Document RJzjvDwq33MxX4KD1aDw57eo8

FILE NAME: Kent (KNT) DATE: 1955 DOC#: KNT102 DOCUMENT DESCRIPTION: US Dept of Health - A Quest Into the Environmental Causes of Cancer of the Lung ) 'i m 11 ) i 's ; r i i ,\ 111\ i M, ;. \ i 'i N i '. , ' f > . ' ' * j >' 1 i: ; /i L /' I \ A Quest luto The Environmental Causes O Caneca* 01 the* Lmijj P 'i `Kzjttfx- '>*"**} ;; ... ....... i . S. D E P A R T M E N T - i H E A L T H . E D I'C A T IO N ', am W ELFARE J t j C o n lrn is Inimdurtioii l irlirrdl epiili-nuele" ic :i I <mmi-i< |iTil I ions (Vclipil IICIUII evidence mil IvspU'a lel'V cardllcu'cns Kpidcinielcyiral (Ini,-i on larire iinlusi rial lit*Mips ( lean pa l itMill I II"- pirn I(II V c;l IICIM'S ;l 11(1 cil rci lintel is Scopi' cl e iiv ir c n iu c n la i luii"' (-11 nccr ha/auds I'a llcrn mill type" cl rc s p iru icr y <1111-i-r l ia / a r d - ( Irriipaliiuial r c - p in U c r y (iiicci's . _ I'livsicoclieiniral " l a ic c i a 11iiospiieric eai'ciiicccii" and ical disl riliill cii cf cancel's 111 I lie re-pi nil cry I r a d "|/i - llic 1 'pells Inercame clicmicals Nickel ( 'lircmimn Arsenic Iren . I'crvlliuni ( li-panic chemicals , . . . . . . . __ ( 'cnihnst icn and d isl ilia I i<ni p r o d u d s of coal I'dmli'Uiii. shale cil, and nalnral uas ( 'amen and siliccu pelymers V-lli'sleS I -epropyt nil Musiard pas Ihnhcad ivc clicniicals -.mcnls- and rc n clu sicn s 1>*_'i apiiy lopnirra pli- ..... . ..... .. I iUro<lu(`lion Si'iclllilieall\ aeeepl a hle, :l 11\ Ihenry .lioloiry of limi: eaneer musi relleel u halaiiecd. unii eolupelelll aiullysis Ili ili' c[)iIciiii(>1<>u'i<"i1. uhmIiniI. nini i'.\inl evidcnec imiihm1riiiiiu- th I \ pes nini melila! disi rilmi imi of ami <<1111:i<ls knii'VIl ni' sils|ieri rii exoy'elious ayelits il rii in respira lori ni iviniiimii'sis fi ir e nvi r onment al . urrii|)iil iou.'il. ur iihmIimiI reasons. Il is uni v llimuyli siii-li srrul iny Ilini- significant nini wuri 11\v11i11- i11li>itii;iI imi may he olii ni m<1 IIS Ih llir relative l'<il<* wliirli liti* VHI'iiiUS illili\ illuni it-s|>ir:i1111'\- carcinogens h i m ' played ami hit pisi\ iiijr in ilii' |ii'u(liii'iimi ul' luti: eaneer. T h r follow ina: l a d s ami ohservat ions form an imI>oi-i :iigi ami ini curii 1 pari of s u d i au assessment. O n o r a i 1^ | i <I ( ' 111 i o l o i : ' i r a i ( i o n s i f l o r a l i o n s ilelimle. .'imi progressive increase m , of lime eaneer sla rleil in musi .ii/., 11 eounlries iirouml tlie h i m of tlie 'allies 1 . limi is. al a lim e when -iiiokiiie wits siili t luiliii of minor siy- l'i'iilisl ; Berhliueer: (ros/.e, K a lth iu : ..' kim i. T h is rise was firsi clearly ; !i\ p a llt o lo e is is of ( T n l m l K t ir o p e Tifiy l'.l'JD's ih r m i e h a s t u d y of nata eolleeled d u r i li:: lite lil'St tw o ' t in' 'Jilth entury ami w a s suhse- "Mlirnied ami el.ahoriiled upon hy a invest iii'aIions front America ami ' ah mainly used eaneer mortality u records indicate limi litis develop''U marked variations in the lime ' ';tr_' eaneer. in ils relative dee-ree of : '> ut its progression rate for different eoiHiiries. In ( e r ma n y. l'or iit'wreav,. In ih,, ineidenee of lune' 'e-' unirli in Saxony timi ( Vni r al '' ' A- la le is I!).'! I . Fischer re- rait 'er represented 11.d peris in saxony ae-ninst li.li percent 1ormativ. In De nma rk, aecord' '"ti. a rise in Inni: eaneer fre- ii <tmilii fui du ri ni: lite first three -`"ili ci mi try and only became defi11iIe tiller l!i:iu. Similar o b s e rva ti ons is to a late appearance of this Increase were made in Italy. Th e re siill exisl slnkhiy' dill'erenees in l he Iu11e" eaueer mo r ta li t y rales of dill'erent, eounlries and dill'ereiil rejrlons of (he smne c ou n tr y thy'. t. In Knydaiid. for insltuiee. i'.'> |lel'eenI of till ('meets ill males in v o lv e I lie lllllir: I he oorrrspondiiiir lie'ure for N o rw a y is loss I halt ( p e r ro n !. Similar discrepancies exist for hllt<: etltteer morbidity rales for dill'ereitl metropolitan areas in the I 'niled St a te s as well as for their relative progression rales (Ia I>Ie -In A n o t h e r exampl e of Ihe existence of sirikhiy regional vtirialions in lime' ea n e e r freiptetiey is pr e s e n t e d hy l lie remarktiltle dilferenees in Inns: ea ne er mo r t a l i ty rales hot ween m'htiii-iiidiist riali/.t'd ar eas and rural districts. This has heen deniouslrated for Kntrlaml and Whiles ami for the I 'nited States, where lime; eaneer d e a t h r at es were found to he eonsisteully higher in urhaii areas llttin in rural areas (tallies o -7. lifis. :> a nd 4i. Such observations have heen made in Ohio. New Vol k, and ( 'onneelietil ( Ma ne us o . M c F a r land. and Porterfield: Levin. Kraus. ( ioldberir. and (erhardti and were re|)orted from Knjrland and Whiles by Sl ocks: K e mi a wa y a nd Kennnway: Fulton: anil Philipps. Slocks reported the comparative mortality ratios for males in `itii \| "imi:rii|)li \ (l. 1955 1 T a M o 1. Aut l\or Reinhard __ . Puchs. _ W o l f _______ Passler___ _ _ W olf........... . Peril t z ___ . _ Marchesaui _ K ik u th ___ . . Feilchenfeld - - MarclicsanL R edlich_____ Sey fahrt.____ Karrenstein K ik u th _____ Stachelin. _ . B ejach_____ P r o b s t___ . S e v fa h r t____ B r i e s e ______ B ejach_____ B ejach_____ MarchesanL. R a u ________ Berblint5e r __ M a t e r n a ____ Stachclin__ _ P r o b s t______ S e v fa h r t____ A ssm ann___ M a t e r n a ____ Breekw oldt__ R a u ________ B e r b l i n g e r __ P r o b s t. ___ _ M a t e r n a ____ K ik u th _____ MarchesanL _ Staehelin.. _ Lubarsch.. . S e v fa h rt____ B e r b l i n g e r __ M a t e r n a ____ Rrcckwoldt. P r o b s t______ S t a c h c l i n ___ y ni Ir s o f lun^r c a n c e rs in a u to p s y m a te ria l (IV obsl) Period I.iin;; cancers 'M : Xnmbcr of Tulal : Absolute \ : autopsies ;carcinomas ! Xo. j Percent of all Percent^ of all ` autopsies 1852-1900 1852-70 1854-85 1877-84 1881-94 1885-94 1885-97 1887-90 1889-99 1895-1900 1895-1901 1899-1908 1880-190 8, 710 12, 307 4, 172 9, 240 7, 228 870 ................... 1.940 _________ 5, 022 511 7, 790 711 1, 741 159 3. 337 5 a 8 9 16 1. 83 31 9 1. 27 4 10 22 4. 3 27 3. 8 3 1. 88 0 1900-1925 1900-05 1900-00 1900-07 1900-11 1900-11 1904-08 1900-10 1907-1.3 1898-1910 1908-13 1909-12 1906-10 1909-14 1910-14 1912-14 1912 14 1911-15 1914-18 1912-22 1915-17 1914-19 1915-19 1915-19 1910-20 1918-20 1912-23 1910-22 1915-23 1920 21 1919-23 1920-24 1921-23 1920-25 1921-25 1924 2, 002 10, 272 2, 739 12, 971 0, 808 5, 801 4, 754 4, 810 2, 347 800 3, 448 . 1, 007 0, 083 5, 518 3, 280 4, 989 1, 009 3, 330 2, 429 1, 049 0, 359 3, 097 749 490 934 500 715 205 1, 287 092 586 552 303 48 218 389 70 554 580 337 392 94 755 8, 301 287 75 892 502 31 6.3 l. 5. 1 32 3. 42 90 3. 8 12 2. 1 20 2. 79 3 1. 13 0. 88 00 4. 51 33 4. 8 29 4. 95 0 15 2. 7 8 2. 2 1 2.08 11 5. 0 13 3. 34 11. 23 u 5 7. 14 21 3. 7 27 4. 8 # 10 2. 9 24 0. 12 5 5. 31 140 5. 8 10 38 4. 9 458 5. 4 8. 75 24 8. 3 6 8.0 26 2. 7 fi 36 7. 17 .] 5 4. 9 i m m y r i tr<***iy sp * fy> > v o * > * !* sp t l^r- . E n v iro n m en ta l C auses o f Cancer o f the jjl6-49, -it.il deviations from the avora510 mortality ralo sol al 100. as follows: of adjacent towns with over 200.000 occupied (i\irltmics. Loudon, Fast Ham, \\ est. Ham. C r o y d o n .. loti Birmingham. S m e th w ic k , W a lsa ll, West Bromwich.------------------ 13-1 Manchester, Salford. Stockport. ___________ l.y.) Liverpool, Bootle, Birkenhead. W a ll a s e y .._ 102 Leeds. Bradford. Halifax____ . . . . . _______ 132 i^gidd. with 124,000 occupied dwellings. ....... 1 3 ."> tiara.-tie and Gateshead, with 87,000 occupied .lliims----------------------------. . . ------------ . . . 1h y^n.-ae of l>towns, each with 50,000 to 85,000 .xtupivd dwellings....................... ............... ........ 113 Jwn.i ,ileof 3 towns, each with 10.000 to 50.000 cupied dwellings--------------------------------------- 107 tgjtxale of 12 towns, each with 30.000 to pyXXt occupied dwellings----------------------- 101 mree.ne of 13 towns, each with 20.000 to jfl.tXKI occupied d w ellin g s..___ _____________ 100 iKtvxate. of 20 towns, each with less th an JUXX) occupied dwellings. ______ . . . . ______ $<) la Ohio, for t h e y e a r s 1 9 4 7 --51 ( M a n c u s o , .jUFirlnite, a n d P o r t e r f i e l d ) , llie s t a n d a r d i z e d mortality ratios for Inns; cancer mortality of selected sites among wliile males 25-04 years of tire in urban and rural comities wen*: Metropolitan enmities (Si l 'r h a n counties t 7 ) ........... Rural counties (731 ___ The standard mortality ra-lio is Observed deaths 10 0 . Expected deaths The. type of county is defined, according to degree, of urbanization, as follows: Metropoli tan comity--containing cities with 1950 popula tions of 1()(),()()() or more (91 percent urban); urban --"containing cities with 1950 populations of 50,000-100,000 (1)0.2 percent urban); rural-- containing communities with 1950 populations below 50,000 (41.4 percent urban). Ciinven, Kennaway, and Konnaway only recently recorded fresh evidence supporting earlier observations. The new evidence, indi cated the existence of positive correlations between population density in England and Wales and mortality from cancer of the lungs bUr 2. Frequency rates o f lu n g c a n c e r s in a u to p s y m a te r ia l o f G erm a n p a th o lo g ic a l in s t it u t e s , 1906--52 1 Author Cit v Period Percentage of lung cancers amonjr all cancers Sex Male Female f*rtfT-\V#icls____ : F r a n k f u r t . . Us*...... ...... | Goettingen. and Schoe- ! J e n a ______ . iaerr. B e r l i n ___ Dsseldorf. . , fMhtx-V. . . Zwickau... . D resden....... E m n*...... G erm any __ Goettingen - - Berlin_____ - Z w i c k a u _____ jJ a n d Knoll___ St itori r and Schoe- Duesseldorf__ F r a n k f u r t----Je n a _________ S#*ff-W asi*k____ * ................._....... .. and Kin- Frankfurt.. Duesseldorf. Leipzig____ B avaria___ ami Knoll___ Duesseldorf. Je n a _______ Duesseldorf. Frankfurt.. Germ any__ ify Kahlau. 1000 1900-12 1910-14 1013-17 1920-23 1924- 27 1024- 31 1025- 33 1027-31 1027-31 1925- 31 1931- 40 1932 1932- 30 1938 1942-45 1945-48 1945-48 1940-47 1940-48 1948 1951 1952 2 50 2. 2 0. 2 3. 01 12. 9 19. 79 13. 0 !). 83 15. 4 13. 0 12. 28 13. 9 12. 0 21. 80 13. 0 20. 23 13. 0 35. 53 28. 6 1. 0 0. 97 - ---------- -- -- 12. 94 21. 4 2. 38 4. 8 23. 4 5. 4 ' i l f * * ' HTM''h Monograph No. 3 6 , 1 9 5 5 g ^ l^8!s?as?>rs-5e. i,.s alni Iemale-. Mini e n m e r ni ilie 1;ii \ 11\ iiill lini n| li 11;Iii . l'Ilio Iv ImI ini l |- ppii ri *i11 ln 'ii i o 1111>:i ri lilt r e l a l i v e I iiiilt i|(.`;llll r:i I * III 11u l l il l r i l > l n l e s nini ...,llil willi llu* relnl i ve j >111 >11;i I imi i le n s i lv r n i i iiliii'i. W lieren s, in lite l ' n il <<I willl 11 pnpnlill imi nf -In p e ls n n s JM'I* mile, I Inni: ea n eer leni li n eenrs per ,, inlnil'ilunii-, ni KiiLrlnm! illese lie n res -iMllil Mi 7 jiersnlls per M|il;il'r lllile Milli I i mneer i jimiiii per :;.:;dii i n l m l i i i n n i s . Il luis reeen 11\ lieeli n lise r v e il lim i llie lui li; en lieer ili'Mlll l il l e nr w l i il e lililes liv illir ili lile i ln w n l n w n il ri ni n i l 'it Islm i'eli is exeessi vel llijrli l u i e e I In' l ille nr lililes livinr elsew liere In l l i e e i i v. Il is sninew Imi inieertnin w liellier lilis observa) ion ea rrirs llie suine )iiplirilion as llie nlisers nlions mudi' in Oliio am i in Kn^land nini W ales. >neli ali i n i e r p r e la t ion is s n ^ e s t e il 1 l . u i m r a n e e r r ale -- i n u e e m p s i m a t e r i a l ni* x a r i n i i s l i e r t n a i i i n s l i t i i t e s ni* p a i li n l n ^ v In r t i l e p e r i u d IIWr*-192 Peimil Tul al raiHvr-- 1.uni: rairrr> IVrouii il hnm carn-er' anioni! all cncer.- lianue Avente r/ . 'I?l--!)'! in. '.tu ; i.V i:i s:c_> ili... i :i. S i '* ' i -, > 1 .0 0. 2 2. 1 Vi. 0 li. 1) 7. 0 I. !l li. 2 r e s p ir a lo r \ rane r per 100.1)00 Iu te m ule* in 1ite l. n ile il (!.< ) **'"' Hi'iihli Monu^rapli No. 30. 195. 5 te l I 1 s 1. S J. ; /. *5; -. C' , k; .' i , . f.j. ' \k * * ' *1 A * ' l i ' .1. , Mi T a l l i r I. l u r i . l e i i r r ut' i t - | h i u Iu i \ e n n e f . m u i l . u l U . r n l r s p e r UH).Utili p o p u l a t i o n l'or 9 m e I r o p o l i In n r e in m \. i>>:t inni m ; M u rlm lit v f.*iti- l 'i'iinurv -in- a m i ml s |u;i7 Male- 1H 17 l terroni inrroa-o m ar 'email -- m 17 IVrr.-ut itterease P.i: 7 l'uial 111 17 IV ine Hn *nclin> aln i 1u n u : Alterna W w i riralei ):itla> H iri 111 mu 11;f(11 1 ll'IIVi'!1 S a n iM'aiH'M'u l'lucano Pii l'Im riili i ici mil L:ir\ n \ : \ I la ni a New itele,intette' Uinninuliain )cn\ S an l'Vanci'C' i 'tiicau;o Pii filnirutl )et I tili o in. i . n i. :> 0, 1 i . a ni. :i u. 7 I2 n I. I 11. ;i a. 2 i i 2 n 1. .7 ti. 7 1 1 :i ite 1 tei. l _Mt e h IS. '.1 J l . \i 1. J V jii. 1 : j h i. (i t l. h 1 0 l 1 V s 7. li s u fi, 1 r>.s ! IS :\S\) i u IJU 1 1ii i:i 1 MI o'J (ili 1 Mi lll.'i * Mi 1 sj s. 1. n j. s . J. i l. J :i. '.i t. a t. a j. a a . i i. :> h ti i i i i . u l. -1 C. 1 a. li N. 1 S. 1 7. U . . .7 . 7 u. a i. u i i, a . ti s . ti . s . a Ulti ."Il 1. ISO SU ua MIS r.a 12 1 IS iati 7a ami .7(1 mu 2.7 7. U :i. i :i. :> u. (i '.t. s s. s 7. : 7. U . . il : . 7 . \) 1. 1 :P Z. 1 J. 0 s. U 20. S 17. 2 1 1. 0 1 t. s 20. s 1S. 0 17. Il lit. 0 2. (1 7. *1 2. 7 2. U 2. 0 1. U a. 7 1. 1 a. 4 i i \ l it e litri t Ititi t h e u l u l e m u l e mi ni Iil I;m Is il L o llilll itti il IIMtrilli! 1)\ llir'll s k i II r:t Iicit ili'illlt l'iltr ( P i l l i m i . 'PIIis L ili illiTri'Itlrltt Ut i l i l l i c l i e no r nl r.\|)CI'riirr 11n u o t i s i r;i I i i tu- | | H. i| u;(| rul e pi ove vi l>\ m n n y n r e l l p n l iniiitl i-;i fi-i ik ilici is. s u d i ;ts n r s r n i e a l s . ruiil liti1, pe l l'ulrlllu tIrri v a i i v r s . i i ml l'iulidiirl IVi' sili tsl i l l i rr s in l l i r proti llr I Kilt ul' lutili ru lillirolis mt| re s pi ra ln r y riiiircrs. Aii mlilliotiitl rxpivssiui i n i lliis ui'ltim-niriil p i l l i m i ni lini"' r;i n c c r r a i r s i- coni n i n n i in llir IVrelil l'rporl nf | (e\V. u l m lulllltl lini! ll i rsr l'illes U r l i 1 ili) In .70 p r r r r l i l 11iti'l ir r il molli: il Iti usU'iiil p u | i r \ I m i t i r r s u | ||n< M ri rupi ili Imi I nf r 11 isiii i i nr r C o m p a n y l liuti n u m m : m a l i - Imldini: u'rurrill pulirli-., I ,r\v io 11 lui. oli llir ul tiri' Il il l u i . timi 'Urli i l i U r i r u r r s diti imi e \ L l lur l'r m a l e Imldel's ni llir Uni Iy pcs ni pulirirs. [ Ir p u m i rt| uni limi indust ri a i p o l i r y I m l d r r s i,r | ) i ' i ' s r nl , Tur ilio must pari, urlmn wairc t'anuTS md llmir r ami lir s ili llir I nwe r- i ne nni e I t r a r k r l s a n d i u r l u d r a Iu;Ii p r u p u r l i u n ul m r n etiiratred in maiiuiarl iiriuu' . meelmnicnl inti nsir ir s. minili!:, Il'iinspurlaI itili, and |irrs(Uutl servire. In contrasi. llir ut'iirral policvlmlders arr drawn m u s i l e rtiiu mitldlr- miti Idelt er-incorne o'roups l'nuaut'd in imulm/.nrdoiis urrlipal inus. 'l'Im apparent- rausal siilti(icillU'(> nf fi l'pidrmioluLrirnl findm^s lias lircii demonstra l>y severa! invasijrainrs. Apprciable anou uf .-1-bcu/.pyrcne bave lieen tlcnmnstrated Waller ami ( 'ooper ( R. L. ) amunir Ilu- air poli anis uf Knirlisli t ilit's; liv Knlin ami associ.1) in llir pariiciilalc |diasc nf illese almospln i-unsl il ilei11s in Los Angeles, ami in (he cxha fumes uf unsolide ami diesel rumines (tables ami P). Il lias beeil eslimnled fruni tir (dures l>y Blneklork. Kemiaway. Lewis, a l rtpdmrl limi nlmul Hi imr. nf u.-Lbcn/.pyrt T a h le .7. <'.iuirer n f linier antl Inryiix. K urland a \\ iih's 1910--19 (K r n n a w a y a m i K em vaw av) T y | ie ul' rtm tiiu u iil y lam a eau- Larynx ca: f e r ra titi1 cer ratio1 M ales l'e- males Males mFael. ( reat<*r 1a n n lo n . ( 'otinly bomimli 100 100 100 12!) 1:i7 12.7 2 1)t lier uri,-m disi riet s . IliO 1.711 U S Hural d is t r ic t s .................... . aa i s .7 170 1 Xiiinlier ut perstins prutlueiiiK t tienili. K u virou m eivlal ('.avises o f (laiteer o f llie Lui r,blo6. '.-'mt:* lin e r d e a t h ra to* in 2" SI ;i 11*> o l l In* Tnitol M | 0 H> ;1111 f I`MU. r n iilr ' d< a I ii ra Ir * p e r 100.WO Siali' IH Ili Ois 1 Milii^l n a l i / r i ! S i a l i c . ;i,v lu u l ' ii~____ ii .alan d -i,i',.sn-liiiiL't l> \i .nielli - i'.i lliimpsliii'' v Jcrfy. - ,,Y ork.-. .. -i Kanin . x ' S i , 11 llv ] '2- ' 1 1" 0 0 11 7 s " 11 1 s- - S | 10. 2 "<. i 10. 1 It 7 1 1. 0 7. 0 s. 1 7. 1 Siaiiv; il II t'i iit' 11:i 1 i m i n>l r i a li/:i 1 i"h l m i i t .'h i .a i i h t n l tin* Iu n y i n m a l e s a:ed 2.) \ e a r s a n d o \ *r. I , u p l a n d . I02I-S10. I t e p r n d l i e e d b y p e r mi*->iun o f the Ihiti'di l.m |> iic 4 .aurei* ( .im pait'ii. 10 Hi m is ..'.a'.iu .* ...ri. .j.k.- . h. s 10. 0 " 7. i s. 7 <.>. it s, s s. 0 Alii'MMii 111r;i S l a t e * 1010 10 is Actual mortalitypercent of that expectedfromthedistribution of population by age and class of district HMtr 70 70 - 85 - 00- 115 - ISO- l*5up - :!MMlil - - - - .. _ - .. . . ' . ( 'anilina . '. * . Itakola . .. . - 7.1 anilina . * l.Mlltfloll - s . -;iinu- - .. 1. 0 1 o 7i. 1 `2. 0 o i 1. 0 7. o 1. 1 0 i 1. 2 1. 0 o 'rath rati's for ilio \ ear 1010 were laUen from Animi an Catieer Soeiel v. Im 10 10. ( 'aneer Kali'S for rarii State in tin- i nifed S ta h s In' 111''--i1 for the year t'.Hs u ere pl'nihleod h\ 1hr f -:;ti n/Iicc (if Vita! S tatistic- riiitrn* I. O h sersed an d ex p o rted Inn;: e a n e e r d e a th s in u rb an an d rural O h io , 1017--51. ( T . I**. N l a n n i s o ) / ^ ,___ .X , I C co I ' - - n ; . r |11a* <Jy 'ON < i *l*U* 7. l,utij caniT r m u r la lilx rate*. |M*r 1.000 S ir.tih** hy sex. in V uslria. 107 I (lle r h ie h and ^nlmlil) i nminiiml\ (Miai Males "I*.000 1.000.000 ' - J't.OOO 00.000 ` , <i'-r .f A u stria .. 22. 7 i s. 2 is. 1 II). 2 7i0. 0 21 . ii 22. 2 1 7. 2 ,. N o :. o .> 7 Iii`Inill11<l<T nl ( lliin E x h i'U`1 I. 201 72S I, HIT filili- IIfiilili Monograph No. {0, l*).> 1 I . i l i l r 2 . I.-I i m a Irti . m i n i m i ol a r o ll a I i<* l i \ d r n r a llio n s - in l - m i m i l r s i m p l o if iia > o liiir rxltau.sl " t i l \ ;i i'\ ill* (' H ali n ' n o u l i i l i n t i s - p m l s ( k o t i n ) ..... - l ^ rl. I ,( M.i,ll-1 k k k ............................., , , 1 i.,Mil/' tinnii' \ |1t\ IVIIf I'rh/*l!<'*f1M'* Anil ill1111 rfin a <K> 1 ono 1 .ADO Toon 2 .Aim :;.ooo. a .aoo '.'J:. uv.l .`.o r 47 1 in 121 IS JM ;V2A _(H1 1 12 127 2A A ! 2i 22A 01 177 X> 00 10 72 l * 70 i:i sA >0 20 17,4 102 4li >- 41 1 1 17 1 <>nJin111 jr- an* r \ ) n v > ' n I iii imiii, ai 0 load. III!IV lie inhaled Mini r<`t;tilmmI ill I lie lung's from llirsc sources thump ;l lifclilllc Mild llull lliis ipiantity rc|)rcscnis approximately in.(Kill times I he d o s t 1 ( 0 . 