Document 4JNb3Dapme0ZjVk11qOoLw6rR

s rn 22 Asbestos Exposure and Neoplasia Irving J. Srl'iLoff. MD, Jacob Churg, MD, tuui E, Cuyli-r lluminiiiul, l),Sr. Y,,r;. Building trades insulation workers have idatively light, iiitrrmiucnt, exposure to asbestos. Of 632 insulation workers, who entered'the trade before 1913 ami were traced through 1962, forty-five died of cancer of the hmg or pleura, whereas only 6,6 such deaths were expected. Three of the pleural tumors were mesotheliomas; there was also one peritoneal mesothelio ma. Four mesotheliomas in a total of 233 deaths is an exceedingly high incidence for melt a rare tumor. In addition, an unex pectedly large number of men died of can cer of the stomach, colon, or rectum 129 compared with 9.4 expected). Other can cers were not increased; 20.5 were expected, 21 occurred. Twelve men died of asheslosis. LTHOUGH PULMONARY CARCINOMA had A.been observed in the earliest studies of asbestosis, association between the two conditions was first suggested "by Lynch and Smith in 193-5.' Ad ditional reports of such association followed. Per haps tile most striking data was presented in the annual report of the Chief Inspector of Factoriesof Croat Britain for 195-5.' livery death with usbestosis in the files of the Factory Department, from the first recognition of asbestosis as a disease entity, was studied. Altogether 3G5 such deaths were recorded (1921-1955). .Sixty-five or 17.STM were found to bo accompanied by cancer of the lung or pleura. Doll.' after reviewing the problem and add ing data of his own, c,oncluded..tliat lungcaticei was a specific industrial hazard joHieayilv exposed asbestos \s takers. Nevertheless, some investigators base held that, while these ob'crvations might be sugg'-stive, they did not establish an increased incidence of care:noma of the hmg in pulmonary asbestosi.s, and further, that the association was unproved. The factor of selection svas considered a poten tial weakness in evaluating reports of autopsy series. It "as noted tiiat complicated aud unusual cases would lie more likely to come to autopsy,thus raising die apparent frequency of associat'd hmg neoplasms/ Further, it was argued that au topsy statistics, which dealt with paiticnlar gmops of tlmse who died, do not u-licet total populations of asbestos "inkers/ Additional reservations wonbased on the frequent absence of data regarding J r,,,n {hf Divix.r.n r.f 'I Imr.it .c *. 1 of m*, mil llu* Dt'p<3llii"'id rtf I* tltiili*,y. .'! hiI bnial Hi III ||.(*! a |I||| mi'etim: <! ti Iitl.hiil Mil rniliiit'M'v in<( ihwi.. % ill tin* ctii*%t .mil ll'r Aiuriic.m 1 .nlu ui1 oi f I'f't l*f> `c.t.nn it ** M2th Aitnii.il Mci-tim: iif tl< Aimrti lit M*iliC3( A"uCi.ihrtti, Atl.mfiv Ci<>. NJ. Jun** |7. 1*163. exposure, smoking iiabits, and pcisinia! in: lory, on the size of scries, arid on inadequate ius;o!o:.';'..-l verification in some eases. Within tile last few years a number or additional problems connected with .".s!,es:ns exposing h. 'appeared, making clarificati.ai and icsnluimn of (in- foregoing .statistical i.neert.ii:,:;. a mailer of sider.ible concern. Fiist, tl. iias >-n gie.aly increased use of the various types of a.sbeslu- ' > five-fold increase in world utilization of tin's g: of minerals, from 500,090 tor.. ;.i 2.500,U(,hi tons per year in the last 50 years), a> s'.eil as a erealh creased nuinlier aiul variety of nidust/a! apiiiua- tions of asbestos (over s..e!i u now corded). Second, uspiciou 1ms been gr; wmg ,..... malignancy associated with asbestos ex; ..sure mov include neoplasms other (li.io carcinoma of ' - lung. Thus, significant : -i e.-msb-p I-..is ! >, claimed between ddbi.se i.iewbei.i.m.i c.f the pie- and peritoneum and asbestos exposin''" TIiis communication is com..-rued with mo-s1:- gations undertaken to study the following fm... (11 tile, incidence ol deaths bi.e in pul.v.ouurs .... cinom.i among a group of uo.i.-.-rs exposed to bestos under United -States industrial-eOiiditi-.ns in the past several decades, "2i whetur-r or not such individuals would also be found to h.iv<- increased risk ol other neoplasm.,, ami >} wherin-t such risks woe.Id be p.vs'-ut m an industry .a':: than the asbestos-producing ,,.xhcsi'<s-prnduci> industries, with which most lepoits the p.,-.: have been (tuk ern-d but "-v i, <.! won hi not n essatily represent die most nn ilani is n, . bestos exposure at tins tune Fiutiu-i. a ss.,s im. that study of ,ai iuthistix v.di: ..-.l.esti.- expos.,,i- of limited extent .aid inteo :r. -.vould ;..... v ...: , light oil the potential piubleins ass.oi nitexl ss.t.i minimal exposing to asbestos. Materials ami -Methods Our ,n\ estigatio.-is have I- '-tl com-ioed v.: : j ,322 membeis ol tin- A-.bist-.s \t orke:-: (:a;:,n i the New Yotk mi-.'i.ipiihl.m ai. ... ineiol .. o, New Ymk ! ,.i al 12 Ness.u... I. I.lii al of tn. [uti-iiiateui.d A . ial:"H o! Ih.it ami i':oxr Inso- lalms A* li \li is \\ t ii .<*: v V. (!. 'nil title - . - plies, tiu-se me: ; o.suS.n; . woi kt r \ .tl.-.i. the union is ( n: t.1<*n n\ :n** t 'In- 1 in:'.ill s uoioiis., ;K :ni <: .: -j s flii ui\ *i.a;-,:ai v.'*:in -i ru-ty o>[ uulusx'. .i-.. uciiuii:c siapinuliiin". C.al.i ri "l.iggv;\\ * in Iiiit;:.:i. l!!:es- are ..li-m uated "pipe Cl ... icis," "lie... lutOl'S. ' .a ".isln-sl..-. ss'OI he! in tins - .nt i y. The union is une of flu- < blest m the Coimlfy . 