa viti t I S i \ \ i i \ | i ! i Motil vi t t s i j i v U \ M O i> \ OlSM HM U ( O ) - \ \ 1> E V IN C IL I) ( E ) NUMHLli Of- D u V t t l S Duf.VoSk.Lfe.CnK1> I'M ni u\< ( u .m ( M I VW.ittun-, \ \ I 1 S (1$) 'i 11 1001X10 l'ui-ui aiiox Amonc. C ouom P l-ciiibu 1N Tfcvr 1'/ ft~ f f t'>i*!*>t 1-.-21 r>-11 i5-i> i * <Ni t \ t \n K SMU N.i U suu v. ' u SMU No U SMU "/ U f / ," H : 2 1S --- 20 r>2`6 __ l'J Jsn -- t -- 1 o7 1O .' h il ! 7 27 7 1IWJ 52s 2\ >7 U 11 1 77o2 2SU-1 277 O 2 1 1jMiT *>S2"> 2-SO .-..i . nt't>ihthr> i ! \i i t ir o u ): {i i: M1 < SUM<1 l 2 2h 22S1) 27 SS05 7 IU71 i n 2 is loo b 7 )2S M2 7 `J 2s M0 2 r> 5825 2S i o u 1 -- 2t -- i i 1 0 (>78S 52S 1287 )9 8 1 11518 2804 482 1 2 2 ljfii? .5825 18$ Hi t s p i n i mc (yr ) i7 $ avir o n 3 t ^ tuorfi t> ti 0 os -- 2 $8 -- 44 6 8 3398 528 644 31 10 7 126 2804 290 1 04 $5185 58-25 264 5 1 $7 132 1880 126 9302 18 14694 ti 7 238 58 37.1 528 356 .39 8 2804 317 7 1 5825 252 A ll levels O ti 12 182 152 1406 145 7136 21 12069 157 238 77 57.1 528 266 57 0 2804 254 10 J7 5825 207 a h . ' . h i I ' U s m s (140-239) 25-14 15-04 No H SMU No 1$ SMU Nti II SM II V i; 5 1> 5 7 7 1 6 6 0 3 14 17 42 93 nz US 1)2 570 132 3133 132 1081 132 598 132 -- 21.4 4 $2 2376 819 453 6 (. 36 6 25 6 26 8 34 20 120 886 1191 886 212 886 2080 886 2097 888 1920 886 -- 168 240 235 237 2J.7 , M M U \,V M A ' i \ l v * --l ijC L s iT I V II OHLAN'S AND r E M X W ^ V U l 1 l 1 O.l 0 0.1 , 'ia ~ - ' ? r j* 4 TT Wl IVI l 295 1\)5 ~>Mh 3.15 - ./\> a&e 47 14 3 435 132 329 . 32 . . 18.0 ' k * WAjUGNAUT froPL&fo----LL'NC, BBONF IH'S. 1 At 1IFA ( 1 0 2 - 1 0 5) 2 5 - 4 4 ' ' No! ` ' I R 26 SMR -- 45-64 N o .' 4 R 590 SMR -- 25-44 45-04 No. R SMR No R SMR 8 211 -- 9 1328 -- 8 1 1 186 20 715 1 2.4 248 590 42 12 279 11 2734 91 211 132 53 1328 206 2 163 3 1064 03 26 017 1 7 590 180 .3 0 1 1567 26 5939 I 1 7 317 590 59 6 03 461 2<> 1781 4 2 3 1048 590 17S CARDIOVASCULAR DISEASES (400-468)* 8 651 11 3901 2 6 211 309 37 1328 294 O 04 1044 211 49 > 20 38 7279 1128 548 II 27 819 211 40) 17 5 1 1456 1 128 3)5 19 1 S 270 26 1038 9 8 2 664 590 109 11 N 8 170 211 221 59 ISO 4 r,> 1128 128 25-44 No R 45-64 No R Asncvrosis (523 2) _ 5 -- 116 -- 1 -- 248 -- - 3 -- 244 -- 5 -- 1773 -- 4 -- 2089 -- 5 -- 1713 -- 7 -- 510 -- 1 -- 262 -- 19 -- -- 270 -- -- 12 - -- 5V> -- *Kx< )l v a s c u la r lesin* n f f r c t m g C S S 20 2 8 185 26 713 l) 120 040 59o IOS 41 179 68 1546 22 8 211 ISO 27 O 1 )2S 252 19 -- ITfi -- 12 -- 591 -- 3W lo o MOi. '> WOnKtie some of the problems inherent to prc., studies m general, there still remains the ba.,-- limitation of establishing more precisely the population at risk, as defined by department and occupation m the utilization of the Social Se-. curtly approach in establishing company co horts The total population of a company may not be at risk. It is more likely that a smaller group of employees in specific departments and/or operations rather than those throughout the plant would be more directly exposed Con sequently, the asbestos-company cohoit utiliz ing the Social Security apptoach constitutes a conservative estimate of iisk because of the dilu tion factor of including all employees. This `dilution factor' was present also and probablv was augmented m Enterlinc's asbestos industry study, which combined a number of asbestos companies 1' It must lie icahzed that employment data prior to 19.3b are not as tillable from Social Seciiutv records and tins unknown length of em ployment prior to 1933 could have some beanng on the interpretation nf observations. It is well kilimn that poor employment m the same oi m .i difftient plant depends on the age of the em ployee m 1949. Tbeiefoie, tin example an emploxee .hoso age is IS by 1910 is assumed to luxe no thdiistii.ii einplovinent pnm to 193S and an rniphnie whose age is 4b In 1940 is assumed lo have about 30 xeais