4 111i er npra Ills) eM|);llile o f p r u d u e i n p oMlieer ill m i c e u p o n s u l i e n l u i e o u s i n l r o d u e t i o n . II s h o u l d lie e mphas i /. c d ill I his c o n n e d ion lluil T l-bcii/.pyrene is mill one of I lie several eare m o p en ie c h e m i c al s isohiled from mi mospl ier ie pollu ta nts and lluil. therefore. the mcI iim I toliil .ilnounl of il mospl ier i e eareiimpeli s reaehillp I lie limp' is c o n s i d e r a b l y liiplier ( 1"'.mIIs a n d Sieiner: Kotin and assoeialesi. The lien/.pyrene eonlclil of I lie ai r \v;is increased fourlold dnrinp smop days (Waller). Il is d iffic u lt. if no! im p o s s ib le , to rec o n c ile i lie o b v io u s cau sal sip u d ic a u c c of lliis fact mil evidence w ith (lie claim d ia l such regional, an d especially u r b a n - r u r a l, dilferenees in lim p c a n c e r freipieuey are totally acco u n ted for by dilfer c n e e s iii d ie e i p a r e l l e s n i o k iu p b a b i l s of tht iw o p o p u l a t i o n r ro u p s o r m e r e l y r e l le e t locai d is crep an cies in d ie diapiioslic iiciliuen of urbar a n d r u r a l p h y s i c i a n s a n d in d i e a v a i l a b i l i t y ol diapiioslic medical facilities. Such e x p lan a tio n s beco m e even less tenablf m view of die fact that die annual ape-adjusted i n c r e a s e in f r e ip ie u e y of li m p c a n c e r d e a t h s was h i p h e r in I ill 4 dll t h a n in IK51--44 ( t a b l e 10), w h e re a s d ie m a rk e d ly increased e ip a re tte con sum ption ilurinp previous years should have boosted die annual propressiou rate above that seen d u rin p d ie earlier period, it has been sug. rested d .ie k iu l: H am m o n d ) that this pnradqos eal b e h a v io r of propression ra te s is a ttrib u tab le to th e fact th a t m a n y e ip a r e tte 'sm o k e rs did not live loop enoupli to develop a lim p canee because of their precocious d eath from coronary sclerosis, w h ic h also is a s s u m e d to b e elicited id i T a b le 10. A n n u a l a y r - u ilju s lr il in r r r a s r o f fn q u riiry o f lun^i ra itcrr m o r la lily l V m * n i i n c r eca s e I Itit i 4 0 1 10 4 1 - 4 0 1 1 9 3 3 - 4 4 V M aleVaiale.- 1I Inni. ' l'ut lev. 10.5 8. 5 5.: 8. 0 2 .5 21 f a l li r *). m a iri a m o i in l 1 ni anim ali' h \ d r o r a r h o n in 1- m i m i t r s a m p l *s if licvsrl rxliuuM u i 1li varying* (inni a m i rnyim* m o l t i t i o n *|>rc<l a m i " i t l i fu ri i n j r r t un in r H irir iiry (K o tin ) l,Vw,Iui ii dt> jut mi ini Ic 1.>ad ( 'HII1i1n H1 i.niiu 1, 200 1. ino ii ( 'i>non,>>iuii irlt'iiM' 1 1 .ilo i do " i ilo 1 1 ilo 0 ilo . .ilo ! . ilo ` 1 do. .ilo. o ilo b . . . ilo . 1 do. . ..ilo. . . .lo 1(pliant il ie> are rxpres.M'd in /iii. min. a o 1 nno>otml X . - 147 22 2(>7 71) 741 i 177) 1. MIO (10 2. 700 (140 208 0 277 0 MS 27S s.x.x 4 SS 1. 012 (14 ISS 0 177 50 220 7(> 744 447 s 22 440 ISenzpyrrnr 140 105 772 1. 420 S70 0 47 447 142 1. 700 SO 7S 1. 372 082 1. 087 Uenzperviene Anthan-^ threne | -- -------------1 22 42 124 010 1. 205 7!) 10 171 1)30 <170 0 0 308 1. 071 044 0 J 43 * 223 I 472 '# 469 4. 24 197 1 320 I 944 20 s 16 ? 69 \ i 7 } 666 ; ! - 3 1 j Kiivironniciitul Causes o f o m ajori'.' "I lu 102' a r r i i r - m o k n m . COl'diOr ''O' "-id rX"'''Uiv. <UCH `ln . V | . | ; i l |;1 t ' . . . i n n i v c l l l i ' l l l lx i h - p n - e - ,111 o h s e n o i 1. u m i ' h a l l i 2 m 2 I 11 ' ' a h d i l s t i l l i n ' ,111h1i*e H . -s r \ I-.1 ri lu t itn [ Will'd M U r - m i l -.i'll* )ft0- 195: t(' 1( 111" (JIM IM 1lu* ( (.nul tir-. rounU'v 1 rar Aui iM*r Mal, ii'lii; Ir J;i 1n if.il .Nlld- M.-xiran- : '. r-vuy vtiark -r'iiaiiy. v -. - s.-.- . _ IO.': lO.'il 1017 1O.'it) 10 10 lO.'il 1011 107,1 10 10 lo ll ion.'. io.':; 1O.'tii 1O.' .'r 1017 10.01 1017 10.V 1 o.v; 1s.'ii) iso o IODO 1010 1021) 1020 io:i> io:;o 1010 10 10 107)2 lO ls 10 17 1010 1010 1'un Mm H'i 1i imj)I)JV\ l '.c rler ,*| ;) ) . im1>Is(i: r ; .rjj>|c H : 1 ll;:I,H-n McHiirncv ,.*. ii. O ' K ref,l '^rlMTilU ; !IH1 \ *'! `1V S Jf`i ii >r K i w J mT do 111`11-r hi ! 1 Jt'l i m H-!! I -lu 1>rliiv ( in lo in In ln du 1.1*111' 'Ille <i;! Ulinl i Sitili i!' M'Mtn Kuli un *1 !.. H 1 71 1 A1 1A 1 Jd 1 11 1 jd 1 Jd: 1 i:i. A: 1 i1 i il. 7 i1 i1 i 1 A1 1 1A 1 *. 'i 1 i. s 1 ;. i 1 A. *N 1 s1 11 M1 s1 .'ill 1 10 1 7. 1 livilm in Id's A 11lit 'lr ' . I-I21I I r l 11 1liro l'S i m i m a s |i o l i a p s m u n i i M a r i i s - a l i - l ' s I i r p i u l a r i HI 1" i - i d 1111- r'<ri li-e ( j! , it 11( tol |u } ; Il r a II IH i 1i r 1a ki n --f i n i n -1 \ 11\ a n s i m e ss In l , a - Mli \ c o l II j M' ( r i i c r III 1I l f -1 III s ul a r l r n o - lei'u -i- 1i lll'|)!'l h i - r r m a r k a l l e . I i m r e u v e -, l i m i a f l i T a n i n s i d i o a d i r m r r r , l - r ill III! 1" r a n r r r 1i v i 1u n n S III Ivi -.-ni i il t - r n ed 11(Il'1112 l i l e lil'- l d r e a d e I I I l i l i s r i III III } . 111is 111' S l'Io pi 11el 11 s , . | . | i i . lti. l i a v r r u l l i ' 1 i a In d i il u r i t i " ' re c e n t a c r i i n 111 2 I n A II l i l i i f n ' S f r i 11al h v L i r k i l i l ), ( ' m i s i liTIUU' 11 r r i ' i ' i i r d r d - i r i k i n u l . s il m r i i l a r r p i d e i n i u l n o i r a l l i d i a s ini' n i lim o ' i o i no o* in d i l l - i'l 'i 'l il c u III 1l ' i r s . -i a 1r s . p r o s H i r e s , r u m m m i i l ic s . a m i |in | n i a l u m T* 11J il - u l i s i u i i - i l a l 1h i p a l I r i n - r a l ' r r l \ r u l T r - j h Hit - s v i l i i i h r la 1l e n i (il'rsi'lll i d In II r tlt'n rrr an d sp read u l i h r l ' i r ' a r r l li - n i u k i n " l i i h i l . f i h r a r i i m i (i! r i 1- \ i i ' n i i i i i i n i a l r a n m o u r n s 1111n r l l i a n i l l u s i 1 p u s - - ib is f i l i l i : H ill'll il r i n a r r i I r - i i i o k r - h m i l d m a i n l s a r i ' i n i i i l l u r 1h r r n i i a r k a l i c i n c r e a s e in l l l l r u r a ill'l'l' l'io p I r tir a n d l'or d i e c a u s a i im i ul a m a j o r i >.>rl u n i n l i m o r a n r r l ' s . n i d l l s l l ;a l a l n i 111( 111-1 l'S - i r l a 1r i 1 r a r r i i i u r r n - ss i itili u r l i lil l l n - p a l i c r i i - l l i r r 1In u r o ss i l i u l i i n l i i - l r i a l c s a l . l i - h - m e n i- :lini fili- ll- r III till or p m d u r i s in i h r r i a ti a il i n c l i f e ni' 1i 11e r r i 11 r u l l i l i l'ic s h a v e i r r e a l I s l a r k e d i Il II li Molili \ in l i m e . 1s p r a n d r.\ r u 1. T liis r u h r r p l receives s ip p u rl Irn m a r ri t- ir a i l'Vii l i i a i i u i i il lit e d a l ; m i i h r -r.\ d is i i'i- Im i mu n i lim o 1 a lir r r s . lin e h a n p s in ih e se\ r a l in d u rin o ' ree oil d e c a d e a m i l l i e p r u l i a h l e H 1- i l l n l r i ' l \ in o a l l e a s t a p a r i u l 1In s e p h e - liu m r ii;i ' t a l l i r - I l a n d l'_ l ' m i s i d e i i 112 1lu* r c m a r U i 1i l r s a n a l i i m - ss lii e h i l m m a l i - f e m a l e r a i i n n 111112 r H i r e r s l i a s - h u s s i i a l i ill e r e n ! T a l l i r 12. M a l r - l r t l t a l r - c \ r 1 1io ni* l u n t n r r i ' s i n 1i r i i n a i i N . lfMh-1927 a m i l<)ll)-7() 1s s ii 1027 l '.MO All <'ji v Am In n' l; Hin 1'i \ A il lati Kai in .'.C . 'ti.ii.i ' i . . Wttlf Srviaiol, Seim Hiir-r Wahl Hcjarh I lauf linlUrh Kit'liencn Hai a la I I'."fit i-ut-ii- Hil/ Kikut li r. : 2. 7 2. U ; 2. :> 2. 'I I. t I. .* vo I. s 1ir c - i h 111 1.1'1j i/.iu i|n /.\\ ic kan 1'.i i Ini l 'itl-ilaui Kuril, M lli'hf'lli'll liti du .1flu 1la m i ni rii 1. i r k 1111 K n<ut M.-rk.-I i r ri tr id TU ( 1nillilM IH i 1>IV\ ri' Aiuickcr K :i in /.-rii Kivy Kuni/rn L t d , Ai- 17: 1 11:1 i Ti ; 1 7: 1 0: 1 10: 1 21 : 1 7: 1 IN: 1 21: 1 1 0 :0 12: 1 i'ublif llcaltli Monograph No- 3 0 . 10.*. 9 limes, in ilill'ereul Idealities, mil in dill'ereiil demographic <^roups. ii is mosl unlikely llml siieli discrepancies ami changes an 1attributable lo fluctuations in the intensity of one single factor, such as eigarol te smoking. Instead, they appear to lie due to alterations in the type and extent of the action of a hroad spectrum of en vironmental respiratory earrinogeiis ali'i'cI iiir (In' members of the two sexes to different degrees. The marked and growing ])redominance of males among lung cancer victims seems to be dm1largely to the followin'; factors: 1. Males arc more extensively employed than females in occupations which produce and use known or suspected atmospheric carcinogens. Also, males work more consistently and over longer periods of their lives in such occupations. 2. Males predominate in outdoor occupa tions, ('specially in urban areas, where they be come exposed to carcinogenic pollutants in the general atmosphere (eHluenls of domestic and industrial furnaces, exhaust from gasoline and diesel engines, lust, from rubber tires and from asphalted and oiled roads). 3. Males more often than females perform heavy physical labor requiring deep and fre quent respiratory movements facilitating the penetration of carcinogenic air pollutants into the distal portions of the. respiratory tract, thereby increasing the frequency and degree of exposure. 4. Mali's more often than females work through the entire span of their occupational life within urban areas with proved carcino genic atmospheric pollution, while females st for larger portions of (heir lives in the clear suburban dormitory communities. These considerations provide substantial su port to the concept that local differences general and occupational industrial air poll Iants may more plausibly account for an a preciablc portion of the observed differences attack rates for the two sexes rather than . local variations in their smoking habits. d'ho doubts as to the unrestricted validit of the cigarette theory are deepened if critid ('valuation is made of another dubious link| the chain of claims advanced to bolster ttt concept. It has been maintained (Grahar that squamous cell carcinomas of the bronc mucosa are a specific response to ciga smoking since () this histological type of br chogenio carcinoma was allegedly rare 1920; (6) it has increased considerably sh that date in relative frequency in compa~ to other histological types of carcinoma, peeially adenocarcinoma; and (c) it is more of found in males than in females. The facts are as follows: Bronchioge squamous cell carcinoma has commonly b found with all known occupational respira cancers (table 13). However, many of agents have also elicited other types of p monnrv carcinomas, such as undifferentia round cell carcinomas and adenocarcino Thus, there is no evidence supporting the that any specific respiratory carcinogen eli a specific, and characteristic type of cancer, study of lung cancer records of cases obse T a lilc 13. Ilislu lo g ir a l ty p e s <>f iie e ii|> a lio n a l r esp iratory c a n c e r s, a c c o r d in g lo c a r c in o g e n ic agen t Agent Organ hqiiamou.s cell carci noma with or without cornifica- lion R ou nd cell or oat cell carcinoma Anaplastic or polymor phic carci noma Adeno cinom* ' T a r fum es____________ . . . . . . L u n g ___ 3 i___ . ___ Nickel____ _______ _______ __ . .d o . C h ro m iu m . . . _ _________ . . _do. 1 :____________ 3 : > A sb c sto s.. . . ____ . . . . . . __ do. 111 2 2 R adioactive gases and d u s t . _j . . d o __ ________ ______ 14 J 9 7 3 !____________ 6 Radioactive gases a n d d u s t . . . __ . . d o . . __________ _____ - 3 1 Isopropyl oil_____ _____ . . 1_____d o . _________ _____ 4 10 E nviron m en tal Causes o f Cancer o f the before 1920. or even before 1900, readily estab lishes (lie fael. llinl during those years squamous cell carcinomas of (he bronchi were by no means ran* occurrences (Wolf, l,X9.r) --X squamous cell TabU- 11. ('.o tisiim p lim i o f to b a c c o in p o u n d s |*cr licail-vcar. New /ca la m i am i l niled K ingdom . 1900-1950 (Eastern t) Year i non _ lino. J 920. 1930. 1940. 1950. Pounds of l obacco per head-vear Xew Zealand I'niled Kingdom 2. 3 2. 09 3. 59 : 3. 28 3. 87 1 5. 30 1. 95 2. 22 2. 99 3. 31 3. 97 4. 22 eareinomas among 15 lung cancers- p 11)27 -25 percent squamous cell carcinomas^ tween 1905 and 1918; Watsuji, 1903--23pfr( squamous cell carcinomas between 1 Q2 1X99; Adler, 1912--approximately 40 p0f J squamous coll carcinomas among 181 lu n p ^ j cinemas collected from the literature with ** quatc, histological data; Froc. F'irst Nat Ca l Conf., 1949--44 percent squamous cell nomas in males; 11 percent in females. * While adenocarcinomas arc more frequem' females than in males, they also are more fayl qnenf in voting persons than in old ones (Lini^J skog; Froc. First National Cancer Conf., 194}t t The evidence on hand scarcely supports t | contention that adenocarcinomas are of ciuWl (-nous causation (Lichiut) or that they have**! Lioloirv differing from that of squamous carcinomas (Krcyherg). The male-female q l T a h ir 15. A verage d e a th r a te per y ear per m illio n p e r so n s (m a le s ) from c a n c e r o f th e lun g, 19SJ-S ] N ew Z ealand com pared w ith Knglum l an d W ales (Euslc<>tl) 50C 40C 30C 0C IOC Age Period Country i ; 35-44 45-54 1932-30. ____________ J Xew Z ealan d .................__ __________ 1937-41. ____________ J ____ d o.......... ........................ 1940-41______________ . E ngland an d W a le s . ___ i ................... . . i _______ ; 1 i3 j 87 33 i 108 120 | 424 ( 55-64 65-74 : 1 I : vw 'M | i-- --- * 2 ritio 1 158 | 204 M : living 235 ! 283 802 | 715 a i l 2.5:1 1 not si 1942-40___________. . . . __________ 1942-40______________ -i E ngland an d W ales__ . 40 108 466 i 635 ! s i bomu 132 i 406 1, 072 i 1,032 a ] Ttroni 1947-51___ . ....... ......... _1 Xew Z ea la n d ____ ............... . . . 1 9 4 7 -5 1 _______________ . 1 England a n d Wales . . . _____ ________ 43 287 732 ! 1,014 s ] rondii 100 l 781 1, 682 | 1,857 j 1,9;] 7 Tin 1 9 5 2 -5 3 _______________ .; Xew Z e a la n d _____ __ ______________ 195 2 -5 3 ____ __________ ..1 England a n d W a l e s ... _. . . ________ 01 ! 305 1, 027 1 1, 456 1 I. DM ; the b 175 858 2, 171 2, 650 ; ` I .. cigarc f wnce [' genic Table 16. Observed and expected m ortality from cancer o f the lung according New Zealand or tin *lu lle d K ingdom (K asteott) to place of birtlkt] I with ntiogi Age at entry to United Kingdom Fin not e Place of birth Observed Expected 1 deaths ; deaths Under 30 30 and over per c; count Observed I Expected Observed j Expected ] death deaths deaths deaths death* (fig. 5 lung Xo\v Z ealan d ____ United Kingdom. 032 : 309 ; 721. 8 _ 279. 9 i 201 ! 229. 2 the l' 108 "lJM j JO p X ote: T h e significance of 1hc difference between observed a n d expected d eath s in th e two countries is pCO.OOU] .A Atnet nifico 12 E n v iro n m en ta l C auses o f Cancer o f the NUI. -; f ' jft F i g u r e (> T r e m l s i n m ' U c Um! e m i r o m n e i i l n l f a c t o r s , C n i l e i l S l a t e s . IWJO-- ( I l a n i m u m l ) . of lung cancer (1:0.7) among Mexicans ; in Los Angeles, as well as the ratio of for asbestosis cancers (Merewethor), do upporfc the. view that women have any onal protection against the action of onmental respiratory carcinogens if identical itions of exposure prevail. ie claim that squamous cell carcinoma of tfonchi is in any specific way related to ette smoking thus may be laid to rest, no special histological type of bronehioicarcinoma bears any consistent connection any of the recognized respiratory car gos. nidly, it may be mentioned that there does mat any parallelism between the annual capita consumption of tobacco in different itries and their respective pulmonary cancer li,rates (Iicrbich and Neubold; Gilliam) 5). It has been calculated that the English Ifdanccr rate is apparently double that of Doited States, although the English smoke Percent fewer cigarettes per capita than **Cans. This interesting and perhaps sig|0t observation, which fails to support the validity of the cigarette theory, is disposed of by its proponents hv assuming that exposure to cigarette tar is less severe for Americans who do not smoko cigarettes to the very end than for English smokers who, for economic reasons, indulge in this questionable habit. Recent epidemiological studies of Eastcott in New Zealand provided the most important data on this point. It was found that the relative consumption of tobacco in pounds per head-year for the population of New Zealand and the United Kingdom revealed an inverse relation to their lung cancer deatli rates (tables 14 and 15). Eastcott, moreover, found when comparing the observed number of lung cancer deaths with the expected number for native New Zealanders of British extraction and for immigrants from the United Kingdom that the immigrant group meets with a much higher incidence of broncho genic cancer than would be expected on the basis of equity, suggesting that the immigrant has an increased susceptibility to lung cancer (table 16). The chances of dying of cancer of the lung arc 30 percent higher for all United Kingdom IcBeallli Monograph No. 36, 1955 13 ^ 8 1 0 8 --55----- 3 immigrants, hut for those who were 30 years of aye or more on entering New Zealand, the risk i' To percent higher, according to Easteott. Did'erenees in luihits of tobacco smoking are unlikely lo contribute to this picture, in the opinion of Easteott. Ilerhich and Noubold pointed out that there did not exist any consistent proportional fre quency between cigarette consumption and lung cancer mortality for Upper Austria Kacrnten, on the one side, and for Steien and Tyrol, on the other side, although i four provinces there prevailed approxirru th e same per capita consumption of cigare These authors suggested that the high cancer mortality among the people living ir marginal reg io n s of the northern slope of Alps might be related to climatic-atmospl fig u r e Kim* in a n n u a l p r o d u ctio n or c o n su m p tio n o f c u n c e r-rcla tcd in d u str ia l c h e m ic a ls b etw een an d 1948. PRODUCT UNIT l. BITUMINUS CO AL-PRO D U CTIO N IN U .S ., 2. F U E L MILLIONS OF NET TONS B R IQ U ETS-TO TA L PRODUCTION. THOUSANDS OF N ET TONS 3. CARBON B LA C K - PRODUCTION. IN MILLIONS OF POUNDS 4 . PETROLEUM - PRODUCTION OF CRUDE P ETR O LEU M , MILLIONS OF BA RRELS 5. PETRO LEU M , A S P H A LT -PR O D U CTIO N OF ASPH ALT (FROM P ETR O LEU M ), THOUSANDS OF SHORT TONS U,lsL`-ia ni ^tei('niUlrt. ouBh in aft ,roxin)j||,,jv f cignr..||,; . Wgli l.,,,r lving in ih. loPe of i|,,, itinospl,,.^ >etwon, !.