448050 Vol No 1 ASUESTOS EXPOSURE--SELIKOKF ET AL 23 -- flu* Nr" Vork local, ns the "Salamander Associai * ,|(l(l i,i Hnilcr and Pipe Fellers," was the first union 1 nf m^i'l.ition workers in the United States. It nmai- ^ [mat,',i milt otlicr locals as the current Asbestos Win ker-* Union in 1912. The stability nf this union , |I (V |)( i-i i ellccted in the stabilitv-oLits member;i <|,,|i idls "Once a pipgcovcrer. always",a pipecov- ,.rt.r |i.k been of epidemiological importance to ns ) .uni h.i' made this gioup of men particularly sniti ,1,1,. |.,, the study of long-term effects nf as lies in, nib.'l.itioii. Unlike unskilled workers exposed ' >n asbestos inhalation in poorly paid industries, ' tfu'i'i- i' little labor turnover among insulation < wnrkctv Accurate employment records arc mainl i.uned lw the union, which has also been coni ccrm-d uith health problems in the industry. : Tin* trade was badly hit during the depression; ; some mrii had to drop out and very few were added during the 1930's. By the end of 1942 the / iimnn rolls- consisted mainly of men with consid erable '-'pencnce, plus a few who joined in 1910, 1941. and 1912. Between 1946 and 1962 union mi'iiihri ship increased substantially. Sumer of Data.--From union records, a list was prepuied of every individual who was a member of eithei of the metropolitan locals on Dec 31, I1) 12. or who joined between that date and Dec 31, f A 1962. No one was omitted, whatever his subsoi|iirnt work history. Tlie 19-12 list included 632 | m u. 690 men joined after 1942. I Pei-.nti.il data were obtained from union t coords, I ami dm work history of eacli man was detailed, I mi I,idem withdrawal from employment (war scr. t *m-. ether employment, retirement, illness'. Those data gave the baseline for calculation of the onset | and delation of exposure. For members who laid ''hed. records of the: Health and Welfare Fund prosided date and place of death. Copies of death - -rtifk-atc-.s were obtained on all but one of them. Vutnp,y protocols, histological specimens, and hos. pital iccords were obtained and reviewed in those deaths approximately one half, in which the tcr. nimal illness had occurrrd in a hospital. ' Statistical Analysis.--Previous .studies have sug gested tlut neoplasia associated with ashrstn.sis sel dom net urs until 20 years after first esposme to as bestos dust. Therefore, we decided to limit the present analysis to men with such an rxpusiue histerv Our complete records cover all members nf tin- union (including actise ami retired memj I'eis. both dead and alive) during the 20-year I'eiind horn |.m 1. 1913, tluoiigli Dec 31 1962. Ibm.-iir, utd! few exceptions, the only men with a liisini v of 20 years or longer since first exposure aslmstos u ere the. 632 men on the union mils as 'f J.'ji I. 1913. (The exceptions weie a few tneu . * '*n inuied the union after Jan 1, 1913, but who 'id been employed picvmusly a.s .isbest is -.mikcis vKe.v here.) Ot these 632 men, 235 died before Jan 1. 1963. / Ta/jie I.--Man-Years of Experience of 632 A'.L. i;p$ Workers Exposed to AsOcstos Dust 20 Ycars or longer Yc^s JVM *913- 194/ 1952 35-30 .............. 40-44 .............. *5 <9~J"gv_ 950 us 0 730.5 486,5 ""339.r------- nro-- *0 54- ......... 391 5 364 0 59 .......... 337 0 390.0 60 64................ 221 0 341.5 s?j2i.............. 139 0 mo 70-74 ........................ 33 0 ns s 75-79 .............. 31 5 70.0 80 84 .............. 5 5 18 5 854- ............... 35 2Q 195 31957 2.0 791.5 S33T0 308 0 318.0 3<4 0 256.0 137.0 70.5 38 5 60 Totals ...... ..... 1.912.0 2.4 28.0 2.316.S 1962 u.*o ___/O.O 5 S07.5 71.3 S 755 0 280.0 197.S 70 0 73 5 13.5 2,011.Q Of these 632 men, 339 hud been exposed to asbestos dust prior to 1924. In other words. as t.f Jan 1, 1943, 20 years or ionger bad e!a psed sii w: these 339 men were first exposed. The1 rernaiiau.g 293 men readied the 20-years-since-lirst-exposnre point at some time after Jan 1, 1913. and before the end of 1962. The 339 men who were first exposed prior to 1924 were counted in e..cii ci die 20 -. e.irs (or up to the time of death of those who died). The 293 who were first exposed in J92-1 or J.iter ''-ere counted only after they icached the 2i)-yoaix-sincc-first-e.xposuro point (those who died being dropped at the time of death). _ When the statistics_ were completed, we found that we had records covering a total of 6,737.5 man-years of e.vpei ience of men with a history of 20 years or longer since first exposure to asbestos dust. Of the S,737.5 man-years', 1912.0 were i:i the fiveyear period 1913-19-17; 2.-17S.0 were in the peiiod 'i94S-lSo2; 2,336.5 were in (lie period 1955-1957; .aid 2.011.0 ue-io in tiie period 1955-1962. Table 1 shows the age distnhulion of the inan-se.irs in each of these five-year pounds. Table 2 show- (1) the average agc-'pecilic death rales nl all US white males dm ini; r.uji of llu-sc periods, .u:d (2; the average age-specifie death rates Irom cancel of tile lung, pleura, uirdiastiiumi, mid trache.i nmuiig US white males dm mg each period, a-, repnitc-d by the US National Office of Vital Statistics. The man-years \u-i,- thru multiplied by lie: cor responding lepuitcd US death rates to ascertain the cxpccti.rl uumb'-r u| dead-., under die mill hypothesis (hat the death rates of asbestos uon.ers do not cliflcr from death rates of all US while males (both age and date being taken into consid eration). The u siilts are suiuuim i/ed m I aide 3. llc-MlitS Total Deaths --Dm mg ..the -lust live scuts (11/1519-17) only. 2-S. deaths menued among the .-.sb.-sto-. woikcrs, whereas 39.7 dc-atlis v\,mld have ,coined b7ur~tIiei~rgb-?t'>`eific-.Vleatii rates been the s.,hk: a'sTor'air US white, inalcss dining those sears { 1 able 3). It) Other wnni.s, at the stait of the study, lilt,; axbrslox ssoiki-i> bad below average death rates. This is by no means smprising. Indeed, such 06292 448051 24 A.SIU-.ST01) .rOSUKK-M-.UKljri- I'.T U. /.