ol emploxinent pnoi to 19 >S since age 1*S is coiisuleied to he the fust age of actixe employment The classi fication of (he u>hoit In level of cumulative emplnv mi nf expel n nee vi Inch is based on the eui- ploviueiit lei old dm mg 1933 to mill-1964 docs not tli'Hlon- n-[in sent the actual level ot ciiinu lativ t i mploy meiit expenence since tlie Inst ve.u ol emplox meiit m the asbestos plant could not lie detu iimieil This is spiuficnllv hue 1m the nldei age gmnps, as nt 1940 I'm i .ic.Il Ii m I ol euiplox meiit the classification foi (lie vuulig age giuup fit* 17-24 ! is considered In lie the actual level ol t mplov meiit in the aslustos plant since this age gimip lias no miploxmiiit pi mi lo 19 3S CouseipH-ntlx the apjiiicatiou <4 l.evel I as an mtiiual contiol loi the age group 15-24 pi oxides the actual c o m pal ison between the vaimns levels of cumula tive emplox ini nt expenence In the older age gi mips lim u 'M'i. the i ompai attv<pic tin e ts chi li u ut 1 oi example in the age giuup 45-64. lit. ie is a xntttl oi unknown emplox meiit pilot in I93S winch could axeiage to 27 veals (4.3 -- IS - 27 1 f i v e ! 1 lot the nge giuup 17-6 f ' " ' .cu u> G.i-2.0 years of cum'' 1.. m in i smeripnce during the period mid-1964, could actually represent a hi level of employment when the unknown*' ployment nnnr *n 1938 1S also considered. The age group 25-44 lies between the'* age groups, 15-24 and 45-64, relative to 7, employment experience prior to 1938, . effects on the employment classification are f sented. Consequently, any comparison be' Level 1 and other levels for the older age gr* represent a conservative comparison. In i when the employment prior to 1938 is acH then the Level 1 for age 15-24 could be sidered to be the "actual" Level I, and for agp* 25--14, when this prior employment is addedj Level I could be a mixture of the equivalent oh Levels I. II, and III, finally, for age 45-64,,' Level I could be a mixture of Levels III, IV; and V. The mortality rates for Level I used in', the study, therefore, would for the older age groups constitute a rate which represents that: of a level of employment that exceeds the limits of the designated employment classification Foi age group 45-64, this high rate of Level ft is earned through as the control comparison in the development of the expected rates and SMR m each succeeding level of employment experi ence and for each ol the various categories of cause of death For these leasons. we have focused on the geueiation cohoit utilizing the age group 25-44 at cufiance as a homogeneous cohort, which pun ules a mote lepresentative indication of the [iiogiessiou and changes of iate according to v,nioiis levels of employment and years of expei iviiec Since then.' still lemams the limitation of not knowing flit* einplovinent prior to 1938, (he Kites dom ed will, in tins lespect, constitute a umseixative estimate In this method of es tablishing moitubtx late's, however, the use of ut mteiiia! control ot the same age gioup (age at enhance) equalizes the pievious employment lac tm In the age-at-entiance method, all of the population of the specified age gunip will grow nldei l>v a constant nunibei of years during the pound of obseixation (1940 to nud-1964) This aging process, however, would not influence the i-suits since the SMR and the expected nurnIxt ot deaths are deitxed by applying the axer.iiio .iniiiial niortalitx Kites fiom the mtcm.il conUot ot the same age, which is heated am! nbxeixed m the same maimer Thi' mean dmutiftn of em ploym ent and the V0I. 9 No. 9 Apnl i W MANCl'SO 4- EL-ATTAR 159 degree of en\ ironmentnl expoviie prior to 19% would be the same fot any sjnnlai age giotip and different for tanoos age gioupj, as classifier! by age at 1940. Similarly, previous medical catv prior to 1940 would then be the same as well as for subsequent