#,, Jitions and to tin* direction of prevailing ^ which bring Ihe industrially polluted ^ 0[ Vienna into the valleys of (ho northern Vlpiac regions. ` ^,uilar observations on the inlluenee of the -roviulin? winds upon the relative frequency of yj11(r cancel's in different areas of the English ; MJ lan(ls were reported by Stocks. Ilerbieh ifid Neubold, moreover, found that the lung ft,r mortality rates were twice as high in omiiuinilies located along main highways, ,vrc the atmosphere was polluted with exhaust from gasoliiu- and diesel motors and the /..i and fumes of asphalted roads, than among >,. inhabitants of villages and towns situated ,,unto from such traffic arteries. In fact, the , in lung cancers follows more closely the remise in consumption of motor fuel and the | ,,-.miction of asphalted highways than the consumption of cigarettes (fig. 0, Hammond; fig. 7, Hneper) and is similar to the increase in production of other cancer-related chemicals. It is apparent from the numerous observa tions and facts of general environmental nature cited that there exists an impressive amount of circumstantial evidence of different character and from various sources which strongly sug gests that several, if not many, environmental factors acting in varying degrees and combina tions cause or contribute to the development of pulmonary cancers and are involved in their recent rise in frequency. Much of the evidence on hand, particularly the irregular epidemio logical pattern of lung cancer, points to an important role which industry-related factors and the growth of modern industry may have assumed in these respects. Occupational Evidence and Respiratory Carcinogens Theconcept that environmental factors cause '(contribute to pulmonary cancers is supported w qmlemiological. medical, and experimental li'iu'c obtained from analysis of lung cancer me*of various occupational population groups u well ns by studies of lung cancers and their ami different causal agents present in a /Tiber of restricted worker groups and in il-delined industrial operations. ffilfiniological D ata on Large Wustrial Groups kpidemiological studies on the frequency of ***cancer among members of large industrial pwjps and trades have brought to light the miuetice of marked variations in the liability ** P^f^ons engaged in different occupations to of U1C lung. Tables 17-19 supply r-iing illustrations of these differences and ** *oine of the factors which may possibly bo i '"V'osihlp for them. S Tlile 17, which lists lung cancer death rates b neveu industrial groups in Ohio, shows a ,,f the I** Ntb- Hr*hli Monograph No. 36, 1955 striking difference between the rates for agri cultural laborers and for employees in the nonferrous metal industry, with rates for trans portation workers occupying a position directly behind the rates for nonferrous metal workers. It seems to he characteristic of inhabitants of agricultural areas to rank first in death rates from cutaneous cancer and last in rates for pulmonary cancer. This is in accordance with the relationship between solar radiation and T abic 17. L un g can cer d ea th rates per 1,000 d ea th s from all causes for 7 ind ustrial groups in O hio, 5,309 m a les, 1947 (M ancuso) Industry Death rate N onferrous m e ta l_____________ - - _______ T r a n s p o r ta t io n __ __ _________ - _________ R ubber an d plastics________________________ Iron an d s t e e l __________________________ Mining a n d q u a r r y in g ............................................j A griculture________________________________ | Slone, clay, glass___________________________j Total---- ------ ------------------------- j I 3. 22 2. 91 2. 34 2. 18 I. 53 .82 . 66 1. 76 15 skin ('nicer and I lie relat ionsliip between low concentrations of carcinogenic air pollulunls and lung cancer. Xonferrous metal workers, on the other hand, often have contact with dust, fumes, and vapors of some carcinogenic metals, such as chromium and nickel, or with arsenicals which are impur ities in many nonforrous metals (copper, zinc, silver). Transportation workers are exposed to the exhaust from gasoline and diesel engines, petroleum lubricants, and dust from asphalted roads. The relatively high death rates of workers employed in the rubber and plastics industry may possibly he attributable to the use of coal far, petroleum oils, and tars, furnace black, mineral pigments of carcinogenic chemi cals, and aromatic amino-antioxidants used in the production of rubber and plastics. The, actual discrepancy in the lung cancer liability between operating and nonoperating railroad workers is even greater than is appar ent. from the figures listed in table 18. ' employment ratio of operating to nonoperai railroad workers in one of two large railr companies was 1:4. From this ratio, it app< that, on the basis of flic crude, nonstanda ized (sex, age) figures presented, about 75 j cent of the lung cancers in railroad employ occurred among the operating group, wh supplied only 25 percent of the total numbei employees. Operating railroad workers eluded engineers, firemen, brakemen, cond tors, switchmen, and roundhouse persom that is, workers exposed to the inhalation of c soot and oil fumes from diesel engines and ft and lubricating oils, which contain carcinogei polycyclic hydrocarbons. Dunncr and Hicks recently called attenti to two additional worker groups, boiler raalt and grain dockers. In the experience Dunncr and Hicks, these workers showed i excessive liability to cancer of the lung. Twe Table lit. I'rcqtirncy o f iiiii cancer a m o n g op eratin g anil n on op eratin g railroad workers j Railroad Period i 'Total lung cancers Type of railroad worker i Operating Number l Percent Nonoperating ' ... ' _ Number Percent Undetermined- -3 ! - i j Number A. 1010-50 I 29 24 ! 83 5 1939-49 ! 104 39 57 15 T able 19. O ceiip alional groups w ith excessive in cid en ce o f lu n g cancer Occupational group Potential respiratory carcinogens Investigator Meta! workers, welders, metal grind ers and polishers, wire makers, tool and die makers, foundry workers, metal moulders, lathe workers, etc. Cigar manufacturers and tobacco nists. Engineers, mechanics, machinists, plumbers, crane operators in smelt ers, etc. Painters, d eco rato rs__________ ______ T ar workers, road workers, asphalters, pavionrs, stokers, patent fuel workers, furnace men, foundry laborers, rollers, etc. Metal du st, lubricating oil m is t___ Tobacco dnst, insecticides, s o o t___ Metal dust, soot, lubricating oil__ Metal pigments, coal tar dyes, carbon black, asphalt paints, solvents, vehicles (lacquers, res ins, synthetic plastics). Tar and pitch fumes and dust, soot. Kennaway and Kennaway; Tu and Grace; Mller; Dublin Vane; Wyndcr and Graham; Laughlin; Breslow a n d associa Seyfarth; Kennaway and Kcnna Enger; Vcrsluvs; Brinkmann. B E C C 1 1944 an d 1952; Gille Turner and Grace; Mller; Wj~ and Graham. B EC C ` 1944; Mller; Dublin Vane; Fulton; Wynder and ham. Kennaway and Kennaway; Ful BECC* 1952; Registrar-Ge~ (1938); McLaughlin. 1 Report of the British Empire Cancer Campaign. 16 Environm ental Causes o f Cancer o f the L i g u r e II. ORE SMELTING CHROME PLATING PIGM ENTS, PAINTS INK, PRINTING ABRASIVE ORE REFINING PLATING CHROMATE BUFFING N ICKEL CARBONYL SMELTING 'MINING ARSEN IC PESTICIDES p h a r m a c eu tic a ls ASBESTOS (?) MINING ISOPROPYL OIL (?) ASBESTOS PROCESSING ASBESTOS WEAVING TAR FUM ES PRODUCTION MANUFACTURING COKE OVEN SERVICING ASPHALT DUST RADIOACTIVE DUS1 PITCH, TAR HEATING ; SOOT; PITCH ,TA R, ASPHALT OUST MINING' . NASAL SINUSES LARYNX LUNG'i m m & kL tv-four luii"; cancer cases were found among VM duck workers at Mull, Kurland, of whom yOOwere exposed to grain dust. There were boiler scalers with lung cancer. Willi the option of I boiler sealer, none had any :ttdiological evidence of pneumoconiosis and IH' 5 had a slight degree of pneumoconiosis Jpnn histological examination. Xo lung canw* were observed among dockers who were W exposed to grain dust. It may he possible 4*1 boiler sealers sustain a carcinogenie expo| Wv io chromate-containing scale, if chromates {.'mused as autirusting agents, or that these | wkers sustain a pulmonary deposition of k*i oxide. Whether specific vegetable matter *fsome rareinogenic contaminant of the grain, ; as residues of chemical fungicides or other , frcerssing or preserving agents, account for the abnormally high ficquencv of lung cancer among grain dockers is at present a m atter for speculation. Mention also may he made of the recent observation of Fatilds on the excessive fre quency of pulmonary cancer among English iron ore workers employed in mining activities at two different locations. Xecropsics performed on these miners during 1932-53 showed a lung cancer incidence of 9 percent (192 necropsies with 17 lung cancers), while post-mortem ex aminations done on 2,378 males of comparable age who were not employed in these mines revealed that only 44, or 1.85 percent, had primary lung cancers. It is remarkable that there did not, exist any parallelism between the degree of pulmonary fibrosis observed in the iron miners and their liability to lung cancer , Hrahh Monograph No. 36, 1955 17 m tuberculous lungs, 2 plus; ill librolic, lungs willioul cancer and/or tuberculosis. 2 plus). The absence of a positive correlation between pulmonary fibrosis and lung raneer w iis noted wbi'ii tin' t'vidi'iiri' on lung riin riT among tin* rndioartivi' on* niini'rs of .loaeliimst bid nnil Solmi'i'liiTg was analyzed (I l neper). Although tin* actual causal factor responsible for the lung cancer among iron ore miners remains (o lie determined, if may be mentioned (lull Levin and his co-worker's recently recorded a positive statistical correlation between an occupational exposure to iron oxide and beat, and cancer of the. lung. The studies of Breslow, lloaglin, Rasmussen, and Abramson ;>1S histologically proved eases of lung cancer in California suggested (he existence of an increased liability to lung cancer for members of the following occupational groups: welders, sheet metal workers, steam fit fees, boilermakers, crime operators, and nonferrous metal smelter workers, that is, individuals who are exposed to metal dusts and fumes; oilers, oil held workers, wipers, and marine engineers, who have contact with oil fumes, mists, and sprays; asbestos workers; construction and maintenance, painters, who inhale vapors or various organic solvents, resins, lacquers, plastics, and rubber, as well as finely dispersed inorganic and organic pigments (chromium, nickel, copper and arsenic compounds, carbon black, aniline dyes); and commercial cooks exposed to fumes and mists of overheated vegetable and animal fats and mineral pan greases. A recent study of the causes of death of the members of the international Pholoengravers Union raised the suspicion of an excessive lung cancer liability for member's of (his occupational group. From the different lung cancer death rates listed for the carious occupational groups, it is obvious that the total number of workers possibly exposed to occupational carcinogens of known or still unknown nature is evidently very large and comprises workers cm cloyed in basic and processing industries, construction, trans portation, services, tr ades, laboratories, and pro fessions (fig. 8). It is, on the other hand, equally clear that the quantity and quality of iin u m ia i.io n available oil the occupy' Ispira tory aspects of lung cancer causation are depl0 E t * i gcnei defective because of an absence of extoii<:|v prolonged analyses of lung cancer deaths various industrial groups for specific E l y 1,c m | r j he cau l p ' ainoi factors. The evidence on hand neverthe), f e . >-l,ecin adequate for demonstrating that the wide v * (ions in lung cancer frequency appIln!^ existing between different industrial popnja, ' Oc. groups are attributable to differences in 1110^ less well-definable occupational exposures * not to differences in cigarette smoking habit * O ccupational Respiratory Cancers and Carcinogens Conclusive evidence of the existeiic. ,/ exogenous carcinogens and environmental r* spirntory cancer hazards is provided by ^ epidemiological, medical, and experimentaliln* concerning occupational respiratory enm*^ A general view of the occupational respirm,*, cancer panorama., including causal agents, vu organs affected is presented in table 10, Scope of luiriroinneiital, L uixj Cancer Ila An indiscriminate acceptance of tlu- f,.^.^ given in table 20 as reflecting the actual scope these identified and recognized respirai.* cancer hazards, however, would be seriouh misleading, despite views expressed by sew* protagonists of the cigarette theory (Hingcrir Wyndor and (indium; Levin; and other Although a definite demonstration of sp-m, occupational lung cancer hazards has so Ut been made for only relatively restricted work* groups, tin1 evidence on hand is not only 13. cquivoeal but also indicates that other work* groups exposed to the same causal agents if subjected to identical or similar working cornialions are subject to the same hazards, h contrast to the apparently low carcinogen*, potency of the suspected, but unidentitiei agent presumably contained hi tobacco smith the occupational respiratory carcinogens vt evidently highly potent, as shown by their mi respiratory cancer attack rates (table 21). Since environmental carcinogens have bn* shown to produce cancers w'herever they opr* in adequate intensity and duration, and e*sidering the fact that many of the occupation* ..man's- - ..I ...Iriim oils ..,,nvl oil- - ilive di' fui al - ('arci t-ui:tIi<* hydro I ..al tar fumi I', Irull imi oii 1 mid sili !-..|irn|iyl oil \.!.<~tos . . . M-I.a! V' - <' r-uuatrs.- N:. k. t Lumini radiati Radioactive 1 E n v iro n m en ta l Causes o f Cancer o f the l " Health ;.u; - :V y < lirfttot'V TOivinogens -cur us imitisi ryiJ ted gttIlcl'!l^ utmiisphoi'ic pollutants, il. may be assumed timi, these pollutants repre- TM the cause of a significant, pori ion of lung i'ijcers among members of the general popula.^ especially those who live and work in j^tJy industrialized areas. The approximate scope of occupational ex posures (o (he various respiratory carcinogens may he estimated from data supplied hy Bloomlieltl and his co-workers. From a survey of l,o0.'i,2()4 workers employed in all industries of 10 Stales, it was found that 7,970 were exposed to fumes and dusts of chromium compounds and *14 20. O c c u p a t i o n a l r e s p i r a t o r y c a r c i n o g e n s un ti c a n c e r s r e c o r d e d lu rin g p a s t 75 y e a r s , t l i e i r c a u s e s , s i t e s , **** and numbers Agent Site of cancer Numlx' r of n*ronk'd vUSO.S Year dis- eovered I 'n i h 'd Stil t<*s Other eoiiiilrle.s 'Total ---- testos....... (Iroiiiates-- Sittel--------- faltar--- - - frfiulctiia oils, propyl o il .. ...Ktdioaclive chemicals. Total---- ----- b u n g ------ ___ d o __ . . . ___ d o .......... . . . d o . _____ . Nares and nasal sinus . Tung---- ----- ----- bung and lanivx. . b u n g . . ___ _ . b a r v n x .............................. Nasal sinus. _ . b u n g ------ . . . . . Nasal s i n u s . . ......... .. 1930 1934 1932 1932 1930 1930 1940 1S79 1931 7 ! 22 i 75 : 0 ! 0 0 1 7 i i 4 l i 0 , 3 I 125 i 1 o 10 i 74 ! 05 . s4 : 51 53 33 0 0 ' 0 025 0 ; 23 90 140 S4 51 53 40 1 4 r, 025 3 1, 120 Table 21. Hcspirulory cancer attack rales, by environ m en tal carcin ogen s Carcinogen .Sites of cancers Incidenee in population at risk Attack rail's Percent of all cancer dentils Itatc per 100.000 _____________________________ Morbidity Mortality ' Aromatic hydrocarbons: Coal tar fumes__________ l a m g ____ : Petroleum oils___________ b illig ------ Carbon and silicon polymers: : -, , .. i'P aranasal sinuses, -V Iwpropvl oil-------------------- j inrllyx. Anbestos______________ In n ig . 500:100. 000 `.>.000:100. 000 1 / 10:100 45 154.5 ( nor mal 0.5). Urtnks: Arsenic. : eliminates. fcamg radiation: 2 ; Radioactive ores _ bung. Lung. .sinuses. L umm: ----------- - - ; __ . 1 . ! (42 X nor! map j 574:100,000 _______ ! i j 1 (20 X nor mal). (13.2-20 percent asbestosis autopsied (O.S-2.4 percent normal)). 145.7 males (10.9 normat.) 140-33S (50-,SO percent of all deaths). 2 * Wir Health M onograph No. 3 6 , 1955 19 Tllofi, lo fumes mid dusts of arsonicals. For industrial workers of all -18 Stairs, respiratory health hazards existed from (li<* inhalation of dust, fumes, mists, and vapors for 45,000 indi viduals employed in asbestos operations, in 'Hi,000 having contact. with arsenicals, in 240,000 inhaling various types of metal dust,, and in '2.500.000 linvm' eut-iineous, respiratory, <1-11(1 digestive exposures to various combustion and distillation products of coal far, pitch, creosote oil, soot, and to petroleum fuel oils and lubricat ing oils, greases, and cooling oils, to name a few. The highly defective state of knowledge con cerning the actual number of occupational respir atory cancers is, moreover, demonstrated by the fact (hat information on the existence and number of such cancers in specific, industrial operations with recognized respiratory cancer hazards is distinctly spotty, not only as to data available, from different countries but, also concerning (hose on hand from identical opera tions of the same country. The following ob servations may illustrate this point. The existence of an excessive liability to can cer of the lung from an inhalation of coal tar fumes by retort attendants of gas and coke oven plants has been established by a few re ports from Japan, Canada, and England. Apart from these isolated data, no others are available for similar operations from these or any other highly industrialized countries (Ger many, United States, France, Italy, Poland, Kussia). Likewise, there is no official record available concerning tin* occurrence of respir atory cancers among carbon electrode makers and attendants in aluminum manufacturing plants, where workers become exposed to dust and fumes from the pitch and petroleum asphalt in the electrodes, and where, according to in formation available from four different countries, tar and asphalt cancers of the skin have been observed as the result of such contacts. It is, moreover, surprising that data on the occurrence of lung cancers among producers and users of arsenical insecticides have been re ported almost exclusively from Europe, al though the United States has beam for many years the main producin' and consumer of these products. Similarly, reports as to the existence of respiratory cancer hazards from an occupa tional inhalation of mists and fogs of lubricating and cooling oils have so far totally origir from Europe, despite the fact that Ameril industries offer ample opportunities for ident exposures, that an excessive liability to cancer has been noted for paraffin pressers i ployed in oil refineries, and that the survey one oil company has shown that there wa marked predominance of operating refin| workers among the lung cancer victims of particular organization. Finally, attention may be called to the that the entire evidence as to the existence! lung cancer hazards for radioactive-ore has come from the observations made inSch berg and Joaehimsthal. However, mining^ uranium ores has been carried on for 10 tof years in the Congo, Canada, and the Unil States and extensive milling operations of African ores have been conducted in for many years without any official recordl similar respiratory complications among workers employed. Additional incompleteness of the existing! orils on occupational respiratory cancers be related to the possibility that pulmon cancers may have their causation from ages entering the body by an oxtrarespiratory rouj While, all known respiratory carcinogens area environmental origin and are inhaled as .1 pollutants, there exists some suggestive occuj tional, medicinal, and experimental evide indicating that agents introduced by oti routes may be effective in eliciting lung cano Several eases of lung cancer are on record whij developed after an oral administration ofsonieals and which appeared in individuals' arsenical dermatoses and skin cancers (Nd bauer). Lung cancers also have been obser in some aniline dye workers suffering fn primary occupational bladder cancer (Mulla following prolonged cutaneous, digestive, respiratory exposure to dusts and vapors certain carcinogenic aromatic amines, possible scientific and practical significance;! these findings is suggested by the experiment observation of lung cancers in 10 percent rats given the potent carcinogen, 2-acetylan fluorene by an oxtrarespiratory route schowsky). A cutaneous as well as parent introduction of coal tar and several polycyc hydrocarbons as well as of urethane resulted j 20 E nvironm ental Causes o f Cancer o f the . 