\.*.*A. A;,cii 1 Tabla 2.--Total Deatns and Deaths From Cancer of the lung. Bronchus, Pleura, Mediastinum. and T.achca per 10.000 White >.1aies per Year* 35-39 4044 ..... 45-49 50-54" 35 59 . 50-44 , 45-69 70-74 . 75 79 aoa4 . 85+ . 1943-1947____________ _____________ 1948-1952 Tola! 36 55 94 153 m 795 435 634 9/7 t.453 2.422 Uung Cinetrr 1 2 4 s 7 7 6 6 5 3 Total 30 48 78 124 189 28t 417 60S 915 1.353 3.163 Cong Concert t -3_______ 5 8 10 u 11 10 8 7 19S3-I9S/ Total Z*t 43 -- 115 1/8 276 16 558 3/8 1.3*15 3.01 7 Lon;* Cancerr 1 3 G 10 14 ;; t Ci 14 W 0 1958-1962 Tot.ll ?fi 43 /o . *; is 17a 2/2 41 d 03/ *>G 2 14H C-nf rrf : l 3 / :t ./ ;. : l. Oe.Mh AS reported vuintMily by th US NAOon.it Olfce of Vtf.it SUfisocs A fM/h.yojf is Rivifh h<r* tor* .cn period for 1059 156? $ a protection of 1953-1960. Since 1961*1962 r.tc* ore not yet ovi.ioi. tOeattt rates include cancer of the lung, bronchus, pleura, mediastinum, and tracnea, assigned to international list code No. 47b; ;,fQe to 1949 and to No. 160-L64 thereafter. is almost always foimtl in the first few years of a prospective epidemiological study of this type. The explanation is almost certainly as follows: The 632 men in this analysis were actively employed as as bestos workers in 19-12. Since disability from illness or other causes precludes einployrfveIiT~7n~a*lraclo of this- tvme. tiie.se men were presumablyTwell (or at least not disabled)jit the start pOlib~sftdy pe/iad., Almost any grrmp_so selected -is to exclude thaJlLancl jlisabled lias a lower dcaHi~afe~during the_cn_suing few years tli.ii) doesjlie'general popu lation, since ill and disabled persons have extremeJyjiigir cleatlrrat.es-*" A' selective**effect* of`this* type gradually wears off with time and largely disap pears within five to ten years from the time of in itial selection. During the second five-year period (191S-1932) the death rate of the asbestos workers was slight ly higher than the death rate of all US white males, ie, 54 observed deaths compared with 50.S ex pected deaths. In later periods, the death rate of tho asbestos workers was proportionately higher. For the period'1953-1957, there were 35 observed deaths compared with 5G.fi expected deaths, and for the period 193S-1962, there were -S3 observed deaths compared with only 5-1.4 expected deaths. Table 3.--Observed and Expected Number of Oeaths - . --- - Among 632Asbestos Workers Exposed to- -- - Asbestos Dust 20 Years or Longer Cause of Oeatrt r.m ..... _ ... --/. 19U- 1913. 198 1. 1947 1952 195/ Totot. cause* 23 Observed f isb^stos workers! Cpectcd (US whi* m.iiAsj . . 39.7 54 50 S 85 5tl 6 Tot.il '.VtCl''. *"*H Mt^S OiKefvftf f.'sn^stos workers! fcpcctcd UJS wmij.* m.W-sl Cancer of luru{ .mil ulcii^.i Observed |.ish<*stos Eoectfd (US wh*tc m.ues) 13 5.7 a 08 17 8.1 8 1.4 26 }3 0 13 ro Cancer o stomach, colon a*i ((ctinn 4a ; Observer! (nsh^stos workcrsi C*orct**d tliS white m.ues) z.o 2 S 7 6 Cancer o* all other sites co btn*i 3 5 n Ohservrd <.v;lestos work'S) <eclrct (US white rtulei) 2.9 4 2 h 4 Asbestosis 0l4 Observed (asbestos workers) Tami, 1953. 1913* 1962 1962 Ur-- 25S-* 54 4 203 5 39 95 9.7 ia 36 5 45 ?4 66 u 2.3 29 94 7 21 50 20 5 7 12 Cancer of the l.uug. I'lnrra, and Tracin'-:. In each of the- four fix e-year pt-nnds, far .non.; di-att.s from cancer <>l the lung t.nd pli-ui.t uuu.i'il among.tin: asbestos worker-, ti.an would li.e.......... curred had their death rat'-, from these dis-r.'i-s been the same as for all U.x white males (T:.!u`. !-. Altogether 45 of the 032 ,h-1><- to> -workers cancer of these sites, when a. i-nlv ii.fi Such would he expected from general Vs expe:;-i.w Of these 45 deaths, 42 wen- recorded as chto hronchugenic c.ircinoma and if to iteuplasms d.e pleura. The pleural ucopI.i-.ms .were all recuatuu as mesotheliomas. Thus it was found llut tin- death rale Iroio i.ni cer of llin hionchns ami pleura was fi.-S times as high among these-asbestos workers as in the gen eral US while m.ilo population (both ago and date being taken into ronsiilmntioni. It may he asked whether the high -.lto of long cancel among lhe.se asbestos workers could p-isSiblv be attributed to an unusually huge prnpoi t:;.u of cigarette smokeis -im-mg them. W"i- cannot ..nswer tins (jiicstioii rhri ctly. -.ucn we have t.u: --t been able to a.sceitain the smoking n.duts o: l:.e men wild died. I lusvi.-vi-r, tile tollowm:', pi'-rr:. -il evidence indicate tli.it unusual smoking habit:- c.iiinot account (or the high death rate bom lung can cer among these winkers: __ IVIu-lmvo-dnlci viewcd-320. .of-tlic, 37.7-+ui sis mg., mcmheis of the 19-12 gtouji. Table 4 gives a mii-..mary of tin- smoking habits m tin's group computed with a sample *4 men di.iwn from the gwa-rai population of 1.121 enmities in 25 slates.' Tin- mIon sample is somewhat madi-qnale st.iet: ir dews not include the men who died and (toes not i..clude all of the present living memiieis u.` (inunion Novel tli*-!."---. it shows that a subst.inii :1 proportion of a.sl.'e-.li-s wu.kiT'- never smok' d rettes legulaiiy. (ieitamly tin-Ui2 men m on: analssis of death rales were not all luwxy c.g-n t'<smokets. In the. general male population, hing-c:... cr death rales are about ten times ... nigh ai.i-.g cigarette smokers -is among ooiismokerx; ,md toe 06283 448052 I l-V Vo I l'-1'- v. i AMitslMs IvM'O.sCHK--al-.UK'nj-K KT Al. fable <1.--Smotim? M.itjits of 320 Abestos Workers reposed to Ashestos Oust 20 Years or U.