sears, but will van with each age gioup. In this method, classifying the u>hoit by age as of 1940 and follow ed for 24 5 sears provides a complete mortality pattern of a generation of each corresponding age gmup during the period of observation The age-at- entiance ( generation cohoit) method provides a more piecuc measutement hy lestnctmg all the deaths to membeis of the coi responding geneiution at usk who have common ehaiactet- isties pertaining to the veui of bntl), period of death, changes m eunnmmeotal exposure, and previous employment exposure as well as changes m medical euic and subsequent levels of employment espenence. ft is e\ ident that au internal control, such as Level 1, applied to the generation cohoit method, does not have the limitations of age at death method and has a f.number of inherent advantages1 ` In this respect, too, follow-up studies on eon- -firmatien of primary causes of death and sup plementary histological examinations when ap plied to the cohoit as a whole, include the sub cohort designated as the internal control This ^overcomes some of the problems previously eviperienced of the inability to apply the same iort of confirmation of diagnosis to the study /and control groups because of size, composition, r;or location of the control group It was noted fiom the data presented that, with the exception of Level V of cumulative ^employment experience, there is a consistent increase in the average annual mortality rates lay the cumulative employment experience in- ccreases. This relationship was more apparent ffor age 25-44 than in other age groups for the ans explained above. Level V was an ex- tfption to the rule. In fact, the mortality rates r. Level V were higher than those for Level 1 jjt^bevel II, but were not higher than that of feyel- IV. This drop of the mortality rate for V as compared to that m Level IV could i due'to one or more of the following reasons, employment experience for Level V differs i that of Level IV by the additional employ ; history during 1955-1964, which repre- `a period with much better environmc"*'-' itrol; those who are classified as Leve1 * ipcohort represent those with belt office employees or sat----- ' ' innituiity picture lot Level V was observed for the ptuotl 1955 to mui-1964 as (.(impart'd to the peiuni of 1950 to mid-1964 lor Level iV as a consequence of the dynamic changes of the cohort * The present study ptovules tmthei confirm.!tion o f the high iisk of cancel ni selected sites in asbestos piodnct vvorkeis and also tunuslies the basis of an association of uuieascd nsk fiom canter with the gradient of emplmnu nt expen- ence (Table 4). As was indicated, tlu ie vsas a consistent mciease in the average nimtuhty iate foi all causes of death m geneia! and specificallv Icn malignant neoplasms taidiovasudai dis eases, and asliestosis m association with ntou* ptolonged emplovment m asbestos uidustrv Tins met eased inoitalitv iate was evidnit fot all cancel in genet a! and spec ificalK foi cancel of lung, bionciuis. and tiachea and digestive or gans. Howcvei, in evaluating malignant neo plasms In dotation of employment, the problem of competing usk still holds a peison who was exposed to asbestos dust could die Irom asbestosis and/or cauliovascular diseases ,uul/or ma lignant neoplasms. Theiefoie, an unpoitant factor which inHu- ciucd the extent of the obsenations iclative to the strength of the association m this study was the question of competitixe risks in the analysis of the causes of death '' The significance of the frequency of asbestosis ns a cause of death, and its occurrence as a secondary cause of death, was noted m our earlier study. Deaths at eai her ages lessen the mimber of sumxors, who may live long enough to meet the requirements of the latent period, to develop lung cancer or mesothelioma Env irormiental