'i d , , -v 'riK>nai^ Amori,-,IfJ , precocious a p p o im m o o mid mi inoroiisod iiuni- jx^rof pulmonnry Illin o is in mioo. jr-Hj ' ,0 h,,,.. '*sers survey ,,| ,pp ;s t'eiill(.p.. s of h,:. Pattern and Type* of lit xpiratnry Cancer I a zanlx If a map of Iho distribution mid relative eon.itiration of Ilie different carcinogenic air pol lutants wore prepared for a riven area, it would vliibit a sort of crazy quilt pattern to which ,l,t. -eiieral atmospheric pollutants would fur- > lie il,,, lene,. r0 lilil,.r, USein,, ,. uhh the overall background color, varying in jqitii between darker urban areas and lighter -iial districts. Other types of carcinogenic ,[i]iosphcric pollutants having a more circum- liiiiin^ ,,ribed field of distribution would appear ns 10 in i m'ularly arranged and variously sized and ' I'llil,,; ns of i|,, Bi'ljrinii, record ,,f long i!.. -hiiped spots and islands of different, colors upi'ninposed upon the general background. 1; lands to reason that such locally differing .\|Kisure patterns arc bound to exert an imvrtiuit influence upon the epidemiological cliar,,n'r and incidence rates of pulmonary cancers iSI.iIijr ,f various ngions, \ one of the various CITS II,,,'. ulinoimr, '111 HgCI>. ii'y roui, ns HIV d IIS :,.r 0 OCCIIp:,. rarriliogens would produce its own epidemi.'liigiral scatter pattern showing a diminishing qirrud of cancers from multiple carcinogenic X'lduction foci. The following three main types of exposure ,,environmental atmospheric carcinogens may v distinguished: eviden, > I. General environmental atmospheric ex- by mil,.* S' caiuvrord win.i, M'lires to certain aliphatic and polycyclic hydrocarbons released into the atmosphere as nannpletc combustion products of domestic on of nr- i aid industrial and ship finds, as parts of the limls will I -\limist fumes of gasoline and diesel engines, as rs ( \, U- ( dinision products of rubber tires, and ns dust obscrvr.i ! 'i'llil asphalted and oiled roads; exposure to ini' froi.i ! irsciiicnls contained in the mineral ash and soot (Miilbr ! d burned coal and in the (diluents of certain five, no.! I aidul smelters, and related to the large-scale vapors I of arsenical pesticides; and exposure to es. Tli- I radioactive material either naturally released licance >! I fromthe soil and from bodies of water or pollut- crimen nd I 1 the atmosphere as (he result of nuclear orront > wplnsions. (yjilinin* I 'special and locally restricted atmospheric 1to flh> i" quislin' to carcinogenic, pollutants of the air mroiU'i-" polyoyt i> esilltcd - exists in the vicinity of nonferrous metal smelt ers releasing in their diluents and from their slag heaps fumes and dust containing nickel, ursenicals. chromium compounds, and berylli um. Similar exposure exists in the vicinity* of carbon black plants, oil refineries, tar distilleries, gas plants, and similar industrial establish ments producing large amounts of soot or other polycyclic hydrocarbon containing effluents, and in thi' vicinity of radioactive ore mills and atomic energy* plants. The individualized type of air pollution con nected with tin' smoking of tobacco, with its suspected carcinogenic hazard to the lung in the special form of cigarette smoking, may be included in this typo of exposure to atmospheric carcinogens. !1. During the last 75 years, an increasing number of specific chemical and physical agents have either definitely been recognized or are strongly suspected of being responsible for the appearance of cancers of the mires, paranasal sinu.jcs, larynx, and lung among members of certain occupational groups. These specific occupational exposures are associated with the inhalation of coal tar and pitch fumes and dusts, mists and fogs of petroleum derivatives, soot, vapors of isopropyl oil. that is. the crude, liquor from which isopropyl alcohol is distilled; arsenic, nickel, chromium compounds, asbestos, and ionizing radiation. Since the available evidence establishes such carcinogenic connections with only some, but not with all, inhalants, such as silica or coal dust, it is apparent that carci nogenic activities are not associated with all atmospheric pollutants. Occupational {expiratory Cancerx The respiratory cancers of recognized or strongly* suspected occupational origin arc im portant. not only as industrial disease manifes tations but also as prototypes of otiologieally and topographically identical cancers affecting workers in other, similarly hazardous occupa tions as well us of those cancers involving an indefinite portion of the general population sus taining for environmental reasons contacts with the same industry-related carcinogens. til* I .uni f"Wic Health Monograph >o. 36, 1955 21 : i a i < i s _ 5------ 4  'h y s lc n r h / m i cal S la lc o f A l m o s j i l n ric ( 'a r c in o <l<-ns a m i T a ju u ji'a fth irnl D ix lr ib i il io n o f ('o n c e rs in /In' H c s p ir o to r y Traci I'u agreement with observations made as lo reasons for die topographical <lisi-nl>u(i<>u id' environmental eaneers in oilier duet, systems (erogenous and alimentary canal), respiratory cancers of environmental origin arc preferably occupying sites wlicrc (a) the How of the inhaled polluted air is interfered with, that is, in the normal narrows of the respiratory tract, stieli as the region of the nasal turbinates and the larynx or its bronchial bifurcations, or (b) where the respiratory tract forms dead end saceulations, such as the paranasal sinuses and the peripheral bronehiolnr regions of the lung, in which inhaled carcinogenic matter may accu mulate, condense, and precipitate. The trallic pattern of air pollutants in the respiratory tract thus corresponds to the distribution pattern of respiratory cancers elicited by atmospheric carcinogens. The second principal factor which determines the localization of an environmental cancer within the different sections of the respiratory tract is represented by the physicochemical status of a particular carcinogen, since this con dition largely influences the site or sites of chief exposure to an atmospheric carcinogen. Car cinogenic dusts consisting mainly of coarse particles are mainly arrested in the nnres, where they cause cancers of the turbinates. The nasal cancers observed among copper-nickel matte refinery workers inhaling the coarse dust of the roasters illustrate Ibis interrelation. 'flic excessive incidence of larynx cancer among mule spinners inhaling carcinogenic shale oil sprayed from the revolving spindles likewise provides another example of this mech anism because it is likely that the relatively large droplets of this oil are arrested in the upper portions of the respiratory tract, making the narrows of the larynx the part of main exposure. Dusts or mists composed of particles having a diameter below 4 microns, on the other hand, penetrate into the deeper parts of the respira tory system and therefore are mainly responsible for the cancers of the bronchi. The bronc genic cancers found among chromate manuf furors, asbestos workers, and coke oven and i retort workers are representative of this type exposure. Atmospheric, pollutants of gaseo* and vapor types not only penetrate into lungs but also into the nasal sinuses, where may be deposited by degradation into soli fradioactive gases), by decomposition into soli" (nickel carbonyl), or by condensation and memo lion into liquids or solids (aliphatic epoj ides contained in crude isopropanol liquor). In assessing the relationship between physicochemical status of atmospheric earcingenie. pollutants and the localization of cance within (he various parts of the respiratory tract, consideration also must he given to the fact th gaseous and liquid carcinogens may become ad sorbed to the surface of earcinogenicaUy inert solid dust particles and behave under such con-' ditions more like solid particles. Such com, binations, for instance, occur in relation to exposure to radioactive gases adsorbed to ro dust in uranium mines as well as concerning thd inhalation of liquid or solid aliphatic and poly, cyclic carcinogenic hydrocarbons adsorbed the surface of mineral road and industrial dust' or of carbon constituting the bulk of soot. The first evidence indicating the existence < causal relations between environmental factor1 and the development of cancers of the lung watrecorded in 1879, when Ilarting and Hesse established the cancerous nature of the lung diseases prevalent among the radioactive-orr miners in Schnccbcrg, Saxony. This discovciy,' of historical importance and great present sig nificance, attracted little attention at the because radioactivity was still an unknown fact and cancers of the lung were comparatively t before the turn of the century and therefore ( little medical interest. It was not until the third and fourth decade* of this century that additional, well-defined occupational activities and environmental agents were, again related to the causation of cancer of the lung and other parts of the respira-* tory tract, that is, the nasal cavity, paranasal' 22 Environmental Causes of Cancer of the Lutili '"(jiuses, :ini larynx. Aimmj; these additions to 5 list of environmental respiratory ennrers i1tre the lung cancers among chromate manujicturcrs (1935). of asbestos workers (1935), of ^senic workers (MWO), and of coke oven opera^rs (1936), the cancel's of the nasal cavity, pnra1b*s81 sinuses, and lung among copper-nickel ifjoelter workers (1932). the carcinomas of the ijsal sinuses among luminous-dial painters (1931), the cancers of the nasal sinuses, larynx, Sgnd lung among isopropanol manufacturers y^l946), and cancel's of the larynx and lung imong workers exposed to lubricating oil k:*vsor mists (193(1. 11)40). &^Specific Carcinogens In organ Ic Chrmteals kv Nickel, one of the most industrially important, petals and principally mined in the. .Sudbury net of Ontario, Canada, has many uses: Iflloys (iron, copper, chromium, aluminum, molybdenum (employed in the inanu^litlure of stainless steel, heat resisting steels, ftrgings, casts, wires, sheets, structural shapes, ' -labing, rods, bars, strips, and so on); electroIj^iting; catalysts; ceramic enamels and colors; Dements in paints and inks; storage batteries, so on. j^Eiposure to nickel fumes and nickel dust of "iic nickel and its compounds or to nickel nyl vapors is, therefore, frequent for indusj|pll workers of many types and in many operu- While skin contact to nickel and nickel IHpUnot infrequently results in the development | 'iUi apparently allergic type of dermatitis, iation of the volatile nickel carbonyl has responsible for an appreciable number of frtrte and often fatal poisonings. The puly manifestations (congestion, desquama- ||W. of alveolar epithelium, fibrinous acellular i**hon into alveolar spaces, bronchial muhemorrhages) are apparently attributable toxic action of finely dispersed nickel from the disintegration of nickel carpiyl ii|H)n tli(>pulmonary struetures. Krall't suggested that these reactions are flic result of a nickel allergy having the lung as its shock organ. The first report concerning tins occurrence of an excessive number ol cancels of the nasal passages (nasal cavity and paranasal sinuses) and of the lungs among workers of the Clydach plant of the International Nickel Company, located at South Wales, England, was made by Grenfell in 1932, all bough the. first appear ance of these neoplasms among the nickel refinery workers was noticed in 1924 (Biuider). Subsequent reports dealing with these cancers were made, by Stephens; Amor; Cooper (E. II.); C'arozzi; Bridge; and Merewethcr. From 1923 to 1948 inclusive, there were reported to the Chief Inspector of Factories a total of 47 cases of cancer of the nose and 82 eases of cancer of the lung from the nickel works. By the end of 1948, 4(1 of the workers with nasal cancer and 72 of those with lung cancer had died. None of the patients with nasal cancer and only 2 of the patients with lung cancer had commenced work in the nickel refinery after 1924, when a recon struction of the plant had been carried out. The average exposure period for the nasal can cer patients was 23 years (range, 3-20 years), and for the lung cancer patients, 25 years (range, 1-33 years). No eases of cancer of the larynx have occurred, and only 1 cancer of the naso pharynx was observed at Clydach. The nasal cancers involved the turbinates, nasal septum, and paranasal sinuses (clhmoids). Of these, the majority were of the undifferentiated cell type (0), some showed a squamous cell character (3), while columnar cell carcinomas were uncommon (1). Of the lung cancers, of which histological studies were available in only 4 cases, 3 were of the small cell, pleomorphic type, while 1 was a squamous cell carcinoma. Similar observations were recently recorded from a Norwegian nickel refinery, where 3 cases of lung cancer were seen (Lpken). In one of these, cases a squamous cell carcinoma was associated with sarcoid lesions, Goldblatt and WagstafF mentioned that so far cancers of the respiratory tract have not been noted among the workers employed at the German nickel refinery at Ludwigshafcn, Health Monograph No. 36, 1955 23 nor lias then' lirn roporloil an iinusinil fre quency of respiratory cancers among Ilie workors of i ho Sudbury nickel oro minos ami smellers in Cumula, although several eases of nasal sinus cancers were, recently soon in one ('anadian nickel plant. Amor pointed out that the majority of indi viduals employed at Clydach who developed respiratory cancers were not exposed to the inhalation of nickel carbonyl hut to that of nickel matte dust or dust from the nickel matte roaster (Lpken). More recent data communi cated by Morgan confirmed this observation, although exposure, to nickel carbonyl vapors had occurred more frequently among the af fected workers than was apparent from the data previously given by Amor. The rela tively high incidence of cancer of the nasal cavity indeed suggests that, a rather coarse par ticulate dust readily arrested at the region of the turbinates may have been active in the production of cancers at this particular site, while nickel-containing vapors or a very small particulate dust most likely account for the cancers of the lung and nasal sinuses. As to the causative agent, various theories have been advanced. Amor favored the con cept that the inhalation from arsenic-containing sulfuric acid used in the refining process was the active carcinogenic agent. I t is most unlikely that this is correct because the nickel refinery workers do not suifer from perforated nasal septa and display no evidence of chronic arsenicism such as dermatosis and cutaneous cancers, which almost always have accompanied the occurrence of lung cancer among workers exposed to arsenical dusts or fumes (irueper). Amor staled that the refined nickel-copper ores are free from radioactive matter. The res piratory cancers observed among nickel refinery workers thus arc not identical in etiology with those seen in miners employed in the radioactive mines of Sehneoberg and Joachimsthal. Workers employed at the roasters, in the nickel carbonyl operation, and in other parts of the plant, on the other hand, become exposed to the inhalation of dust, fumes, or vapors con taining nickel. Nickel is the common denomi nator for all of them. Il thus is most probable that the respiratory carcinomas observed among nickel refinery workers are reaction products more or less finely dispersed nickel particles vapors. There is no evidence available, ho ever, which indicates that the inhalation^ nickel in particulate, or vaporized form ls companied by pulmonary changes of a pneu eoniotic nature. The concept of a nickel etiology of respira cancers was tested in animals by Campbell, ` exposed mice to the inhalation of powd nickel matte and observed that these a had a lung tumor incidence significantly ] (ban that of the unexposed control mice, recent experiments of Hueper seem to dem stratc more conclusively the carcinogenic p erties of metallic nickel. When pure me" nickel powder was implanted into the femo and pleural cavities and subcutaneous tissue' 175 rats, cancers developed at the site of inj tion in 50 of them. Whether or not nickel assumes a carcinoge role for cancers of other organs and follow exposures hv other routes is uncertain. It he mentioned, however, that Araki and demonstrated, by spectrographic metlr nickel in human and animal cancers of vari types and sites. The. nickel content ranged I 0.273 mg. per kilogram of fresh tumor tissue 0.2 ing./kg. No assessment of the degree of occupatio nickel cancer hazard can be made from the available since the number of workers at i unknown. Likewise, no definite opinion be expressed as to the possible existence extent of respiratory cancer hazards for pe" having for other reasons contact with fumes and vapors containing nickel or its pounds. CHROMIUM Chromium as a metal, alloy, or compound used for many purposes in industry. It is, Ibis reason that a large number and variety workers have contact with chromium and i inium compounds and th at even restricted \ of tlic general population may possibly come exposed to these agents in the form of d vapor, fumes, mist, liquids, and solids (Bo and Rushin). Workers most likely to be posed to chromium and its compounds acetylene workers, aniline workers, bleac 24 Environmental Causes o f Cancer of the i-oducts to articles 0r how. ahifcion of ,rTM is i pnouino- >spiratorv \v|,o powder,.,] ! an imug ly higher w'e. Tl,,. > deinoonic pro|,. metalln fcniorni tissue <,f of ilijer. inogeni.ollowiiej It imn id Mur" UOtllod* varioii* ted from fissile I pill ion,,! lie (him t risk i* ion mr. ice itiei person* li dusi. Is com* mini i* t is for idy "f d din*group* lv I*if iiu>t ionrii' he C\Is am idler* liliieprilltees, chronic workers, chromium platers, rhroniatc manufacturers, chromite miners, cray on makers, dye workers, eleclrophiters, enamel workers, glass ami poll cry frost ers. glass colori<ri pottery glazers, artificial (lower makers, l^tery makers, linoleum workers, paint, mak ers ink makers, painters, photographic workfri, pliotoengravers, polishers, printers, rubber workers, steel workers, tannery workers, vulfanizere, waterproofers of textiles and paper, ciders, users of cliromalc anti rust agents in : -ailroad engines, automobiles, steam heat in stallations, and bitumen and oil refinery workers. _\n environmental atmospheric eontamina, lion with chromium compounds may result, [,,mi the release of chromium-containing indus trial wastes of chromate, plants and of oil refineries using a ehromiuin-eontiiining silica .