-rv:!r CouiDared Witli Sample of Men From the General Population" N#f Smoked ''"Rijulafly liknlai WdyU. n, 93 ui 20 3 25.5 Central /PpuliU*n, id a 23 ft 37 1 Smoked NoPviepre_,Ciiaisr*'<n Atbetlo* Worktfl, % * ft ft l 10 t It 8 General Population. % ;5 99 10 2 23,9 S*J"*oie o< men from general population as reported by Hammond and Garfmkei 7 lU*tory <tt ~CeeRii'Smo*in A*b*tto% *Workers. t b* l }') c f.9 / 62 7 >'o;?ul.ition, t* ***73/ /J 2 *sl 2 "** V) 0 ~ <Ic.itli into from lung cancer increases greatly with tlu* .uniiiint of cigarette smoking.* However, a large |irnportiii!i of .ill men in tlic United States have a liistnri .if regular cigarette smoking. From data in ,i prospective study on smoking,* it may he esti mated that if all men smoked a pack or more of cigarettes a day (ic, if all the nnnxmokcrs, cigar tmnki-iv. pipe smokers, and light cigarette smok ers had instead, been heavy cigarette smokers) the lung-t.nicer death rate would In* approximately a I linn s as high as it is at this time From this we may conclude that oven if nil our ashestos workers had smoked a pack or more of cigarettes a day (and, indeed, fmm our sample we know they did not), and if exposure to asbestos "ere of no significance, then their lung cancer >th tale would have hern about 3.-1 times as ,h as the rate in the general US male popula tion. Clearly, the smoking habits of the asl>estos workers cannot account for the fact that their long- cancer death rate was C.-S tones as high as that of "bite males in the general population. C/islrninic\tintil Cnitrcr.--Hathor to our mu prise, the deatii late from cancer of the stomach and the death rate from cancer of the colon and rectum "ere higher among the ashestos- workets than "mild he expected from the tales ii-pnilcd for the LS "lute male population, calculated in the same "ay as lor .lung cancer. Twelve deaths hum gastric >w-coned sm-.-o-j '* ; * L- ' s*. *- " < i;,.iii v. ith onlv -J..3 expected. Sesi iitven deaths Jrcnu c.uicer of the colon and rerlnm uceurird among the asbestos workeis, .is cump.ued svitli 5.2 expected Cmirrr uf All Other Silr<i --The I.omliined death rate fnun cancer of all sites other lli.m lung and I'letira. and stomach, colon, and leetmu was not increased. Twenty-one siic'h deaths nci mied among asbestos, si .sA-t.rt, >1 u illvjt)-i tsjR'thd .L/irs/rim. --Of the 255 cleaths. 12 ' -e due to :isli,-.(r,-.|s ( pulmon.u S' i*.s; '.it- . ... a . .. . :. ,. .etis. i:;-' i . A. I.- i n ijl `.I hi '/I / I '.iillllie-ll C II" :i.r*-:ii? (>; f/i< L"'ii- - i1 to i-.ii MiOMia (if - lino- " ' posurjj_to.jts_he.stos .by iu.sulatiuii wniia-i-.. a.s stmiiccl bore, results in a marked increase m die inci dence, of cancer of the* long, approsm,.,:, ,`v six to seven times the expected incidence. A.'iogrtiu'r. -15 (IT.G'i-) of 2)5 men with mure th.ui ,!0 veais elapsed since the onset ol exposure died of cancer of the hmg or pleura. These data do not give the "incidence of cancer of the lung m jsliextnxis." "limy relate t. the spe cific conditions c.i our investigation: to a :;:Oup i.t men with only intermittent exposure to ii-..iti.-ria!': containing limited amounts (often 2r'<- to ju") of asbestos under working conditions v.u\ing fi.im very dusty, as in extracting old insulation in closed quarters, to those.- with little- dust exposure, as in building construction in open air. Moreover, they relate to the relatively recent past, in a trade with the .shorter work week of the .strong building trade-, unions, in an era when industry has been aware of potential asbestos hazard and (lie woikii. . popu lation lias had some consciousness o; potent ini xixk__ Ls-snciated with dust exposure. '! Iiese d.,t.t would nut nci rsx.1tllv apply to .islieslos r .pn-nut: in otiu-r industi k-s. such as the bit any pu.di.eia.a of asbestos products, the asbestos textile u.dustiy. etc. -..here ronditinns t*f cmplu)i.u-i.t in..u ipiito d.iflerent. (ini irsnlls do mil con!;.,,m i t:vc-n liiglier incidence of lung taiie, i ........... . ol be: .. cl.: - t >t{lti\>' ft. ai.il utt! I't ,1 U. \fr.\<tfJtrlit/tn/t. J Vlct iiiitifiir (hr hiv( pleural m i*. i !r. in.s'OCuiilv of i / s InsJolo^K .o v`<*j ifu at inii. 'nine jMti)olo;;is's nili so *, lion ni (iifitiM* ()!i*ihm1 loom/** . otliciN. ;l i\ .1 y }.::* _ln'_dMjpl txh.-. Hirin' 1 hi:*.* j 06284 rM r,* * I ,.i id ujy l 2i Ill1' f't Ji|1 */. M | Th !!!&. \\i f. * t ti 15* * il ?** ~ 448053 ZG A.XIII-.MO.'i i ' rOUiltK-M-.t.lKOi . l.T Al, growing number at reports of individual cases" suggests tli.it (hoc tumors are perhaps becoming relatively Iretpient cnniplic.itiOTu, -of- nshgsttj;. "TX' posure. Our observations in tin's series are similarly stif.'gestive. In tin tv of tlir 'lob deaths among the men who had worked far 20 years o, ..ore, the exam ining pathologist considered the death due to dif fuse plewral mesothelioma, and in the two cases in which wc have been aide to res iew the histological material, the histological appearance was that of ten so categorized, and nshestos bodies were pres ent. This incidence of more than 1% of deaths from, pleural mcsothcliunnijs,strikingly lugli Jor a turner svhich is generally considered to he extreme ly rare. In one case in our scries pathoIogicTil examlnafmn suggested diffuse peritoneal mesotheli oma. This single experience is too fragmentary for evaluation. Gastrointestinal Carcinoma.--Isolated instances of gastrointestinal carcinoma in the presence of asbestosis have been known, but there have been no data to indicate that these were more than coinci dental findings. Among the asbestos workers studied here, cancer of the stomach, colon, and rectum was three times as frerpieut as expected. These data suggest that there may perhaps be an etiological relationship between industrial asbestos exposure and carcinoma of the gastrointestinal tract. Environmental Asbestos Exposure.