exposure and dust concentrations were undoubtedly higher in the earlier years of manufacture and prior to the establishment of the cohort and chrvsotde was used almost exclusively.18 18 Consequently, more workers developed asbestosis more readily and died at an earlier age and this has lessened the extent of the findings relative to malignancy. Undoubtedly, continual long-term observation of the present cohort, with a further extension of the latent period, would be most appropriate, and in particular for the age group 15-24 and 25-44 at entrance to the generation cohort. ~ ' ,.,esent study, there was an unusually high number of malignancies specified on the Jrt''fh certificate as "primary site unknown" 8 i > ' fe. mates employed 2 or more years. "t'- ' 'mte queries, to obtain fur`r'-' histological re- 160 MORTALITY 3N ASBESTOS WORKERS view of these cases This situation was unfortu nate because the resolution of these "unknown" cases might have had some bearing on the obseivations pertaining to cancer of the diges tive system, stomach, colon, and rectum or some other site. In our first study, such a histological review added to the number of lung cancers and detected several mesotheliomas. There were 9 cases of mesothelioma of the peritoneum and pleura, which occurred among 3S1 deaths of the cohort (2.5'?). Hammond et ai. observed 10 mesotheliomas (peritoneum and pleura) among 307 deaths. For malignant neoplasms of the central nervous system, there was 1 subject among the females who died m 1939 and 3 among the males who died between 1940 and mid-1964 There was 1 death due to lymphn- saiconu and 4 deaths due to leukemia observed in the male gioup. Further interpretation of ihese malignant sites was deferred. Of interest, too, was the higher mortality rate than that expected for suicides and accidents and homicides combined There were S deaths due to suicides and 15 deaths due to accidents ami homicides in the total white male eohoit. Ail of the suicides except 1 were employed m the asliestos induct: y tor more than 2 yeais. Useful siipplcinentan epidemiological inhu mation relative to disease patterns can be ob tained In concidning the multiple causes of death and then sequence Foi example, m oui present studs, included m the 142 deaths of the caidim ascnl.il sistum 33D-354 and 400-463) were II subjects in whom asheslosis was indi cated on the death certificate as a sieondare cause of death and 1 with cancel of the large intestine ,is a secondare cause ot death There were* 6 cue s coded pi miai v as toi pulmonale, in 4 at v huh asbestosis was indicated as recoitdure c.tuse of the subjects' death NVe obsened m the fiist studv the contubution d en ied fiom fmther inquire and how the supplementali infoimation would have altered the sequence of coding of the cause of death as lecoided mi the death certificates It was not possible m this extension of urn onginal shk to obtain fiutliei inhumation to amplify adequatek the relationship: between secondare and pi unary causes of death To a certain extent, the problem of multiple causes of death masked the ptopei mteipietation of the eai dim areolar problem obsened m oui asbestos studs. Enlcihne1' Indicated a significantly high moitalits fiom lupcitcnsise Ileatt disease among asbestos products wmkeis as compared to that of United States and ers m other industries. Our findings did ini cardiovascular diseases (excluding vi siOfis affecting the central nervous system), | associated with employment, as was evidfipfc by the consistent increased mortality rate^r more prolonged duration of employment in asbestos industry. The risk of dying fronts diovascular disease was 2.5 times that of'' internal control for age 45-64 (as of 1940). posure to asbestos dust, therefore, might s the cardiovascular system either directly. ( to an unknown mechanism) and/or in (due to cor pulmonale and/or right heart' ure) In the present study, there was a total of deaths in which the primary cause of death was due to asbestosis-31 m males and 8 in females!, These usbestosis deaths, coded as a primary cause of death, provided a higher mortality rate in association with the increased level ot eui-,-.i ployment experience m the asbestos industry. 