-atalyst for the catalytic cracking of oils. An environmental spread of chromates may also [allowthe use of such compounds as antirusting tm'iits in automob" "nd for anticorrosive foaling of airplanes. Since many of the industrially used chromium compounds exert i corrosive action on tissues, skin contact ind'or inhalation of such agents results in the development of chrome ulcers of the. skin and nasal septum which in turn provide, definite proof of an existing health hazard. Oomraouting on the appearance of such manifesta tions among workers in new industries using rtromium compounds, the Chief Inspector of Factories of England and Wales remarked in ; is report of 1944 that " the control of old Lizards in new industries is of interest to others swell as to the student of industrial health, forit would seem that in many eases the hazard a not recognized until damage to tissue has tan done, when old principles have to he i relearnt and adapted to new uses.'' This reflective observation seems to he quite appropriate when contemplating the possible existence of respiratory cancer hazards for individuals employed in the numerous industod operations for which no pertinent pubfhheddata of any kind exist at the present time. The observation of apparently oceupationwnnected cancers of the respiratory organs, specially the lung, lias been limited so far ta two typos of operations, the production of i dimnintes from chromite ore and the manu facture of certain chromium pigments (zinc cliromalc. barium chromate, lead chromate). In these, operations, both water-soluble and insoluble eluoiniiun compounds are inhaled by the, exposed workers. The chemical nature of (ho actual carcinogenic agent which is respon sible for the excessive liability of chromate and chromium color workers to cancer of the lung is st ill controversial. Although all investigators believe that some chromium compound or compounds are causally involved, if has remained uncertain whether the compounds suspected are hexavalent or (rivaleut, water soluble or insoluble, monoehromulos or dirhromates. Water soluble chromium compounds (monochromates, dieliromalcs, and zinc, chromate) are most often incriminated. Manenso and Ilneper recently pointed out that it mav he more likely that carcinogenic effects are elicited by chromium compounds which an* cither not soluble in water or are only slightly so, because such chemicals, when inhaled as dust, would he retained and deposited in the lung and thus exert a prolonged effect upon the pulmonary tissues. Such chromium compounds present in a chromate, plant would he represented by chromite, ore and its early conversion products preceding the formation of monochromales. These little water-soluble trivalent chromium compounds occur in the material present in mixers and roasters and are contained in the slag which usually is stored for future use in tin* yard area of the plants. Supporting this concept as to the chemical nature of the carcinogenic chromium compounds is the fact that, workers as well as animals ex posed to the inhalation of chromite ore dust have not only a high chromium content of the lungs but also an excessive blood chromium level (Manenso and Urone). Recent experi ments on rats which inhaled finely powdered chromite ore dust showed that after 18 months a chromium level of 13.0 and 17.0 gamma, re spectively, in 100 cc. of blood was found in 2 rats studied. This finding, moreover, definitely establishes the fact that a fraction of the chro mium contained in chromite ore is solubilized in the pulmonary tissues and discharged into the blood. . t un* Health Monograph No. 36, 1955 25 ...... .... u p p u n u i a causal rule of triva- lent compounds may he derived from (lie ob servation that 10 of (he 20 chromate workers with lung cancer reported on by Alwens and Jonas in HITS were, not employed within the manufacturing buildings or were repair men or maintenance workers (blacksmith, glazier, driver, welder, or manufacturer of sulfuric and hydrochloric acid, produced in a nearby build ing). While all of them probably had some exposure to chromates, it is likely that their contact with chromite ore dust, or with dust from the slag heaps containing more or less "insoluble" chromium compounds was much more pronounced (Mancuso; Urone and Anders: Bourne and Yce; Bucket! and Harvey). As the result of the retention of "insoluble" chromium compounds in the lung tissues, there develops a blackish spotty pigmentation and a spotty fibrous thickening of the peribronchial and interstitial tissue where the chromium dust particles are deposited. This pneumoneoniotie condition called chromitosis was described by Andrievskaya and Mislavskava in chromite ore miners, and by Lukanin; Lelterer, Xcidhardt, and Ivlett; and Mancuso and Hueper in chro mate manufacturers. It was produced experi mentally in rabbits by Lukanin. Letterer re ported a chrome silicosis in a polisher in an iron foundry who inhaled silica and chromium oxide dust. While the attempts of Gross and Koelsch and of Campbell to produce lung cancer in mice by exposing them to chromate dust wen1 unsuccessful, Schinz and Vollmann, who im planted powdered chromium metal into the femoral cavity of rabbits observed after more than 3 years, 1 animal with cancer of the. lung, and 1 with cancer of tin femur. It is definitely surprising that, an exci liability to lung cancer has been established far only for chromate workers in Gerrni (Pfeil; Alwens and Jonas; Teleky; Caro; Gross and Koelsch; Alwens, Bauke and Jon^l Lehmann; Marlincck; Gross; Koelsch; Alwi and associates; Goldblatf and Wagstaff) ai^ in (lie United States (Machle and Grogoriug. Gregorius; Baeljer; Hueper; Mancuso at llueper; Imprescia; Division of Occupatioi Health, U. S. Public Health Service) and chrome pigment, workers in Germany (Baadi Gross and Koelsch; Letterer, Neidhardt ai Ivlett). Bidstrup found ft single case of 1 cancer upon X-ray examination of the chi of 321 chromate manufacturers employed for more than 10 years in English plants, whilj no data exist on tins point in regard to mate-producing or -consuming plants in countries, such as Switzerland, Italy, and France. Apart from the excessive frequency of cancers among chromate workers which cording to American observations, ranges l.'i to 21 times the normal frequency of lung; cancers among the general male population, occupational origin of these cancers is strong^ suggested by the, shift of the age distribute toward younger age groups. This is particular! striking for the lung cancers present among; German chrome pigment workers, since 50 per cent of the cancers affected individuals befoneA the age of 40 years, when lung cancers of up?| known etiology arc relatively infrequent (laMe'i ' . I The quantitative data on the chromium con*| tent of various organs and blood of persons wit&| chromium lung cancer have been reported bjt several investigators (Alwens and Jonas; Let*) T ab le 22. Age d istr ib u tio n o f e a se s o f c h r o m iu m ca n cers o f th e lu n g , a cco rd in g to type o f worker Type of worker 21-30 Age (years) j ! 31-40 j 41-50 J 51-00 01-70 71-80 Total : American ch ro m a te _____ German c h ro m a te ______ Gorman chrome pigment. S 1 10 ' 19 10 1 3 , 7 14 12 1 5 i 3 1 1 1 26 Environmental Causes of Cancer of the Niedhurdt and Ivlett; Mancuso and ^ cr). Spannngel recently noted a peculiar ehavii' of the chromium conleni of the blood ^ urine ill ehroiUiitc workers before and jil'ler bedevelopmi'Mt of long e,'t.neer. It was found Jt in chromate workers ilie normal urinary jcrctiou of rlirontiuni et'itses with the develop- 0 il of bmg cancer while simultaneously the jjpod chromium level heroines ('levaled. If ^jjgnned, this ohservtition may have distinct importance in causal, inetaholie, and diagnostic epects. With the exception of 2 e a s e s c a n c e r of ,),e nares (Newman) nnd I cancer of the maxillary sinus (Cioldhlatt and WagstaH') -the lUigwas the exclusive site of respiratory cancers ifogerved among chromate workers. The total junibcr of these cancers is at present around (25 cases from all sources. None 1ms hern ,,ported as originalinjr from nasal septum tdrers. Chromium pnetuuoeoniosis thus seems to ^company the development of cancer of the butg in chromate and chrome pigment mamicturers. It is uncertain, however, whether f Ikepneainonocotiiolie process plays an essential 5% modifying role in the specific- eaneerization ?pcwess or whether it is merely a phenomenon ' f coiueidental eoexistenee. AHSKNH' X'Arscnieals represent a hyproduel or waste pew of the smelting of many ores (copper, line, silver, cobalt, antimony, iron, bismuth, ciackcl, tin, and lead). Arscnieals are present iyiathc smelter fumes and slag heaps. They are S:iatensively produced and used, especially dur'y*gpast decades, as insecticides, fungicides, and Vimniciiles (sheep and cattle dip, grasshopper ; kit, rat poison), as well as u herbicide, especialfit for clearing railroad rights-of-way. Arscnieals (applied as sprays to orchards and vineyards . md are dusted from airplanes upon cotton. .. m, soybean, and potato fields. They are em- j4)T(h1 as wood preservatives, in the maniiy liftare of glass, lead-base alloys, dyest nil's. Wonr.ing and paint pigments, and medicinal fy cosmetic preparations (Mote). Arsenic ad its compounds constitute, according to i - "Environment and Health," a health hazard t: fcr 35,251 workers employed in American in iluslnos. i iut> ut'iutm . estimate of tIt* number of exposed workers, considering the long, allbough incomplete, list of diU'erenl occupations entailing contact with arscnieals given by ( 'hamberlain. The est male, moreover, does not include the rather consider able number of persons who are exposed to arscnieals for purely environmental reasons by ingest log ni-Kcnicnls with fondsl tills contami nated with arsenical insectieidc residues, by consuming drinking water polluted with arsenieals leached into drinking water supplies from mine and smelter dumps, or by inhaling arsenieals released inlo llte air from industrial establishments or hv small- or large-scale dust ing operations of arsenical pesticides. From the published evidence, it appears that environmental and nouocctiputioiial contacts with arscnieals have been responsible in recent decades for the majority of cases of chronic arsenieism and cutaneous arsenical cancers (Xoubauer: Hueper: Arguello, Tello, Maeola and Manzano; Butzengeiger; Bander; Xieberle; Hofmann; Broil: Holmquisl: Montgomery and Waismnn; Cannon; Arhelger and Ivremen; Straube; Bohnenkamp; llansor and Simon; (outlet-; and many others). While the eausal role which arsenic plays in the production of cancers of (he skin on the basis of chronic arsenieism of occupational, medicinal, or environmental origin has long since been (irmly established, it is rather recently that exposure to arscnieals has seriously boon considered as a, principal eausal agent- of cancers of the mucous membranes, such as those of the bronchi, stomach, and bladder. Indeed, today there exists as yet only highly suggestive but not conclusive evidence, linking cancer of the lung with an occupational exposure to arsenical dust. However, in almost all cases of lung cancer for which such claims wore made, there existed stigmata of chronic, arsenieism in the form of arsenic dermatosis with or without skin cancers. The inhalation of arsetieial dust and fumes induces rather frequently the develop ment of perforated nasal septa as well as chronic irritative conditions of the bronchi, thereby creating a .symptomatic, canoerigenic pattern similar to that seen in chromate workers. Under such circumstances, the existence of a causal relationship between cancel' of the lung i' Health M onograph No. 3 6 , 1955 27 .`ind chronic arscuicism appears to he a reason able conclusion. Chest, mid X-rav examinations of 40 workers employed in in arsenic smeller revealed a mild degree of pneumoconi osis (Suupe,). Although Saupe himself did not- discover any evidence of lung cancer among the workers studied--even though they often were, alllieled by hyperkeratoses of the skin and pe,rforaled nasal septa--lie cited the autopsy observations previously made by Sellmorl on 2 arsenic smelter workers who died from cancer of the lung (Teleky). Frommel briefly mentioned the occurrence of a cancer of the lung in a taxidermist who used an arsenical powder for dusting the pells of animals. Four additional cases of lung cancer in slice]) dip workers with arsenic, dermatosis noted in one of these, wore reported by Merewether, while Hopkins and Van Studdiford observed in a farmer living near a cotton field sprayed with insecticides, arsenical dermatosis, epitheliomas and cancer of the lung. The occurrence of 5 cases of lung cancer (Merewether; Hopkins and Van Studdi ford) among only 24 individuals suffering from occupational arsenical dermatosis and epitheli omas caused Xeubauer to wonder whether this is mere coincidence, because only 2 eases of lung cancer were observed among 142 cases of medicinal arsenic cancers of the skin (Russell and Klaber), or whether under occupational conditions the irritation of the, respiratory tract by arsenical dust was responsible for the phenomenon. Henry, commenting on the occurrence of skin cancers among sheep dip workers (1910-22), recorded 2 additional cases of lung cancers among 10 such workers who had cutaneous cancers. He mentioned, moreover, the pres ence of cancers of the left foot, abdominal wall, and lung in a furnaceman in a sodium arsenite factory. Analyzing the mortality ex perience of a sheep dip factory, Hill and Fatt ing found that 7, or 21.8 percent, of the 22 cancers causing death among members of this group were located in the respiratory organs, while 2, or 12.0 percent, were situated in the skin. There were during the period 1910-42 a total of 75 deaths from all causes among workers in this factory. The proportional excess of cancer deaths was mainly attributable to an excessive frequency of cancers of lung and skin, which were, confined to worka in the chemical processes and were ab .among members of the general group who woajjjL be unlikely to be exposed to any specific hazarf# Ferry, Howler, Buckcll, Druett, and SeliiH^M concluded from the. clinical evidence obtain^ th at, after many years of exposure to arsenical^ these sheep dip workers may develop a squamo^ cell carcinoma in the bronchus. 'Flic most, recent addition to epidemiologic^' investigations on arsenic cancer was made In Sncgircit' and Lombard in studies of cana* deaths among employees of several metallurgj. cal plants of unidentified type. Of the toui of 109 deaths from all causes recorded durin the last 25 years, 12 were due to cancer of i | sites, and of these, 0 were located in the lung. The investigators concluded from this evident*4 that " there ire indications that biological^ the human race made the adjustment arsenic in the environment and that onlr^ rarely, when associated with other contributing] endogenous factors such as systemic disease,^ or possibly factors such as radiation, it mj I be capable of upsetting the biological equilib-1 rium" ; and further " that the handling of ? arsenic trioxide in the industry studied doe' not produce, a significant change in the canon mortality of the plant employees; hence oth/ factors in addition to arsenic must be con- j sidernl significant in the causal relationship to cancer." In view of the fact that 50 percent of 1 cancer deaths among employees of one plant sue j veyed were caused by cancer of the lung, the observations made in fact strongly suggest eareinogenic action of inhaled arsenic trioxide upon the tissues of the lung of the exposed workers. 'Phis interpretation of the data of SnegirelF and Lombard is supported by the high incidence of lung cancers among tl population of several counties in Montana where copper smelters and mines were operated for many years, creating an occupational and j environmental pollution of the atmosphere and soil with arsenicals. Prolonged inhalation of arsenical dust and fumes appears to produce an increased liability to cancer of the lung (table 22). However, the existence of such connection* 28 T a b l e 2.1. c a n c e r m o r t a l i t y i n s e v e r a l M o n t a n a c o u n t i e s . 1917--Ml ( L u l l a n d W a l l a c h ) 1 County and tota l population 11110 M ajor industry rwf Lodge, 13,027__ __ Copper smelling 3_ aver Bow', 53,20<-------- ; Copper mining 3------------- ^scader 4 M " ........ ........ Copper mining, sm e ltin g 11 Gelatin, 18,209------------- A griculture------------------- Number lung cancers Mule mraelo 21 0 27 2 20 1 a 1 0 , 1Total ; I 21 2!) 25 ; 1 Total i cancer deaths 1 1 98 i 259 : 299 ; 81 Percent lung ! cancer 1 i 1 Mule I re malo ; i i 30. 8 ; 0. 0 ! 22. 0 ' 1. 5 ! 12. 7 : 3. 5 1 3. 0 i . 0 i ' Annual lung I cancer death r a te /100,000 i Male -5 mr aele ! 145. 7 48. (i 41). 3 ! 5. 2 1 i 0. 0 3. 9 12. 3 . 0 i personal communication of unpublished d ata. The estimated crude death rate for lung eanci amont: while mules in the entire Tulle 1 Slates in 1947 was 9 per 100,000 population. ** The workers employed in copper ore mining a (1 smolli nu; inti ule hist 111(1 fuuu s of arse'Ilio VA mtaincri in lite grind released as a byproduct and waste product during the smelt ing process. jboultl be acknowledged only when there firistftl at some lime clinical and, if possible, listolopcal and biochemical evidence of chronic mcnicism. In view of the absence of any mill evidence associated with chronic arseni(n among the nickel refinery workers alfeeted Jr cancers of the nasal cavity, paranasal 'Buses,and lung, and among excessive tobacco : mokers with cancer of the larynx and lung, ''t is most unlikely that exposure to arsenic |#t, fumes, and vapors plays any role in the i production of respiratory cancers in members f these population groups. inox The extensive production anil use of various typesof iron and of diverse iron products offers Inquent opportunities for the inhalation of t'nttl and fumes of iron and its various alloys lad compounds by iron ore miners, arc welders, Lpisdcrs, polishers, silver finishers, and metal natters. t The resulting red or black siderosis caused by |j|dbnonary retention of Fe20 3 or of FcsOTTO. /^ptctively, is considered an inert form of ^tnunoconiosis which does not cause disability jfeiad which it least in part seems to be reversIpi. The deposition of iron oxide particles *S*" not. elicit in the lungs a progressive and IplijHked fibrosing reaction unless the inhaled also contains silica, producing then a P^rosilicosis. -iThc coexistence of siderosis and cancer of 'ias occasionally been observed (Slew- art and Faulds, 1 case; Drey fuss, 3 cases in watchmakers; Vorwald and Karr, 3 cases in hematite miners; Simons, 1 case in a blaster of iron casts). It may be mentioned, moreover, that Kennaway and Kcnnaway reported a 2.25-fold incidence of pulmonary cancer among metal grinders and that Turner and Grace as well as Campbell noted an excessive frequency of lung cancer among metal workers. The most recent contribution to the. problem of siderotic cancer of the lung was furnished by Faulds, who noted Unit among 192 iron ore miners coming to necropsy between 1932 and 1953 there were 17 lung cancers (8.85 percent). Ehrhardt and Glithert, on the other hand, noted that, red siderosis of the lung does not produce a special predisposition to lung cancer. The uncertainly existing in this respect is further illustrated hv statistical data provided by J. W. Brower, Deputy State Registrar, Minnesota Department of Health, on the num ber of deaths from lung cancer among iron ore miners residing in St. Louis and Itasca County (total number of miners, 13,313) against that of residents of Minnesota (population base, 2,982,483). There prevails a consistently higher lung cancer deatli rate for iron ore miners for the 5-year period than that noted for Minne sota residents (table 24). Experimental studies on animals exposed to iron oxide and hematite, respectively, gave con tradictory results as to the production of lung tumors. While Vorwald and Karr, using guinea pigs and rats, failed to obtain lung cancers witn Health M onograph No. 3 6 , 1 9 5 5 29 T ab le 21. D entils lue to e a n e e r o f th e lu n g am oiifi iron ore m iners am i residents of M innesota, (lirow er) 1950-51 V( ar Number of deaths Death r : t p e r 100,000 i | Minnei sota resii deuts j St.. Louis-i Minne I tasca j sota resi County dents miners j St. EouisI tasca County miners 1950. ______j 32S 1951 . 