--The recent demonstration, by South African " and Uritish " in vestigators of pleural and peritoneal neoplasms among individuals who had chance environmental exposure to asbestos many years before raises the very important r|ucstion of possible widespread carcinogenic air pollupon. The possibility of en vironmental exposure has long been known. Soon after the initial clarification of asbestuvts as a clinic entity, Iladdow demonstrated asbestos bodies in a man not employed in the iudustiy lmt living next dfini in an .IsiicsO/s fat 1 * #1 * lias ftiuiite' u.e. i mirrored m the find.tig of , .'aome l.i-i vlluon <.. "Cast: among residents ot a i.immunity near a lieuilimn factors-. 11 What is .iic'ii', however, is an appieCation of the potential extent of the problem. Thomson arid associates " base reported the frer|iicut findings of asbestos h.-dies in the lungs of urban dwellers. Among O'.'il'd individuals x-rayed in .in area about an asbestos mine in Fiol.u.d, fuviluoto 11 found -IT) cases of pleural calciiu .,(iou of the type characteristically seen among asi- sO s workers, without obvious cause, in a coinpar.iMe aica without any asbestos mine, no cases v.eefound among 7,101 persons waved. It should lanoted that these were not people who worked m the mine--none did--but. i at her. were farmers housewives, and othets who "lived in the gc?:al location. In one subject who came to autnpsv. polarized-Iight microscopy demonstrated ash. (il)eis in the hue',. Similarly, the line.; ol i o.-. -.v.i/. ing near the mine also shoved the piescuc.- asbestos. A particular variety of vie mental ex;..".- may he of even greater cun. . . i, A.xh-'-lus ex;-.- ..< in industry will imt he iii.ii.-d to t::c parte id.i. craft that utili/es the maten.il. The iioatim; lii- is do not rC.speCt job classifications. Titus, for e> ample, insulation winkers iiii.mulio-ilb, .shaie d. exposure with thc-ir workmates in ntl-.er tiade... intimate contact with asbestos is ptissilrle for elec tricians, plumbers, slicel-mei.il workers, stcamfilters, laborers, carpenters, I inner maki . .mil fore men: perhaps even the supvi vising aiebituot xbuuld-- be included. 1 K IfiOdi St, Xi-.v Vi.rk lOOg't .Ur. Selik.,f:). "tins' sillily w.ts sii|e'.nO**l f>- tin- iii-.Mlii |U -.t-.iii.a C..,nit- Cll nt (lie Cltv el i^ l".v Vnrk. Oonprraci.u: j:i tin* no... -fff iii.* i v*i.>;.. . ; fitt*rv i*l in:* ............ .d A\...... .. o: H.,: a.v! : IdMll.itnrv and Adrstfs Woim'i\ 7\ .% i.u ni. I ai.-". . ollum.** am! i.iruJirfs'lup nl :ln* ions au** Nrw.ifV., ,N . ItiCills of tltU Cfiiim. Hcfcrcucfi !. LvjkIi, K.M., and Smitli, W.A.: Puimonaiy A*hp*dosis: Carcinoma of -Lnnjj m A.vlteslo-Silicos**, Amor / Cancer 24:oG-04 (M.tv) 19.13. 2. Animal deport f C.liu'f fo'pi,clnt ol {'.utru*s fur Year 195.7, [.oikIoii: Kor Mainly s fit.itiom-ry Office, 19j(i, cmitfl Ji. i> 2PG. A. f3o|). U,,; Nt>it.iltty Krmtt l.ttn" C!m.i in Ast'vMa* WorkiTN, / htdmlr Med 4. nullity, U-, and J.irob. C.: Ni-e 0* '`>rldspiuiUe ul*r tltit laiuut/akrebs Asheslarlu'iler, Dcutsch Med 81:2M 5. IJraun. J?C.t and Trii.m, Ii|itl*'mioliu;ie.il Study tif Iaim: Outer m Ashe'-t**\ Mmets, A.UA Arch lndu\tr Health l7;G:l4-(i53 (J.me) IfJ-a.S. fi. Wanner, J C.. SlejtUJ*. C.A . and Man fund. I* ; Oifimi* Pletir.il McNOtiieiioiii.i ami AsIipnIon l*.\p*'\ur m Xutdi Western Oipt` Province, tint J Indttxtr Mrd I7:2fi0-271, 19G0. 7. Ilanmlciml. K/.,,, autl Cartink.fl, I..: Mni*kmfa* II.tints f Men and Women, J An/ Canter ln\t 27:419-442 /Auk) S. ] t-mmi'`iid, 1*./!, and !l'.*, \t , . -*l .1. Hatf\: Ui'piMt 011 ('fuly.lAiiir Mt.nti.- of Kcl!.iu*-itp r.f 1**7.- 7f<{ Mimu t. [nl.il \l*,ni.il 1/y,, ii It.P'-s lv f .ni'i*, JAMA irs. J3-IJ72 (Mault I-'Jl-Ldoo iNh.rd* 9. Mi. W I--, *'.-id.- 1 1 1... u;-l l.in:*s. ( l\.\po*anr t/ A*.lh-sJms !);.? -111 l / 1 (fl'tii.d ''(0"!: [,* ilias. Hut Med j 2:1 v97 {\<*v .:i= 1' 'i,l 10. UaddiAv. A.C.. m JI**pin Annual '.fitting Jbitis)* "^Mfilual ,Assn* latuiil, M.*iicur.strr, 19-9, l,/*nt.et 11. Cltpsiwr, C- : Clir'nm l>,i:.n. ..;;v (.r.i!*o!i*.;iat{iN ..1 Ui'sideuls of Cjin.nmtuily .V1.1. .....no i`. .1.: i ; Auto|)!iu;(.l Ca t*st Ann Intern .*2, i tJj.S-li; 1 />*> . * * 12- Tlionisrtfi, J.( , K.i*.: iml * 1. 1 C. and V ' ... . H.H.: Ailu'stos as Mo<U*iu L-ibau lia/.ird, S A;r ; 37-.77-RI ;j.m 19) 19:7*1.' 1*1. Kiv,Ihi*;m. H.: 1'1>*i:i 1 l*.*l*.::* 1'- SiJiM tf N<n.-Wi,cu;:ili'nal i\i:>*"':.. Ai.dii-pi...Mtc* \s:a-s- tti>, Acta luniitd iuppl 19 i, ;:p i***^, 1994 06283 448054 0 '^ ^ OIa fo . f-*VV */'* y vV f K / uu~ /`-<^-io'-\+0kdZj _ lLsVu<*.\ do* V- U The New England Journal of Medicine Formerly the Boston Medical and Surgical Journal Established 1828 .r " Published by the Massachusetts Medical Society under the Jurisdiction of The Committee on Publications VOLUME 265 - jULY-DECEMBHl, 1961 8 Fenway, Boston 15 EXHIBIT.A 448055 Vol. Uti.'i Nu. fi MKUtCAI. INTKl.l.ICKNCK IIK.L 1 INCH AND liAVI.I.Y jr i MEDICAL INTELLIGENCE pji;fr; \ vjM(XtcU|; .* r?'V ASQE5TOS>s)n a worker engaged -IN-ADTOMOBILE UNDERCOATING Heinrich G. Urucsch, M.D.,# and Harold Bavley, B.S.. Ct(.E.f BOSTON 'T'HE term pneumoconiosis applies to diseases of A the lungs caused by inhalation of foreign ma terial. A more specific diagnosis will depend upon correct identification of noxious substances in air samples, sputum and, whenever possible, lung tissues. Among the occupational hazards causing penumoco- aiotis.