5 In addition, there were 21 deaths in whichgi asbestosis appeared as a secondary cause of death. As indicated before, there was no at1*? tempt to utilize the secondary cause of death in the analysis of the findings. O'Donnell,''' a pathologist who had initially observed a high association between asbestosis and lung cancer among the employees of this I. plant, has now u*poited--based upon the admis A sions to only 1 of 3 mam hospitals m the comnmmtv area--55 cases of pioved asbestosis with 28 malignant neoplasms 23 bronchogenic and 5 mesotheliomas of the jientoneum and pteurad" Tins is of particular interest to out study be cause of the 23 lung-cancer cases Only 12 em ployees could be identified as being in onr [9)8-19 39 cohort, a significant factor when considered in light of the finding that of the 12 matched deaths of our cohort as compared with O'Doi moll's lung-cancer cases, only 10 were so classified m. om cohort and 2 were classified as deaths from other causes These additional 2 lung-cancer cases had accumulative employ ment evpeueuce of Lee els II and IV, when these are added to the cm responding levels of employment esperience of the cohort, the mort-ditv late shown in Table 4 would be raised cnrrespondmgk and the toU'i W ,g cancers for the white males increased to .*? * r total cohort. This lack of identification : nuc-iii'th of the matched cas t iidence ot the underestimatf 160 MORTALITY JN ASBESTOS WORKERS t view of these cases This situation was unfortu nate because the resolution of these "unknown" cases might have had some bearing on the obseixattons pertaining to cancer of the diges tive system, stomach, colon, and rectum or some other site. In our first study, such a histological review added to the number of lung cancers and detected several mesotheliomas. There were 9 cases of mesothelioma of the peritoneum and pleura, which occurred among 3S1 deaths of the cohort (2.5?). Hammond et ah observed 10 mesotheliomas (peritoneum and pleura) among 307 deaths. For malignant neoplasms of the central nervous system, there was 1 subject among the females who died in 1939 and 3 among the males who died between 1940 and nud-1964 There was 1 death due to lymphnsaicoma and 4 deaths due to leukemia observed m the male gioitp. Further mterpietation of these malignant sites was deferred. Of mteicst. too, was the higher mortality rate than that expected for suicides and accidents and homicides combined There were S deaths due to suicides and 15 deaths due to accidents and homicides m the total white male eolioit. Ail of the suicides except 1 were employed m the asbestos inclustiy tor mine than 2 ycais. Useful supplemental \ epidemiological mfoimation lel.dixe to disease patterns can lie ob tained In consuleimg the multiple causes of death and then setjiieuce Foi example, m out pieseot stmlx, included m the 142 deaths of the c.udioxasciil.ii sxstem i 110-534 and 400-463) were 11 subjects in whom asbestos's was indi cated on the death ceitificate as a stcoudaix cause of death ami 1 with cancel of the large intestine as a secomlaix cause of death Theic weie 6 cus< s coded pi tmai \ as coi pulmonale, in 4 ot w huh asbe.stosis was indicated as secondaix cause of tile su b lets' death U'e obseixed m the fiist stndx the cootubutioo dom ed fiom Outlier mqituv and how the supplementalx mfoiuiation would have altered the sequence of coding of the cause of death as leeouled on the death certificates it was not possible in this extension