2S9 1952 . . _ . , 329 1953. _____ 3(i7 1954. 315 5 ! 11. 0 4 i 9. 7 12 ; 11. 0 S i 12. 3 (t 11. (I 37. (> 30. 0 90. 1 110. 1 (0. 1 hematite dust, Campbell reported mi increase in the number of lung tumors in mice exposed to iron oxide over that of the control series. When the available evidence is viewed criti cally, it is still uncertain whether an exposure to iron dust conveys an abnormal liability to lung cancer. Although Warren and Drake recently concluded that the development of primary carcinoma of the liver as a sequela of hemochromatosis apparently depended in part on the intracellular deposition of iron, such considerations may not necessarily be applicable to pulmonary siderosis and eaneer. However, thorough and comprehensive epi demiological data on the incidence of lung cancer in workers exposed to iron dust are not available. Hence, a definite conclusion on this problem must be withheld. The availability of conclusive information on this point appears to be urgent, in view of the suggestive evidence recorded bv Faulds and because of the fact that damages have been allowed in the past by court action in at least one case of cancer of the lung, in the production or aggravation of which the inhalation of steel dust was alleged to have played a significant role. BKRYLMUM Beryllium is a metal which has found signifi cant industrial use only since about 1920. It was not until about 1940 that beryllium and its compounds were extensively employed for numerous purposes and products (berylliumcopper, beryllium-aluminum, and berylliumnickel alloys, glass, phosphors in fluorescent lamps and noon tubes, atomic energy proflUrtj] t Aldwte ci'ramics, refractories. X-ray tube 'vin(j D.l own tin vitreous enamel, radio tubes, textile fibers {fftain tb mantles'). It is evidently for this reason il! ! plasma rP untoward ('(feels in persons exposed to the - * bh"'1- ? halation of dusts and fumes of beryllium '{twin bein its various compounds have been recognj^ The me only during the last decade. These manifestI. pounds ol lions were of both acute and chronic nature {*c! that far as the respiratory organs were concern^ non of (acute beryllium pneumonitis, chronic pnPB- juiravono moeoniotic granulomatosis, berylliosis). Sor> investigators used the term "sarcoid" tl ^ scribing the histologically peculiar, pulnioiurr manifestations. I t is remarkable moreor* that chronic, berylliosis has appeared not onlr among exposed workers, but also among HT. mg l,0'v<1' jtum silk quently C ad othc oxide, be introduce' sons living in the neighborhood of fluoresce : rrspirator lamp factories and inhaling their beryllium, Sissons; H containing effluents (Eisenbud, Berghout and Steadman; Eisenbud, Wanta, Dustan, Stead, man, Harris, and Wolf). Urgent, : period for Cointtn Similar observations on occupational herd, ostoogeni' liosis were reported from Germany, I(g)T of herylli England, Russia, and Canada. Not min. noted tin quently, similar granulomatous lesions bar dying ""if been observed in other parts of the body aflw , tide ainoi the usually traumatic introduction of beryllium r following dust, especially of beryllium phosphors from years, CO broken fluorescent tubes. The skin of the turn exp1 fingers and hands was the most frequent, pounds extrapulmonary location of these reaction!.. Uirougho' Beryllium granulomas have also been found in fact that the nose and in the anterior ocular structure. Wen repc It is noteworthy that beryllium apparently : of poorly once inhaled is retained over a long period of "ivontuati time in the human body, since beryllium has umably, been detected in the urine up to 10 years aft would b< cessation of exposure (Klemperer, Martin, and rabbits, Van Riper) and has been demonstrated in the over a p( lungs of rats 1 year after the inhalation of whether beryllium oxide (Dutra, Largent, Choltk. beryiliun Hubbard and Roth) as well as in their bon Barnai (Stokinger, Steadman and Root; Barnes), coma fre where it may replace calcium. The skeleton possibly retains the bulk of tlic beryllium in the body far, only (50--80 percent) if the inhaled aerosols air opment soluble compounds, such as beryllium sulfatt administ and beryllium fluoride; the lungs retain tl* direct int bulk of beryllium if the compounds are in soluble, such as beryllium oxide. Experiment imo the cavity, a 30 E nvironm ental Causes o f Cancer o f the Lw* PMic H i f e 1,. ge, llames, uul Donz, moreover, have that beryllium ions react rapidly with jttain tissue proteins and form complexes with a proteins when introduced into the Rd, These complexes protect the, beryllium being precipitated by phosphate ions. Themetabolic, peculiarities of beryllium eomylpindaobtain special importance in view of the r that Gardner in 1940 reported the proilucnof osteogenic sarcomas in rabbits injected Ravenously with insoluble boryllium-eonlainpowders (beryllium phosphate, zinc, beryljRi silicate). Other investigators sulrseyntlv confirmed these results with the same other beryllium compounds (beryllium IpJe. rcryllium silicate, metallic beryllium) into rabbits by the intravenous or lipiraloiy routes (Sissons; Barnes, Denz and ,|Roqs;Hoagland, Grier and Hood;Nash; Dutra, ijirgent. and Both; Barnes). The preparatory wtA for the sarcomas was 11-24 months. ['Commenting on the successful production of cnic sarcomas in rabbits after inhalation ibtryllium oxide, Dutra, Largent, and Roth the fact also that the bones of persons with berylliosis contained not inconsidcrimounts of beryllium. They came to the ing conclusions: "During the last 20 considerable numbers of persons have exposed to dusts of poorly soluble com- of beryllium in various industries out the United States. Despite, the that cases of cancer of this type have not reported, it is possible that the inhalation iy soluble compounds of beryllium may te in osteogenic sarcoma in man. Prey, the incubation period of such tumors be considerably longer in man than in and observations may be required period of years before it will be known persons who have been exposed to arc prone to have such tumors.'' also suggested that osteogenic sarfrom compounds of beryllium "might ly be another industrial hazard." So i.vrabbits have responded with the develBt of osteogenic sarcomas following the tion of beryllium compounds. The introduction of powdered beryllium metal femoral cavity of rats, into the pleural flhtnd into the paranasal sinuses failed to elicit a single, neoplastic response at the site of injection in any l of the 8f> animals used within an observation period of 2 years (Hucper). When in 1948 11neper proposed that the sarcoid pulmonary manifestations of berylliosis might he followed by outright malignant lesions in the lungs, this suggestion was received with a great, deal of skepticism. The recently reported successful production of bronchogenic carcinomas in the lungs of rats which, over periods of more than 1 year, inhaled dust of soluble and insoluble beryllium compounds (Vorwahl), however, makes the appearance of such delayed malignant sequelae in man a distinct possibility, especially as several cases with coexisting berylliosis and cancer of the lung have recently been observed (Kahlau). In view of the established occupational as well as general environmental occurrence of human berylliosis, it may be pointed out that the dis covery and identification of this pneumoconio sis was definitely facilitated by the distinctive and definitive histological features of the dis ease. If these manifestations should be fol lowed by the development of cancers of the hones and lungs, the establishment of causal relations between a previous exposure to beryl lium and the subsequently appearing cancerous reaction would appear to he rather easy. The studies on the toxicity and carcinogenic ity of beryllium compounds indicate that the toxic and cancerous manifestations are to be considered as responses to the action of beryl lium itself and not as the result of the associated anions of its acidic salts (Slokinger, Sprague, and Hall). In considering possible future car cinomatous developments in persons with pre vious exposure to beryllium, some consideration also may be given to the toxic effect exerted by beryllium on the liver leading to the develop ment of cirrhosis and to an impairment of the metabolic and detoxicating function of this organ (Aldridge, Barnes, and Denz; Hoagland, Grier, and Hood). Organic Chemicals COMBUSTION AND DISTILLATION PRODUCTS OF COAL The apparent innocuousncss of coal and, possibly, graphite dust as respiratory carcin ogens is not shared by the incomplete combus tion, distillation, and hydrogenation products * H*lth Monograph No. 3 6 , 1 9 5 5 31 :: ' ':i r of coal (pitch, lar, sool, creosote oils, anthracene oils, tar oils, and highly viscous oily and tarry fractions obtained by (be direct- hydrogenation of coal employed by (be Bergius process/. The carcinogenic action of these combustion and distillation products of coal on man and experi mental animals has been established beyond any doubt. Although the bulk of the casuistic, and epidemiological human evidence of occupa tional coal tar and pitch cancers has come, from England and Germany, it cannot- justly be assumed that American-made coal tars, tar oils, creosote oils and pitches differ fundamentally in their carcinogenic properties from those manufactured abroad. The exposures sustained by the numerous types of American workers in a great variety of occupations and operations do not seem to differ from those found for their European colleagues, nor arc the carcinogenic effects on the skin of these workers at variance with European observations. However, in addition to skin contact with these products of processed coal, there exists for some groups of workers a considerable exposure to these agents in the form of dust or fumes (tar distilleries, tar paint, shingle, roofing paper, paper conduit, and battery case manufacture, gas works, coke oven operations, road construc tion and repair work, roofing, brickmaking, foundries, furnace attendance, railway engine driving, roundhouse operations, pickling of lumber, chimney sweeping, cork brick manu facture, electrolytic metal production, and so on). Since the high boiling fractions of synthetic oils produced by the direct hydrogenation of coal through the Bergius process have been shown to be highly carcinogenic to the skin and/or subcutaneous tissue of mice and rats, respectively, certain types of workers manu facturing and using such products and inhaling fumes or mists of these carcinogenic petroleum and tar oil substitutes may have a special lung cancer hazard. Manufacturing plants using the Bergius process have been operative for some 20 years in Germany and have recently been constructed by several industrial concerns in the United States. Not only the environmental, but also to a greater degree, (tic occupational inhalation of dust, sool, and fumes produced by the incom plete combustion of coal results in the develop ment of a "soot lung," called bituminosis, 32 which is characterized by the deposition ^ finely dispersed carbon [/articles contaminate with hydrocarbons normally contained in COt| tar in the interstitial lung tissue. Koent genological changes may appear in the ltltl * after many years of exposure to high conc<^ (rations of soot in the air inhaled. While tl* pulmonary deposition of small to moderai, amounts of soot in the lungs, such as is con, monly found in inhabitants of industrialize regions, does not elicit any appreciable fibrou* proliferations, massive storage of soot particle* in the lung tissues may finally be associate with an increase of the interstitial connective tissue and with pseudoglandular formations o( peribronchial alveoli. The human evidence relating exposure t the other (100) hm following jriis stoke crime ope :G: PTM asphalt ' painters, and auto; moreover among er .Vdditit vided by iterator plants ai Canada t Kawnhat coal tar and pitch dust and fumes with *a increased liability to cancer of the lung is ncx extensive and is in part controversial. invest iga cases of workers ' The human evidence relating exposure to rod tar dust and fumes with an increased liabilitr to cancer of the lung is equivocal. Kennav&v and Ivennaway slated that "coal tar in iht atmosphere, whether derived from roads, dome*, t tic chimneys, or any other source, does not cause an exceptionally high incidence of cancer hot tar h lung can employee general i generatoi employe occurred of the lung." A similar statement was made (33 porct by Hugouncnq and by Hustcd and Biiimana J. lung car in regard to the liability to cancer of the lung varied fi for workers employed in the tar industry and being 1C in the construction and maintenance of tarred recently roads. McLaughlin did not find any lung ers. Of cancer among 3,059 foundry workers subjected i workers, to clinical and X-ray examinations, although cancer o there were 3 deaths from lung cancer among etlunoid 04 deaths from all causes. Mcnz recently upper nr reported that of 93 workers in Swiss gas plant* It is li who died during the 1926-46 period, 21, or 22.4 rates mi percent, died from cancer of all sites, thereby Followir confirming previous English experience that 25 skin workers in tar and pitch operations have u> had bet excessive liability to cancer in general. Iso during a lated observations of lung cancer in worker of lung com pan exposed to the inhalation of tar fumes were t cancers made by Koelsch (blacksmith, tar worker). cases of Rodenackcr (briquette factory worker), s From Miillschitzky (tar worker). / the inha In an analysis of lung cancer deaths among of eerta members of different occupational groups forthe i plants,; years 1933-38 Kennaway and Kennaway, on E n v iro n m en ta l C auses o f Cancer o f the t**l | Public I JjOother lifiud. noted llint ;m above-average (100) lung <:<i<('! frequency existed for tlie following occupnlions: gashonse workers. 129; ^ stokers, ->s l ; gas |>io,lu<-<.rs. l>02 : gasworks ganc open) tors. 13S; gasworks superintendents, 136; printers, 119; chimney sweeps. 119; jsphftlt workers. 104; metal polishers, 174; painters, 120: tmoors. 141; street- cleaners, 109; jjjJ automobile drivers, 149. They recorded, poreover, a ninefold inoreiisc of lung cancer among employees of a Canadian pis plant. ^Additional supportin': information was pro- Stiied bv the observations nmde among Japanese ypncrouu' gas oven workers employed in steel implants and among gashonse retort workers in [ Canada ami England (Kawahata; Kuroda and fr&wliata; Cruiekshank; Doll). The Japanese ( prestgators found, within a (i-year period, 21 ftfes of lung eaneer among generator oven fWkcrs who were exposed to the inhalation of Mot tar fumes when stoking coal. An excessive :v(H1g cancer rate was absent among workers gaploycd in other parts of the steel mills. The fjpwal incidence of lung cancer among the, xpnerotor gas workers was 5 per 1,000 workers sanployecl. Seven of these 21 lung cancers incurred in workers agetl 40 years or younger vf{3percent against 18 percent in cryptogenctic ijaag cancers) (Hueper). The exposure time nried from 9 years to 2.4 years, the average 1G.6 years. Similar observations were vJKWitlymade among Canadian gashonse work- in*. Of 14 cases of cancer among retort house Apwkcrs, Gwere due to cancer of the lung, 1 to accr of the larynx, and 1 to cancer of the ^ittmoid sinuses (57 percent were cancers of the kipper and lower respiratory tract). : It is likely that similar lung cancer incidence may exist among American tar workers. 'Fallowing a visit to a tar distillery where some ;,JSikin cancers and more than 80 pitch warts been bserved among the 300 workers ;Mingan 8-year period, there was found 1 case dluiig cancer. Subsequent inquiries made by yJBBjpanv officials brought the number of lung . in this and other tar operations to G '**Wsof cancer of the lung. Irom the evidence available, it appears that . inhalation of tar fumes sustained by workers , tffwtain operations (coke oven, generator gas ,JwHs, gas plants, tar distilleries) seem to have an excessive liability to cancer of the respiratory tract. It is not unlikely that a more thorough and competent, analysis of the death records of other workergroups, which have so far been found to lack such tendencies, might e x te n d th e typos and number of tar and pilch workers having an abnormally high respiratory cancer rate. A recent observation of lung cancer in a worker exposed to heated pitch and asphalt points to another source of occupational pulmonary' tar eaneer of definite practical importance (Patch). 1' KTnOI.KUM, S lIA U i Oil,, AND NATURAL GAS The carcinogenicity of certain high boiling fractions of petroleum and oil slmlc, as well as of the combustion products of some of these petroleum derivatives, such as oil shale and natural gas, have definitely been demonstrated not only on experimental animals but also on workers developing cancers of the skin after prolonged contact with these agents. Known carcinogenic chemicals, moreover, have been isolated from these petroleum derivatives as well as (heir combustion products (Bercnblum and Seiioental; Fischer, Priestley, El>v, Wanless and Kehner; Falk, Steiner, Goldfein, Breslow and Ilvkes; Waller; Kehner; Kotin and as sociates.) In addition to skin contact with carcinogenic petroleum derivatives many' workers are also exposed for occupational reasons to an inhala tion of oil mist or fumes (workers in paraffin pressing operations, certain groups of oil refinery' workers, spinners, inotal lathe workers, foundry' workers, metallurgical workers, printers, and so on). In spite of this established occupational respiratory exposure to petroleum and shale oils, there are on record only' tlirce eases of oil pneumonia among such workers, although such conditions have rather frequently been observed after repeated medicinal instillations of mineral oil containing nasal drops (oil aspiration pneu monitis or paraffinoma of the lung). In fact, two eases of cancer of the lung apparently' developing on the basis of a medicinal mineral oil pneumonia have been described (Wood; Sante). The occupational evidence available or pub lished on this aspect of cancer of the lung is rather scanty and in part controversial. Kcnnaway and Kennaway found a relatively high ^ Hralih M onograph No. 3 6 , 1 9 5 5 33 niti<> of laryngeal but not of pulmomiry cancer in mulespinners, who inhale a misl of the carcinogenic sliala oil lubricating the1 spindles. Southam nolod dial mulespinners occasionally dcvelo]) multi])lc primary cancers involving Ilie sloniach or (he lung in addilion to cancers of the skin. Scott, on the other hand, staled that he had not observed a single case of lung cancer among shale oil workers. Huguenin, Fauvet, and Bourdin, who ana lyzed a series of 112 lung cancers for possible etiological factors, found that IS, or lf> percent, were metallurgical workers exposed to the inhalation of nebulized lubricating and culling oils. S were chauffeurs. 