-ashestos nas^becn~icicntilie3~in exposed mine workers, workers handling insulating materials'"corn- [xssed la^dv of asbestos, workers in tire brake-lining industry and workers engaged in asbestos spinning, carding anti weavin^l)Although asbestos bodies Have liccn found in the luma or sputum of patients with no evidence of. pulmonaW disease or heavy exposure,5 presence of asbestos'bodies in the lungs of a ..jrkcr in an occupation hitherto not connected with asbestos makes the folIowing\case worth reporting. J //n-iW'HbV Case Retort IjpeL-* -- F.Tl"j-4l-ygr.oltl automobile mechanic, was utinititeti to a hospital in the vicinity of Boston on December 15, 1958, with an acute febrile disease. He complained of couch, short ness of hreath and yellowish expectoration. He had been well until several weeks previously, when lie had noted the eraduai onset of productive rough, weight loss and excessive fatigue. On admission lie was febrile and couching. The temper ature was moderately elevated. On physical examination there*was. a congenital anomaly of the right arm and "cyanosis of the can." Rales and rhonehi were present over both lungs. There was no clubbing of (he fingers. Laboratory studies showed "yeastlike bodies" in the sputum. Gastric washings were negative for acid-last bacilti. and a Papanico laou smear was negative for malignant rrlls. Blood studies iltowed a hematocrit of 47 per cent, a whitc-crl! count of 10.800. with 72 per cent neutrophils, and a sedimentation rate of 10 mm. per hour. A tentative admission diagnosis of pneumonitis was made. X-ray films taken on (he following day sltowrd tlilfn.se bilateral infiltration of the lungs by minute, discrete nodular densities and rnnsiilerablc accentuation of the peribronchial perivascular markings, particularly of iltc lower lubes. The cardiac contours were not clearly defined, being partially oiitcured by the infiltration. There was considerable bi lateral adenopathy. A bronchoscopy and bronchography performed on De cember 31 showed "tracheobronchitis." Thoracotnmv in ilu- -n of the left lingula on January 5. 1959. revealed that lobes had a fine, granular appearance, suggesting put- `AjumamC nfflfciMir <*t utctliciiw. Tutu Urmmay of Mcdicwc: Hirttci**, Matt*chtotu OtiMrunciii oi Later sii Itefirw* fScmer cwyiwfe MaMdiuactu Deusnirwi't u( Liter ind (mluctrtrt. rnonarv fibrmis. Two wmluc biopsies frntn the lingula auri the lower lobe showed, tnirroscnpically, manv areas of forcien-liodv reaction as well as a few iypir.il asbestos fibers. The foreign-liodv reaction appeared most marked around areas that stained blue anti contained unidontuuinh: homogenous material. Marked connective-tissue rrat nun was tiresent. There as no evidence of cancer, tuberculosis > Bocck's sarcoidosis. The patient made an uneventful recovery, ms fever sub sided and he was discharged on January 9 greatly improvea. He-continued to have some greenish tenacious sputum and slight shortness of breath, with wheeling. He returned to work to the same company and was assigned as a parti distributor in the Service Department. On're-examination he still had a moderate cough, with slight dyspnea on exertion, 12 months later. The occupational.history, revealed that this man was engaged in his present occupation"at the same company as an automobile mechanic for ten years. Previously, he had worked for two years at a sawmanufacturing company, where he operated a cold press, and before this lie had worked at a gasoline sta tion. He had a complete physical examinarion, in cluding a chest film, which was interpreted as nor mal, when he was first hired ten years before ad mission to the hospital. His work consisted of the servicing of new automo biles, essentially from one American car manufac turer. With the exception of fiberglass in small quantities, no material of significance in occupational diseases was used by this worker in his job. In addition, to his routine ..duties for the last ;ix ycats, he Jiad been engaged on a contract, basis in applying, an;asbes.tos-basc underrating on new can. This operation was performed' in a wing of the garage measuring 15 by 26 Qjgi and. closed at both ends by' wide sliding doors;--which permitted the en trance and exit of automobiles. There were large windows at one side of this wing. The undorcoating operation was carried out by means" of a hand-type spray"gun~operated ac a pressure of-110 pounds per square inch and directed against the underside .of ijtc raised..car. .No mechanical ventilation and no respiratory" protective devices were in use during this operation, ^.considerable amount of the tarry asbestos-basc material was dispersed through 'the work .area and onto the worker's clothes and face. The undcrcoating material was pumped from a 55-gailon drum. Each car required approximately + gallons of the material and thirty to sixty minutes of spraying lime. About 1 to 3 cats were sprayed daily by the patient during the (irst five years, and less during the last year. Since the illness suggested the possibility that die undercoating of automobiles was responsible for or contributory to the acute pulmonary' disease, it was deemed advisable to investigate the underrating operation presently performed by many automobile sales and service agencies in Massachusetts. To obtain background information, contact was made with the industrial-hygiene units of the large automobile as- 06237 448056 MO the new KNOT.AND JOURNAL Ot' medicine .