nf out oiiginal stndx to obtain tmthei information to amplify adequutdx the lelationsliips Isetween sccondaix and pi unary causes of death To a certain extent, t!ie problem of multiple causes of death masked the ptopei mteiptela tion of the caidiox Astidar problem obxerxcd m oui asbestos stndx, Eutciline1' indicated a sigmficantlx high moitalitx fiom tnpei tensee heatt fltsCa-e among asbestos pinOmts wotkeis as compared to that of United States and ers m other industries. Our findings did in cardiovascular diseases (excluding va sions affecting the central nervous system), n associated with employment, as was evid by the consistent increased mortality rate y more prolonged duration of employment in1 asbestos industry. The risk of dying ronv~ tiiovascular disease was 2.5 times that oF internal control for age 45-64 (as of 1940);* posure to asbestos dust, therefore, might a the cardiovascular system either directly. ( to an unknown mechanism) and/or inc (due to cor pulmonale and/or right heart-f tire) In the present study, there was a total of deaths in which the primary cause of death was. due to asbestosis-31 m males and S in females.',. These asbestosis deaths, coded as a primary,cause of death, provided a higher mortality ram' m association with the increased level ot eui-. ployment experience in the asbestos industry. In addition, there were 21 deaths in whichd, asbestosis appeared as a secondary cause ofA death. As indicated before, there was no a t tempt to utilize the secondary cause of death in the analysis of the findings. O'Donnell,t!l a pathologist who had initially ohserxed a high association between asbestosis and lung cancer among the employees of this plant, has now icpoi ted--based upon the admis sions to only I of 3 mam hospitals in the com munity area--55 cases of piox'ed asbestosis with 26 malignant neoplasms 23 bronchogenic and 5 mesotheliomas of the pentoneum and pleura-*0 Th is is of particular interest to om study be cause of the 23 lung-cancer cases Only 12 em ployees could be identified as being in our [938-19 39 cohott. a significant factor when luiisideied in light of the finding that of the 12 matched deaths of our cohort as compared xvith O'Donnell's lung-cancer cases, only 10 xvere so classified in. oni cohoit and 2 were classified as deaths from other causes These additional 2 lung-cancer cases had .iccumulatixe employ ment expellence of Levels II and IV, when these aie added to the cot responding levels of employment experience of the cohort, the mor. t.ibtx late shown in Table 4 would be raised Lorrespondmgk and the tot.:' cancers for the white males increased to total cohort. This lack of irlentificatior nnc-sisth of the matched c t \ idence of the undeiestm . Vol 9 No 4 April 1967 \1A\CIS0 & L'L-Vmn 161 in our cohort, particular!* when it is leulim l that the observations made on the total matched cases (related to one-fourth ot the lung cancels m our asbestos cohoit) constitute admissions to only one of the hospitals. O'Donnell, moreover, reported only cases ot respiratoiv cancer that were associated with asbestosis Although we o b sm ed 9 cases ot mesotheli oma, 1 of the pleura and 8 of die pentomuim, O'Donnell reported 3 additional cases of meso thelioma m employees of the same plant (which workers were not part of our 1938-1939 cohoit) Another death due to mesothelioma of the peritoneum occurred in a foimei employee who was not in our cohoit and uas not in O'Donnells group of cases of mesothelioma This total of 13 cases of mesothelioma (all of employees from a single plant m a small com munity engaged in the manufactm e of the same asbestos products) provides a very strong asso ciation for such a raie disease, in which all ex cept 1 of the 10 mesothelioma of our study weie employed for more than 2 sears In general, the pathological confiimation by O'Donnell