5 were mechanics, and 1 was an engineer. Ilugueuin and his associ ates concluded that, their observations indi cated an excessively high frequency of lung cancer among workers exposed to vaporized or nebulized lubricating oil. While the study of Gafafer and Sit greaves on cancer morbidity and mortality among the male employees of an oil refining company did not reveal any abnormal liability of the members of the occupational group to cancer of the lung, this judgment may have to be revised, at least for certain types of refinery workers, according to more recent and scrutinizing observations. Rsch observed three primary cancers (skin, stomach and lung) in a paraffin worker. Touraine and Bour also attributed the development of pulmonary cancer among certain worker groups to lubri cating oil mists. Such exposure conditions may account also for tin* excessive lung cancer mortality among male metal grinders observed by Turner and Grace. There is, moreover, some evidence available indicating that the inhalation of mists or fogs of certain processed petroleum oil fractions also conveys an increased liability to cancer of the lung. During a recent survey on cancer inci dence among employee's of a large oil refinery, the surprising observations were made that there was not only a highly excessive incidence' of scrotal cancer among employees of the paraf fin pressing department but that ine'idene'e of cancer of the lung was also excessive. Paraffin pressers, who represent about one-tenth of the1 total employee! worker group, furnishe'd 56 percent of the lung cancer observed. Since soot as a waste or comme'rcial product has bi'en found to be carcinogenic and to conti known carcinogenic hydrocarbons, a thoro- and competent survey of occupational groups particularly exposed to the* inhalation of (operating railroad personnel; stokers; carhop black manufacturers; rubber, paint, and makers; painters; soot burners; printers; d engine drivers; carbon electrode manufacturer! and users in aluminum plants; smudge poj operators; phonograph record makers) is urgent necessity. The negative conclusion^ reached by Ingalls as the result of a survey the carbon black industry are based on evideni of dubious merits, because only 79 of the f evaluated workers have been employed for years or more in the industry. Since the major ily of known occupational lung cancers havi an average latent period of over 10 yeartf Ingalls' conclusions are actually based on living and active workers. It stands to reason1 that an analysis of the death records of fortni carbon black workers may have told a different' story, especially if the diagnoses were based autopsy findings. Such investigations woi also add to our knowledge as to the existence* extent, and type of bituminosis which might b* expected to exist in workers inhaling fine! dispersed soot particles. . At the present time, exposure to tar, asphalt, heavy fuel oils, lubricating and cutting oils, soot from domestic furnaces, incineratoi * industrial power plants, oil refineries, plants, metal smelters, carbon black factoric*! oil dumps and smudge pots, as well as exposure, to the diluents of diesel and gasoline cnginci| represents the most widespread occupational; and environmental contact with carcinogenic-1 material. The specific carcinogenic agents eon-; tained in these carbonaceous matters are certain, specific aromatic hydrocarbons, which not in frequently are attached to carbon particles gife ing rise, when inhaled, to bituminosis or authi*| cosis; or they are constituents of oily matUf- whieh, when inhaled and retained in the lung^ cause oil pneumonia or paraffinoma of the lung,- Since pure anthracosis is not causally rela to cancer of the lung, the pneumoconioses coinpanying respiratory carcinogenesis by matic hydrocarbons do not play a primary essential role in this process, although pneumoconioses may lower the intensity 34 E nvironm ental Causes o f Cancer o f the a -s > ; r-,. prolong tlxt' duration o! (In* ollVct. of tin' specific ^rcinogomV chemicals oil (he lung tissues. Since our civilization and economic life lias been.built- around llie production and use of the hisie carbonaceous substances and their deriva tives, it does not seem feasible to attain com plete protection against exposure1 to these carcinogenic chemicals with (In1preventive and propliylaetie engineering and sanitary measures practical and economical at the present time. There is, however, no doubt that a great deal remains to be done in this respect and that we sre still rather far removed from having (be maximal amount of possible reduction in expo sure to the respiratory cancer producing hydroeurlwns contained in the various carbonaceous substances mentioned. Carbon and Silicon Polymers Kerent studies of English investigators (Hen dry, Homer, Rose, and Walpole; Ilendry, Rose, and Walpole; Haddow) have furnished i new and intriguing concept as to possible combinations of carcinogens with tissue proteins through the postulated formation of cross linkages between certain types of carcinogenic chemicals and the macromolocular fibers of chromosomes. This hypothesis was evolved fromevidence obtained in the study of carcino genesis by nitrogen-mustards, diepoxides, polvctliyleiieimines, and related compounds. In viewof the fact that one of the various menus by which these substances may exert their specific action in tin* cells is through polymeri zation, it is assumed that polymerized epoxide chains might interreact with proteins or mueoproteins of chromosomal origin, by cross linkage with multipoint attachment, and there by cause mitotic aberrations. The initial re action of one of the epoxide groups of mono meric molecules with the cell component also may start a process of polymerization by being followed by a self-condensation of the free epoxide groups into a polvethencoxy-structure. These concepts are important in connection ill respiratory carcinogenesis for several reasons. Since Oppenheimer and associates; bruekrey and associates; and Zollinger have 'iiowu hat a parenteral implantation of 'arums polymerized plastics (cellophane, polyethylene, polyvinyl chloride, polymethyl methacrylate, polyamide. Teflon, and others; into rats and mice are followed by the develop ment of sarcomas at the site of ((('position, there, exists the possibility that the inhalation of vapors, mists, and dusts of the monomers and polymers of these and related chemicals for occupational reasons may create a respiratory cancer hazard to man. The more immediate importance of these concepts, however, lies in their application to the production of occupational respiratory can cers by a silicon polymer, asbestos, possibly also by a carbon polymer contained in isopropyl oil (polypropylene or propyl epoxide). The probability of such an action mechanism, more over, is supported by observations of lung cancers among .Japanese mustard gas manu facturers. ASBESTOS Asbestos (Hirers from the ordinary giant molecular crystalline silicates not only in its chemical and physical properties, but also in the anatomical aspects of the pneumoconiosis produced by it. In contrast to the tridimen sional polymerized silica crystals in which no oxygen atoms are left carrying charges to attract positive ions, asbestos consists of giant fibrous molecules composed of polymerized silico-oxygon (efra hydra which arc arranged in chains or bands (1'arkes). Depending on the origin of asbestos, the fibrils may be short or long. Italian, South African, and Australian asbestos (amphibils) consists of fibrillar or ra diating crystals of calcium-magnesium silicate or sodium iron silicate (40 percent iron oxide). Canadian, Russian, German, and French as bestos is hydrated magnesium silicate, which contains small amounts of iron oxide (5.75 per cent). Canada furnishes about 75 percent of the world production of asbestos. Canadian asbestos, because of its long fibers, is especially suitable for textiles. Depending on its physical characteristics, asbestos finds numerous uses (textiles, filter material, building material, gaskets, insulating material, adsorbants, and so on). Some 35,000 workers in the United States are exposed to asbestos dust. It is asserted that inhaled asbestos dust pro- Public Health Monograph No. 36, 1955 35 duee- :i-4>e-l i >-i~ mils ll l l i r i t; 11;1 11Ii lib er- :11V ">iS111111111 \ Innu I n l i e :11>~t11<i nl lihruus - I n i e l m v . 11 ir d u - l I- '.-ml In lie m r r l ( W v r i s ; \ him ;i 1I. I)urk:m. :llnl IVat I U S in r r the l.l ILl'cr lllll'ils ill'i' !l1'1`e--I-d in ill.- bi-.Mi.-liioli-r* '( i;ir<111<t i. 111' granulomatous react ions inriii Ix'i'iI>!<>m-Iii<i|:tr llbroiis enli's with yianl cells and asbestos Imilics. These have ;i lilil'ill.'ir cure .-uni ,-ui iron staining |ii'<iiciiiic nr <-<>li<>i<hi I silicic ,-iciil sliciiili. Wlicilicr iiic iron in die si ic:t 11is originates (mm die asbestos libers nr is ilcrivcil from blood nr lissiic cicmcnis is still cniii mvcrsial. Tlicsc two observat inns de serve s|ieeial meniinn liecanse nf die a|i|)areiil dependence nf cancerous el inHires in die lungs of asliesios workers upon (lie presence of asliesInsis and in view of die possibility dial die proteins nl die limy dssue may specifically interreact willi free groups of die lilameiila.ry asliesios mnleeilles (Druekrey and assoeiatesi. I lie coexistence nl asbeslosis willi ealieer of die lung was lirsi reported by Lynch and Smith in I'.KCi (I easel. They later recorded 4 addi tional eases (Lynch and Smith: Lyiieln. Simi lar observations have subsequently been re corded from this country (Stoll, Lass, and Anyrist. I ease: Holleb and Angrisi, eases: and llomburyer. 4 easesi; from Canada (Deslneitles. Kossean. (ilroii.v, ami Sirois, 2 eases: ('artier. 4 eases: Rousseau. I ease); from E.ngland (Ciloyne. 17 cases: Ifarrison. d eases; Merewether, dl eases; Curelou, 1 ease; Owen. 1 easel, and from dermany (Nordmann. 2 east's; Lin/,bach and \\ edler. 1 ease; Horning, 1 ease: \\ el/., 2 eases; Hobme. I ease: noineniei, 2 eases; and Rainier. I ease). Tims, there is at present a total of SO eases of asbeslosis cancer of the limy on record. To this number must perhaps be added the S eases of cancer of the lung complicated by asbeslosis which Ivcnnaway and Ivennaway discovered in an analysis of the death certificates of males registered between 1021 and I'.ldS. Eleven additional eases of asbeslosis cancer of the. limy in workers in two Enylish plants were recently reported by IDoli. who fidt from his statistical analysis that there exists a definite eaitsal rela tion between these two conditions (table 2d). Merewelher noted that the mean aye of males with asbeslosis cancer of the limy was do.2 years (ranyc 22-72) and that Iheir mean expo- - iiiv time w;i> 2D. 1 years tranye ii 40). while t mean aye of female eases was 44.(i years (ran 42 71 i ami their mean exposure lime was < years (ranycO.d -IN). However, in iiimiv cag ihere elapsed a lony exposure-free interval ran iny from several months to 2(1 years before t| limy cancer became manifest (Wedler; W y e rs The aye distribution of asbeslosis cancer, the limy was; I :tl M.V-1 I i;> i .V> -it I Cant cIannne*9 ] } .................... I Tut Ml Since limy cancer of unknow n etiology occur rather fre(|iiently liefore the aye of 40 and sine 20 percent of the asbeslosis cancers appear before i he aye of 44. it seems that there existsi moderate shift toward younger aye groups lot cancers associated with asbeslosis of the lun| The exposure time for asbeslosis lung cancer, excluding the series of Merewelher. was: * Fjp o tn rt lime (years) Clanntfi canut i - : t ____ ________ _____________ ______ _ ______________ t-m ........................... ............. ............ ........ I 1-20 .. . . . . _____ 2 1 a n d e v e r .......... . __________ __________________ T o t a l _____ ____________ 2. 'I'lie exposure time of this series covers a wid range (1-24 years), indicating that type ant intensity of exposure to asbestos as well ai perhaps an individual suseeptihility to asbestoy sis play an important role in determining the development of this pneumoconiosis and thereby tin' possibility of a secondary carcinomatou sequela in the lung. There were 47 males and Id females amon the d2 eases for which information on sex wa available. 'I'lie male: female ratio is thu 2.d:l. which represents a marked shift towa the female ide when compared with the usua sex ratio ol d:l to 10:1 for lung cancers oj unknown etiology. Equalization of carcino genic exposure as represented by asbestosis, foi the two sexes, thus resulted in a trend towart equalization of liability to lung cancer. I It is of importance to note that the me 36 E n v iro n m en ta l C auses o f C aneer o f the Lu . Cansos o f iloulh anion): m alo aslioslos workers oom paroil w illi tilo n io rla lily experience o f all m oil in Kngluiul am i W ales (D oll) ( 'luso o lll'Ul ll X ui ii I>i`r o iloa I lis Xiiinher observo! K.xpcclcl <m Kimlami and Wales ralos Tos of significance of diiroronco bi'l ween olisorvi*d and oxpoolod i value of I'. i espiratory diseases - and eardiovaseular iliseases-- mention of asbestosis. . . ......... .......... out mention of asbostosis........... sms, other th a n hint? cancer . . . r diseases 3----------- --------- - - ......... All c a u se s...................- .............- --------- ------------------- 11 0. s < 0. uuoooi u < 0. 001 if 4 4 : 7. 7 l} >0. 1 ;iu 15. 4 ' <0. 000001 Deluding 1 case w ith pulm onary tuberculosis. Deluding pulm onary tuberculosis. Deluding 2 cases (benign strictu re of esophagus an d septicaem ia) in w hich asbostosis was presen t b u t wa3 night to have been a con trib u to ry cause of d ea th . [ 128 noncomplicalod cases of aslicslosis ,nly 44.2 years (Mercwether). One may ide from this observation that some of individuals apparently died from asbesbefore their lung cancer had a chance to up (Linzbach and Wcdlcr). ditional support for a causal relation jen asbestosis and cancer of the lung is ed from the fact that Mercwether found, ig266 cases of asbestosis observed during 46, 31 cases of coexisting cancer of the ((1.65 percent), while there were 91 cases ing cancer with an average age of 59.4 i among 6,884 cases of silicosis (1.32 peri'/which came to autopsy. Wcdlcr noted bestosis cancer of the lung occurred in net, or 15.2 percent of 92 cases of asbestosis rtuch necropsies were performed, whereas normal rate of lung cancer in autopsy T1 was estimated to be 2-6 percent, into, Yo: aid, Warren, and Cartier are all llceptical as to the actual existence of ttcessive liability of individuals with to lung cancer, and Cureton and $4 ;cr are undecided on this question, iinvestigators, however, favor this eonigr. consider the existence of a causal ttfc-. as highly probable, or established |j|way; Mercwether; Telekv; Xordmann; m Gross; Lecoeur; Smith; Saita; Wcgelin; Ijchand Wedler; Stoll, Bass, and Angrist; oU). pbistological types of lung cancers ob- served do not deviate essentially in their relative frequency from those Siam in cancers of unknown etiology. Then* were 22 squamous carcinomas, 7 oat cell carcinomas, 4 anaplastic carcinomas, and 6 adenocarcinomas. In view of the fact that one of the .Norwegian cases of nickel cancer of the lung was associated with pulmonary sarcoidosis, it may he mentioned that Skavlcin and KitterhoU' reported the combination of an asbestosis with a sarcoidosis of the lung which, however, was not compli cated by a carcinoma. Attempts have been made to refute the claim of a causal relation between asbestosis and lung cancer by determining the frequency of pulmonary cancer among the total worker population of the asbestos industry (Cartier; Yorwald). Such a procedure is hound to give misleading results. It is quite immaterial how many workers employed in the industry develop lung cancer, since an undetermined portion of these workers doubtlessly sustains either no exposure or only a low intensity exposure and thus does not develop asbestosis of the lung, which is the prerequisite for the subsequent cancerous development. Asbestosis must he considered as the essential stigma of an eifective exposure. It is, moreover, iieccenjry to know the sex and age distribution of the worker population studied and evaluated as well as to know the duration of employment and exposure. A marked Labor turnover in the industry is not inducivc for obtaining reliable information on lth Monograph No. 36, 1955 37 llio actual number of lung cancers and ftsbeslosis cases which may result from effective exposures. For lliese reasons, no definite conclusions ran bo drawn from the observation of Cartier, Doling 8 eases of lung cancer among 4,000 workers studied for 10 years, especially as the frequency of asbestosis among effectively exposed workers increases with the duration of exposure (Boliine). Ivennaway and Ivcnuaway re|)orted that. 8 Ivmg cancers may be found among 4,000 males of (lie age range, 45-64 years. The evidence on hand, at any rale, has con vinced the West German Government to make asbestosis cancer of the lung a compen sable disease (Tabershaw). The experimental approach to Ihe problem has so far given equivocal results. Vorwald and Karr, using guinea pigs which were exposed to asbestos dust, obtained negative results. Xordmann and Sorge employed mice for this purpose and claimed (o have produced broucluogenic carcinomas with pulmonary fibrosis in two mice. This observation needs to be con firmed before if can be accepted. iso pu o pvl o ii. Through the recent discovery of cancers of the paranasal sinuses, larynx, and lung among isopropanol manufacturers, the occurrence of carbonpolymer cancers has probably been exextended to man. Isopropyl oil---the crude liquid from winch isopropyl alcohol is distilled and which is a slightly turbid. A'iscous liquid, slowly turning, upon standing, into a brownish to blackish tarry material --contains polypropy lene compounds as well as propylene ether, which may be oxidized into propylene peroxide and propylene epoxide having a tendency to polymerize. Polypropylene, merchandised as Opponol K, is used commercially as an oil for cable filling. Workers employed in isopropanol manufac ture have been exposed to the inhalation of vapors, mist, and dust of isopropyl oil escaping from leaky pipe connections, defective, pumps, and gaskets, or spilled on the floor at the occur rence of breaks in pipelines and during repairs on pipes, pumps, and stills. Weil, Smyth, and Nale reported that, between H)2S and 1950, a total of 7 neoplasms affecting various parts of 38 tin* respiratory tract (nasal sinuses, 4; lai 2; and lung I) came to observation among employees, or in 8.4 percent of those w| worked more than 5 years in the isopropa^ plant. Five additional eases were observed another isopropyl alcohol plant, making a total of 12 eases, 7 of which involved the nas^ sinuses, 4 the larynx, and 1 the lung. It calculated that the incidence rate of cancer of (lie nasal sinuses and larynx for the second group was 134.5 per 100,000, against a normal rale of 0.3, and that the incidence of these can. eers exceeded the expected incidence 21.3 time*.; From the evidence, available it is likely thy these cancers as well as those associated with asbestosis belong to the new class of "polymer cancers." MUSTARD QAS The alleged carcinogenic action of war gy: poisoning figured prominently in the specula, lions as to the cause of the increase in lungcancers observed during the early 1920i (Kikulh; Brockbank; Klotz; Derischanofb Hiinermann; Reiche). Residuals of warfare gassing were noted by Matz in 10 out of 13g cases of pulmonary cancer among Americas! World War I veterans. Four out of 64 casesof lung cancer, recorded by Brockbank, were gassed badly during this war. Macklin noted that war gas poisoning occurred in 5 percent of 164 eases of lung cancer among male*,' while it was present in only 2 percent of soldiers without this disease. Ivoelsch con* ceded that a few cases of lung cancer exhibited a doubtful etiological relation to war gas injury,which was claimed to have caused also two cancels of the larynx (Spnmer; Tilley). No distinction was made at that time as to the particular chemical nature of the various gases used during World War I. These contentions found little acceptance si that time. From a carcinogenic viewpoint, special interest has to be attached to the various arsenic-containing gases, especially Lewisite, and to mustard gas (dichlorcthvl sulfide). The arsenic..'