\uc. :i. :y>i semblcrs and other state organizations responsible for biic raised bv means of hvdraulic lift. The operator i lie investigation of occupational health hazards. The sprayed the underside of the automobile. The actual rase history was summarized and forwarded to these organizations with a testiest for information regarding whether similar r.ises had been observed in the past. spraying operation required approximately Fifteen to thirty minutes. There was considerable hack qu.nli of the material, striking ail parts of the operatm, N't nit* of these numric-s had knowledge of any similar including the tnec. This contamination resulted in a experiences. The information revealed that in plants reluctance of workers to undertake this work is i outside of Massachusetts, an imtlercoating com|x>nml full-lime occupation and led :o frequent rotation of that contained a rubber or cork base was in use. In workers in this particular job. General means at Massachusetts most of the automobile agencies are ventilation such as a wall fan were provided at a few using an undercoating material that contains asbestos locations. It was noted that no special precautions in an asphalt medium. were taken to' prevent the inhalation of the dispersed The undercoating compounds used by the dealers undercoating coinjxnind. Some of the operators were included in this survey were manufactured by 5 dif provided with plastic face shicids or coated their ferent companies. The material consisted of an as faces with petroleum jelly. phalt base containing approximately 50 per cent of Indtistrial-hvgicnc units that had surveyed the un- asbestos by weight. About 10 per cent of the constit dercoating operations in the past were interested pri uents were fillers sucli as clay. The material was of marily in the solvents used in the undcrcoating ma a mastic consistence, with a petroleum distillate such terial. Their analysis did not reveal any substantial as a high-flash naphtha or kerosene as the solvent. hazard attributable to these solvents. Qur survey was Fifteen different types of American automobiles directed at determining whether asbestos constituted sold and serviced in Metropolitan Boston were se .\_hazard after the prolonged use of certain under- lected for a cross-sectional survey to study the under coating compounds. Atmospheric samples were ->ncoating operation ami its |xHcmial hazards. Fifty- tained during t.iic actual spraying of. the under- five autotnobile sales and service agencies were visited coating material. The average concentrations varied to obtain information on the number of cars under fcom .500,000 to 1,500,000 particles of asbestos per rated annually, the number of employees engaged in cubic foot of air. Microscopical analysis showed 'hit this o|jcraiion, the methods of operation, the protec the asbestos was present in the form of tive equipment worn by the operators and the com tides, less than 10 microns in length. TIie_ position of tiie undercoating compound being utilized. maximum allowable concentration for asbest The survey revealed that the number of cars un- particles less than 10. microns long dispers dereoated by these establishments ranged from as working, atmosphere, as set by the Ame low as 2 to as high as 600 per year. .There was.a-.re?. tercncc of Governmental - Industrial Hygii cent tendency to reduction in the amount of under- 54000,000 partigjfs of.asbcstas per cubic foot of air. coating as compared with previous years, since most The maxinnmwsDlowable concentration for long fibers of the new cars arc delivered undcrcoatcd by the greater than 10 microns in length lias been tentative assemblers. ly set in Massachusetts.^* 1,000.000 fibers per cubic 'flic undcrcoating operation was carried on as a foot of air. The atmospheric contamination due to rule by 1 or 2 employees at the dose of the workday, asbestos in the operations surveyed, based on avaii- -when the o|>craior performed the undcrcoating oper 'able standards, was not excessive. It was noted that ation on his own time, with extra emnfscnsation for each car undcrcoatcd. The location of the ojiciatioiis varied at the diiTcrcnt agencies. In most eases a sec tion of the- garage area was set aside for the o|x:ration, which might be jierfoi tried in an open area or' segregated from the main repair operations by means in some eases the air samples picked up asbestos par ticles surrounded by an asphalt coating. Additional information about the health of ccr-' tain individual operators was obtained. At establish-] men is where at least 150 cars were undcrcoatcd an nually it was recommended that an x-ray film of the chest (14 by 17 inches) lie taken of each employee, of canvas curtains used to prevent the material, during spraying, from lodging on other automobiles in die area. About 25 per cent of the agencies had engaged in this operation. In some establishments arrangements wetc made with die local health units for free x-ray studies; in others, the expenses were separate workrooms used exclusively for this opera underwritten by tnc employer. Twenty-rive of 'he 75- tion. The undcrcoating material was usually re employees involved nad such fiims taken. Ail x-ray ceived in 55-gallon drums and dumped into 275-gal studies were interpreted as negative. .