of lung cancers and mesothelioma among former employees of the same plant (from which plant our cohort was established, over the same period of time--1940-1965) fur ther substantiates the lelationship of malignan c i e s and asbestos exposure, observed in our co hort study of employees classified by duration of employment. Summary and Conclusions A cohort study of 1265 white males and 228 `.white females who were employed m a plant manufacturing asbestos products m 1938-1939 Lwas established through Social Security records ad observed to mid-1984. The cohort study represents a series of refine- its in methodology pertaining to prospective Spidemiological studies of industrial popula- iris. The Social Security cohort approach has pen developed to include the classification of ^members of a cohort by duration of employ t from 1938 m the plant under study. A thod also is demonstrated of establishing a bmogeneous generation cohort and an internal atrol according to age and specific levels of upioyment experience for a company under iidy, as derived from Social Security. -was observed in this study that when the 1533 i 1- -- considered as individual s, that ihc xov une had a lower mortality expruence than the 1938 one which was prinninh iniltienced )v the years of employment prior to 1918 Further, the 1939 cohort observa tion piovided an indication of the effectiveness of em iionniental changes and control measures m subsequent \ears. For the purposes ot our studs, the combined cohort of 193S-1939 was utili/.ed and the levels of accumulative employ ment experience from 1938 to nml-1964 and were classified as follows Lev el 1. 0,1-2 0 \ ears, Levc! 11,2 I-T 0 years, Level Ui 7 1-12 0 ve.us, Level IV. 12 0 -1 7 0 ycais: ami Lev el V, 17.1 27.5 ycais Ol employees in the 1938 and 1939 cohort that had a cumulative employment experience of 2 u n is oi less chit mg the pet tod oi 1938 to nud-1%4. Level 1 was utilized as an internal um tiol classified by age Tlieie was a total of 330 deaths among the white males and 31 lor the females Among the males tlieie were 35 malignant tumois of the lung and 43 deaths due to respiratory disease, 31 of which vveie due to asbestosis. Among the females, ot the 11 deaths due to malignancies, 6 were due to mulignanev of the lung and all 8 deaths clue to respnatois diseases were due to asbestosis. There were 9 malignant neoplasms of the peritoneum and/or mesothelioma, 8 in the males and 1 m the females Among the 71 malignancies for the white males employed 2 or more years, 8 were specified on the death certificate as "primary site unknown." The relationship of cumulative employment expei tente on the mortality pattern was as sessed foi all causes, all neoplasms, malignant neoplasms ot the digestive organs and peiitoueum, malignant neoplasms ot lung, diseases of cardiovascular system (except vascular le sions affecting central nervous system), and asbestosis There was a consistent met ease in the average mortality rates as the cumulative employment experience increased This was true for each of these categories with the exception of the digestive system, which involved a small er number of cases and analysis could not be made The problem of "competing'' nsks of deaths due to asbestosis, cardiovascular disease and/or malignant neoplasms, and the relationship of primary and secondary causes of death are also discussed. It is concluded that the duration of cumulative employment experience among as bestos workers in the asbestos-products com pany was directly related to a general increased mortality rate for all causes of death and spe- t& m v.i,, i ib I*rw1 cifically (or malignant lar diseases, and asbestosis. . -- . -mi intectuUooal*! C' "ici!J Health, Wien, Sept ^ 6, Wacneh, J, C Epidemiology of diffai _ 11 Addendum hal tumors evidence of an association ffian in South Africa and the United King A few months after the close of the cohort follow-up in mid-1964, It deaths among the xVy Acad Sci 132 575, 1985. 7 Report of the U I C C ( Internal Against Cancer), Working Croup on . 1938-1939 cohort were reported. The causes of Cancer Arch Environ Health 11:221, Jj these t l deaths follow l, lymphosarcoma of the lung, 6. cardiovascular diseases (including 1 case of cerebral embolism), 1, pulmonary fibro sis; 2, asbestosis; and 1, suicide. All of the de 8 CtLSON, J C. Health hazards of asbent Soc Occupat Med 16 62, 1968. 9, Chios', J D. Problems and changing hazards of exposure to asbestw?) Acad S a 132 896, 1965. ,-x.' - v # ceased were employed in the same asbestos 10 Meyers, R J Mortality of workers insured-) 4 plant for more than 7 sears since 1938 OASDt for the year 1955. Social, tin, July 1981 H.E W., Washington, D. Ot ^ A cknow ledgm ent 11 Ciocco. A,, Mancuso, T F., and Thompson, Four years mortality experience of a-s We wish to thank Dr Antonio Ciocco. Pro fessor and Head of the Department of Biosta the United States working population! -/ Public Health 55 587. 1965. Entefline, P Estimation of expected rate* in t tistics. Graduate School of Public Health, Um- veisity of Pittsburgh, for his aduce and encour agement, ('iiiurufij of Pitidjurph Graduate School of Public Health Department of Occupational Health Pittsburgh, Pa 15217 cupotional disease epidemiology Public Hei Rep 79.073. 1964 __ n Doll, R Mortality from /ung cancer in asbestot^f workers Brit } Iruiustr Med 22 81, 1955. 14 Ksox, J. F . Doll, R. S , and Hill, I. D. analysis of changes in incidence of bronchial < noma in textile asbestos factory. .Ann NY Acad! 132 526, 1965 References 1 M w c t s o . T F and f oi j ter E j Methods of 15 Braun-. D C , and Traun, T. D Epidetniologictfc study of lung cancer in asbestos miners. Arch Indi'iur Health 17 634, 1958 sludvmg (lie i(.`latum "I eroplmtneni and Imm- 16 Mascuso T F Discussion of studies. Ann .VY tvun illness vohtiU .mats sis \ mi, r / Fnbfii Hcn/th Actul Sci 32 589, 1965 19 1959 17 Silikoff. I J . Cuuno, | , anti Hammond, C. As 2 \Ji\risii I J" .mil I i i i n m b I Meflimlnlnm bestos esposiiic and neoplasia }AMA 188 22, m hicIunIii.tl lie.itlli studies-- (lie ilciniisii.ipluc. ap- 19 6 1 pin.itii \ if /i I in tuni lim lth 6 515 96? 15 E \t h u i\ e P E Mortality among asbestos prod 1 M vniinii 1 F and Tin i 11 it E f Methmliilmiv ucts nsori.ers m the l tilled States .Ann A'7 Acad in inihtstiial lii'iltli studies-- (lit1 uiluirl appuuUi mill spt-vtal raiuieiiti' l,i -,ii asbfsltiN trini|iaf,v Su l >2 156. 1965 19 O D osntll W H , and M s s s . K H Asbestos; \n h Lm ouii Health h 2in 196] .it evtimstc factor m the pathogenesis of hroncho- 4 Msscimi T I mil F i - A n v i l . A A Dviiaum t'ciiic. carcinoma Amcr f Path 73 610, 1957 lti.mlies in imliiNlit.il cuhoit studies fm/iiitr \ h t l 20 0'()nv\tLL, W M , Mann, R H , and Crosh, Sure >5 1059 1966 f L Asbestos, .in extrinsic factor in the pjlho- " M w i i mi T F null Ei-AirvH A A Evaluation genesis of bronchogenic carcinoma and mesothe ot i ilium studies- />! imlfiNiu.il pnpnl.itiiins Pro- lioma Cancer 19 i 141. 1966 OH \C r F, OF \F.SCUL\PIUS Serpents ucre s.tcietl lo Aesculapius the healer prohablv because of a super stition tint those animals have a lacultv of renewing their south bv a change of skin. The worship of Aesculapius "as introduced into Rome in a time of great sickness, and an eruliassv sent to the temple of Epidaurus to entreat the aid of the god Aesculapius was propitious and on the return of thc.ship accompanied it in the form of a serpent Arriving m the river Tiber the serpent glided from the vessel and took possession of an island in the river, and a temple was there erected to Ins honor Rnlfiiii b \ \fi/tliolo<ij, bv Thomas Bulfineh Thomas V Crowell Comp.im. New York. 1947. p 29S