* lon storage tanks. Under a pressure of approximately 100 pounds jicr square inch the mastic material was forced through a spray gun of the type used in spray Discussion painting. Parts of the automobile that were not un- The observations here recorded raise the question; dcrcoated were protected during spraying by mask whether die use of an undcrcoating material contain-- ing tape. The wheels were removed, and the automo- ing asbestos had a direct relation to die clinical and 06238 448057 : -lOGl. ' Voi. ans No. a MKOICAI. tiNTKL.J.1* i-NCB--KKRK.IS KT rtl. hit pcrator anatomic findings. `Hie mairriai that tiic patient workers wu.h pioloitgeu .uid rnuimuous exposure to ' *~Nunl.. used contained asbestos of various (User sires in an tilts operation are made. .r icra(f. :d in ;t a*|ihal> hasp and was hcltl in a inastic form by a sol vent of tltn |x:iiolctmt-disiill:iio ty|x\ Lung biopsy trvcHed tlte presence ok asbestos bodies of character istic npitcarancc. Tlte timtsnal finding in this case . VVc arc indebted to R. F,, I'nrrand. M.D.. uf t'in-hlmri;. lor pt-nm'shm >o report i|,,, i-xsr.aud 'o II. :S(i.irttitr* M.D.. p.iilmlmmi. liiiiuaiiii Hospital. Pin liJi.im, fm k-vivw of the paihoiouirat tixndmmit. k as a tion of was the ptcscncu of numerous amorphous bluishstaining tic|xits fairly widely disponed throughout RefGKeoces ana of c a few autiom the specimen and surrounded hv inilntnmatory and connective-tissue reaction. Tlte x-ray appearance nf finely granular infiltration throughout both lower --t.'J (ii(ttijmj. eri*.. 1m3. Unrtitt l Ottupmlimmi. HUS |>|i. It,mom (.ililc. drawn. . Holt, P. f. PneummcwM: tniiutOinl if tk* kmmt 6r duil. pp. Camioti: Arnold. 1037.. P. 14.5. sperscd lobes and the possibility that the sputum also con -s were i their tained asbestos Ixxlies ("yeastlikc bodies') indicate that the lung .process in this man was of a chronic NEPHROTIC SYNDROME CAUSED BY nature consistent with pneumoconiosis and tlte di PROBENECID* he lin ed pri* ig maitantiai rect local action of foreign material such as asphalt and asbestos. This is also suggested by some of the air tests obtained in the survey. From llie point of view nf occupational health it Thomas F. Ferris, * Walter S. Morcan. M.D..J ano Hoivarij Levitin, M.04 ey was .'titmcd is significant that the patient, in contrast to the workers observed in the survey, had heen daily and NEW HAVF.N. CONNECTICUT underre obundervaried . continuously engaged* in the undcrcoating operation for more than five years, that no history of previous lung disease or cx[xisurrs to noxious material could Ixi demonstrated anti that the survey had shown / I 'HE nephrotic syndrome has been reported to occur in the course of ilu-rapy with itfritumlicr of drttgs including trimitthadionc.1" parnuicthadiorov mercurial diuretics,1 tolliwiamidtr* anti perchlorate,'1 os per :d that that the spraying procedure was accompanied by considerable hack splash into - the Jjrca3ung~*iohe*of as wcil as in association with sensitivity to poison .c par- in the j Cou nts, is ofTaif. ; fibers t|ie worker. 4Ho cross-sectional survey here iqxmcd indicates tliat undcc-ptcvailing' methods of jjperation,..the .use nf_an asbestos-base undcrcoating, when limited to short exposures, has not resulted jn*an ^occupational hazard. ifcwcycr.jf thtsTipcratioti.Ts*performed con tinuously without adequate ventilation anti protccUvc respiratory.equipment it may expose the .worker oak1 and bee sting.* In the case rc|3ortcd below, the nephrotic syn drome appeared to he. the result of a reaction to probenccid.fi Although proteinuria and renal failure 'are known to occur in the course of chronic gout, tiic nephrotic syndrome has not heretofore been reported as a result of gouty nephritis or in association with probenecid therapy, ggr- - ---- tativecubic ie to vailthat par- ccrabiish:d anof die ployce i merits t units i were the 75 x-ray v no mainil and tojhe jwtcntial.dangcr of pneumoconiosis. Cask Report As a proteem c measure, it is thcrcforc'rccoiiimcnd- ! cd that workers using asbestos-hase undcrcoating A 52-ycar-old man was first seetiat the Crate-New Hawn Hospital in January. 1354. hcrause of acute arthritis nf tin* material over a jjerioii of ten hours weekly or more richt tatcc. Pltysiral examination was negative except for tin- for |5criods"iciiger than one year should observe the painful awrllim; of the knee. The blood pressure was 114/35 following-rules: Urinalysis was necative. Tlte nntiprotc'm nitrogen was HR me., the fastine blood iuar 100 me., and the scrum uric acid on 2 occasions 3.0 me. and 9.9 me. per 100 mi. Tlte Pre-employiuent and jieriodic x-ray studies of the acute attack of pout responded in 24 hours without specific .chest, with the use of large-sized films (14 by 17 indies) should lie made. When possible die workers should he rotated. therapy, and he was diseharccd on probenecid. 1 cm. twice a day, and a low-purine diet. Eighteen* .lavs later he exItertettccd urticaria, which subsided when probenecid was discontinued. He was then advised in stop probenecid anti Approved respiratory devices, with additional to take colchicine. 1.2 me. daily, as ;itopli>4nxis acainst piotnction fr the eyes, should lx* worn. further acute ai larks nf emit. fit March. 1954. priilKnircitl. I etu. daily, was restarted. Mechanical ventilation should he provided in the When next seen in May, 1951, th. patient had eainctl 10 immediate vicinity of the work area.. kc. (22 pounds), but no evidence of edema was present. Two weeks later die weicht Had inrrcasetl further, and cross pitting edema was noted. No urinalysis was done at that Summary On the basis nf a clinical and pathological study of a case of pneumoconiosis in a worker engaged * Fmm the 0j***iwtn nf internal Medicine. Yale Unncnuy SelwwW nf Mrtfwtttr. Awtat lie tram* ft**m lic tlmtrri States PtiWSe Health $ef**e* (IM34| 4wi the Cclli fiMmlattmu tVmunt rwdent tit imedicine. Yhle-iV#w ffawrn .Medical Centtt. in the undcrcoating of automobiles with an asbestoshase coni|X)und, a cross-sectional survey of this opera tion in the Commonwealth of Massachusetts was undertaken. Appropriate recommendations to protect tAvtitufU ,eiitieal Mctiieine. imtlieine* Yale SeMooi ol *A<taiit prnlr****r of <tTf<iieine. Ynle SehoAl of Medicine: iiiwititKiif. Atn^rtcjrt Heart Aanicunon. ln tike fittm of Hencrntd. Merck Shan* and Unfcnw, U#t Pornt. Penflnrivceia. 0628? 09 448058