."ur gases, when inhaled, theoretically may not only cause nonspecific chemical damage to the respiratory tissues but also may product there a specific delayed carcinogenic reaction, P In r;i ti. an ni At o'l tin [HI bn cm plo Mi Lt" wo I old poi (V. thecan exp pro V can supj date attc view prod uatn and ruhb briig lati type stud; coini parti systc Up sure tivch siona, act iVi E n viron m en tal C auses o f C ancer o f the LoMft: Public 5*55 - as that scon exceptionally after skin hums ri'jjj these pises. Cancers of such an origin belong l'u' ro"l> <d arsenic cancers. ' V A possible carcinogenic action of mustard upon the bronchial mucosa, on the other b#otl, nlfl.v n>la,ed to its cross-linking and jjdioinknctie eU'eet. and may be identical with 'that demonstrated to exist for experimental "inimals exposed to several sulfur- and nitroustards of aliphatic and aromatic nature. According to the mentioned theoretical con- W*s' ^1C causa^ ve nieehanisin operative, in these cancers resembles in some respects that Possibly active in polymer cancers. During the last few years, three eases of 1JifOnchiogenic carcinoma and 3 eases of larynx ;<jnccr were observed among long-term cm- ; plovees of the Japanese Army Poison Gas Manufacturing Plant on Okuno Island, where Icnisite and Yperite were made. One of these 'orkers was 30 years old and a second, f>3 years Id. All three suffered from chronic war gas ^poisoning due to contact with mustard gas Jr{fcmada, Ilirose, and Miyanishi). In view of observations, the distinct probability of frtreinomatous effects upon the lung following yWposure to mustard gas or chemically related `products deserves serious consideration. Y While the fundamental concept of " polymer Jflliicers" is a tentative one and needs to be iilwpported by additional evidence, the available arc sufficiently important to require serious ^Mention from both a scientific and a practical Ifiewpoint. The rapidly expanding industrial ^production and industrial and general use of -tt'utural and synthetic polymerized substances Atod cross-linking chemicals in plastics, films, jibbers, rosins, adhesives, textiles, and so on. /brings a considerable part of the working popuvhtion into direct contact with chemicals of this !%pe. It seems to be advisable, therefore, to AKody these population groups during the '.Yenning decades for the occurrence of cancers, particularly those affecting the respiratory '.Y*Ttcm. y:- Radioactive Chemicals *b' Up to some 10 years ago, occupational expo- Av'dfcre to radioactive agents was limited to rolaL*bely small groups of industrial and profes- onal workers (miners and refiners of radio active ores, industrial and medical consumers of radioactive substances--gas mantle manu facturers, luminous dial painters, radio tube makers, physicists and (heir assistants, radiolo gists and their assistants). Since the advent of successful atomic fission and the ready produc tion of synthetic radioactive substances, the number and variety of in d iv id u a ls who have occupational contact with radioactive matter have rapidly ami greatly increased (uranium and thorium ore miners, smelter and refinery workers, atomic energy plant employees, mili tary personnel, and agricultural, biological, medical, chemical, metallurgie, oil, pharma ceutical, and other industrial research workers employing radioactive isotopes, as well as operators handling directly or indirectly ma terials or technical devices giving off ionizing radiation, such as radioactive static eliminators (Silson; Berman and Ernest ; Bryan and Silverman), sewage disposal workers, paper and textile manufacturers, and so on. It is an established fact that cancers of the skin, connective tissue, and bone and bloodforming organs have resulted from excessive exposures to radioactive substances affecting the organism or parts of it by various routes. There exists a great deal of highly suggestive, if not conclusive, epidemiological and experi mental evidence relating an occupational in halation of radioactive dust and gases to the development of pulmonary cancers. Although excessive medicinal and occupational exposure to ionizing radiation (radium, X-radiation) alone may produce in man and experimental animals a fibrosis of the lungs (Kalbfleisch; Doenecke; Belt; Bcrgmann and Graham; Engelstad; Warren and Gates; Leach, Farrow, Foote and Wawro; McIntosh; Warren and Spencer; Widmann; Bauer; Bauer and Schraer; Tonges and Kalbfleisch; Frcid and Goldberg), occupational exposure to radioactive dust and gases has often been complicated by simul taneous inhalation of dust containing various metals (chromium, nickel, iron, arsenic, cobalt) as well as silica. Pulmonary cancers observed among radioactive-ore miners, therefore, have V.in complicated in an appreciable number of cases by silicosis of a minor to moderate degree. It is for these reasons that the radioactive genesis of the cancers of the lung noted among these miners as well as among uranium and yffeUie Health Monograph No. 36, 1955 39 radium refinery workers h:is been doubled by some investigators. who fell that. one of the various nonradioaetive metals or the silieosis represented the main causal or an important, contributory agent, (Schinz; Lorenz; Selunorl; Kosloski and .Saupe) o r that the available evi dence did not provide absolute proof of a radio active genesis (Lacassagno). Several investi gators felt that the lung cancers among the radioactive-ore miners in Selmeeherg and Joaehimsthal were principally attributable to a hereditary predisposition created by inbreeding of the mining population (Macklin and Maeklin; Lorenz; Vesin). The "mala metallonun" causing death at. an early age of the miners in the ore mountains of Saxony was first, described by Agricola during the early part, of the 10th century and was sub sequently mentioned by other investigators (Hcnckel; Schedlcr; Thiele). However, it was not until 1870 that its malignant neoplastic, character was correctly recognized (Hailing and Hesse). This judgment was, subsequently confirmed by Coluiheim; Aucko; Arnstein; Ulilig; Rise!; Selunorl; Beyreuther: Rostoski, Saupe and Selunorl; Lange; Neitzel; Dohncrt; Baader; Teleky; Hueck; Rostoski, Saupe, and Selunorl; Thiele; Weber; Ivoelsch; Lindemann; Doubrov; Brandt; Brezina. Although the miners of the uranium ore mines in Joachimsthal (Czechoslovakia) also were suffering from a fatal lung disease similar to that observed among the cobalt ore miners in Sehneeberg, Saxony, it was not until 1020 that the cancerous nature of the pulmonary disease among these miners was recognized (Lowv). Additional confirming evidence was provided later by Beutel and Waldrich; Ziel; Sikl; Saupe; Feller; Pircban and Sikl; Baader; Behounek and Fort; and Teleky. Evidence supporting a radioactive origin of the lung cancers among these two groups of miners was provided by the observation of lung cancers among employees of radium refineries and radium laboratories. Lowy reported the occurrence of two such cases among the workers employed in the laboratories of the Joachiinsthal mines, where the ores are refined and the puri fied material is tested. One of the cases had chronic radiodermatitis, leukemia, and lung cancer. A similar observation was recorded bv Teleky and bv Neitzel in a German technii of a radium laboratory. The cancerous lw was found to be radioactive. Four eases of (mi cancer have recently been observed, accordii to Baader, among the workers employed in tb*,r a d iu m ore processing plant in Belgium, a the. occurrence of such complications was p^/ viously said to be absent (Maisin, citingDelaet):Perhaps the development of a bilateral alveoli carcinoma of the lung in a woman 16 years aft^ the, intravenous injection of 75 ce. ofThoroti may also supply suggestive evidence that W ; cancers may originate from radioactive matoriil used medicinally, when such materials become arrested in the lung. Mention may also be made in this connection of a report of M artland relating the occurrence of cancer in the ethmoid cells in a luminoui'i dial painter, and of two additional cases t*.. ported by Aub, Evans, Ilempelmann, and' Martland. Dial painters not only ingested radioactive material which became deposited in the bones and produced osteogenic sarcomas,' but they also inhaled this m atter which, thu^; may have produced the carcinoma of tin paranasal sinus. di The four cases of cancer of the lung recently? reported in an industrial population at *^# An c not I ;Joha have more o f ai i conti a ra ; ainoi . T1 Schn i twee : of th rang1 incid rocci durii of hi dill 32:! i ering peric rang' gunu in a 400 ! r. 1920 at S< atomic pile site, however, are definitely noli; vean causally related to any specific radioactive ex ally i posurcs sustained by the workers concerned.:; Sclir; In these cases exposure and latent period went T1 iOnnsuftfhiecieontthlyerlohnagndto, ctahuesearlguunmg ecnant ctehra(tLothveen).'? l d1i9e3d9 workers were, in part, not directly concerned,' appr with radioactive material carries little weight; achit Doubtlessly, they had at times environ has mental contact with such a material when th* muni meteorologic conditions were unfavorable for? a t a the ready dispersal of radioactive wastes data this particular operation. M the i In favor of an occupational and radioactive M origin of the lung cancers among the Sehneeberg-, Schn and Joachiinsthal miners is, moreover, the fact; onst; that the excessive liability to pulmonary noo*| have plasia is limited to the workers employed under*,) pass: ground and is absent among the workert$ (Joa* employed aboveground, and among the popula* ; B ela tion at large of Sehneeberg and Joachimsthal,y L ori including the employees of the cobalt pigment- It w plantusingthe Sehneeberg ores (Bauer; Sclimor!).: of p 40 Environm ental Causes o f Cancer o f the h a l PaU excessive lung cancer attack rale, also, has pot been found among the miners of the nearby Georgenstadl region, where the mini's |vc a l0"' radioactivity. There is, further- re, no valid evidence on record that mincis of arsenic-, chromium-, nickel-, and bismuth, (,,ntaining ores are affected by lung cancers at ! ratc even remotely approaching that, seen uflong the two radioactive ore miner groups. The attack rate of lung cancer among the vlineeberg miners has consistently been he- ; ,Tea 75 and 80 percent since 1N79, while that of the Joachimsthul miners has been stated to flll<re from 40 to 50 percent. However, this incidence rate may he too low, considering the rfooiit statement of Bander, who noted that during the period 1900-40, a total of ISO eases of lung cancer were acknowledged as compell able diseases and that in 1929 there were only -23 miners employed at Joachimsthal. Consid ering the fact that the exposure and latent period of lung cancer in Joachimsthal miners ; finies from 10 to 20 years, it may justly he as sumed that these lung cancer eases originated a n miner population of approximately 000 to JflOmembers working at these mines between 1920and 1900. The exposure and latent period tt Sdmccbcrg is stated to vary from If) to 18 rears for the majority of the eases, hut occasionillvto he as short as 7 years (Bander; Rajewsky. sdiraub, and Kahlau). The total number of Sehneeherg miners who died from cancer of the lung between 1879 and 19:i!h according to available records, stands at approximately 400, while th number of Jowhimsthnl miners who fell victim to this disease tas reached 225 (1920-48). An appreciable number of these miners died from lung cancer it a relatively early age as is evident from the data given in table 19 (page 10), which shows Shedefinite shift toward younger age groups. Measurements of the radioactivity of the Sehneeherg and Joachimsthal mines have dom; Mrated that, in both places, mine air and dust i have an excessive degree of radioactivity sur`Passing many times the maximal tolerance dose j. JJoachimstlial 30 times (Feller); Behounek; f Behounek and Fort; Tschelnitz; Ludewig and , Lorenser; Lange; R ajew sky; Stocklasa). , ^ w*is suggested that the recent introduction *f pneumatic drills into these mining opera- lions aggravated the hazard by increasing the production of fine particulate dust containing solid radium. Repealed attempts have been made to pro duce cancers of the respiratory tract in experi mental animals exposed to the, inhalation of radium emanation and/or radioactive mine dust (Solunidtmann; Lowy; Campbell; Dohnert; Kahlau; Rajewsky, Sehraub, and Ivaldau). Sehmidtmaim obtained neither pneumoconiosis nor pulmonary cancer in animals exposed for 2 years to the inhalation of .Sehneeherg mine dust collected from drill holes. Campbell, on the other hand, reported that mice which inhaled dust of Czechoslovak pitchblende displayed a significantly increased number of pulmonary tumors, lu experiments of Dohnert and of Ilucek, mice were placed in cages within the mines. Some mice developed moderate chalicosis, while pulmonary and mediastinal tumors (adenomas, round roll sarcomas), 11 addition to an occasional squamous cell metaplasia of the alveolar epithelium, were seen in an "ab normally" high percentage of the exposed animals. However, the actual number of affect I'd animals was small, and the interpreta tion of the results as to their significance was therefore difficult. Kahlau and Rajewsky, Sehraub, and Kahlau subjected mice to the inhalation of radon. Many of the animals developed bronchial lesions characterized by an atypical epithelial lining as well as by pulmonary adenomas (in 7 of 12 mice of the test series, against 1 in the eont rol series). While they concluded from this evidence that the radioactive origin of lung cancers in Sehneeherg and Joachimsthal miners was confirmed, it seems to be advisable to con sider the evidence obtained by these invest/ gators as highly suggestive, but not conclusive,'< because groat variations in the, incidence rate of lung tumors occur among different groups of mice belonging to noninbrod strains. Additional, mildly suggestive observations have boi'ii reported by Lorenz, Heston, Esehcnbronnor, and Deringer as well as by Henshaw, Riley, and Stapleton. Both groups of investi gators found that mice exposed to ionizing whole body radiation revealed, in addition to leukemia and ovarian tumors, some increase in the number of pulmonary neoplasms. Of hUit Health Monograph No. 36, 1955 41 greater significance in this connedion tire tlie findings of Lisco stmi Finkcl. who found m daphislir and neoplastic proliferations of the. bronchial epithelium in nils inhaling an aerosol of radioactive cerium. Similar results were obtained with plutonium brought into the lungs of rats. Since' uranium ore miners inhale nol only radon and radium dust, hut also uranium, which may he retained in the lungs, llueper, Zitellc, Link, and Johnson injected metallic uranium powder dispersed in lanolin into (he pleural and femoral cavities of rats and obtained sarcomas at, the sites of injection in 13, or 24 percent, of the 54 rats surviving the minimal latent period of (1 months. Evidence thus produced shows that focal accumulations of uranium, which is an alpha-radiation emitter, may exert a eancerigenic action upon the surrounding tissues, hut it docs not.-discriminate between the influence of metal toxicity per se and radioactivity in the genesis of these lesions. From a critical evaluation of the epidemio logical. clinical, and experimental evidence available, it appears that a prolonged inhalation of radioactive gases and/or dust may elicit pulmonary cancers in man (Mart-land; Evans). In commenting on the production of lung cancer by atmospheric carcinogens, an editorial (Lancet, 1952) remarked, "radioactivity of Joaehimsthal mines is stated to be JO times the tolerance dose*. It is scarcely surprising, there fore, that in the past more than half the miners died of lung cancer.'' It stands to reason that this effect on the lungs of workers will prevail wherever similar conditions of exposure to radioactive gases and dust exist. The excessive suicide rate observed in the past among the miners in Joaehimsthal (Sikl) aptly reflects the human misery produced if such hazardous working conditions are permitted to persist. While there thus can be little, if any, doubt of the principal role of ionizing radiation in the production of lung cancers among radioactive ore miners and similarly exposed occupational groups, sonic comments on the possible signi ficance of pneumoconiosis in eliciting or modi fying this effect may be indicated. Reports on the occurrence of pneumoconiosis among the miners in Sclmeeberg and Jonchiinstlial arc contradictory. While Schmorl as well as Rostoski, Sattpe, and .Schinorl in their early reports (11)2(1, 1928) noted that Sdinee miners suffer from more or less intense anf cosilicosis and that this condition was eau, or favoring the development of the bronel cancers, Rostoski and Sattpe stated in 1930 pneumoconiosis was usually not very extent^ in cancerous lungs. Because of the ret slow course of the pulmonary tumors, Rost~ and Sattpe felt that pneumoconiosis may sfoj the intrapulmonary growth of the tumo| Hueck, on the other hand, remarked p silicosis does not represent, a precancerous t dition for the Sclmeeberg lung cancers. Son of the miners had silicosis but not lung , while others had lung cancer b u t not silicosis Similar discrepancies seem to prevail co*, corning Ilit1Joaehimsthal miners. Ziel in 18jj reported that marked silicosis among miners is quite frequent and that ashed lung contain large amounts of silicon oxide. Pirchg and Sikl. on the other hand, maintained that o pneumoconiosis could he found, in spite of abundance of pneumatic drilling, and that pneumoconiosis lias no role in the production the lung cancers. This opinion was shared by Ldwy. Sikh in his most recent communie&tio* on the subject, stated that some degree fibrosis suggestive of silicotic origin could, 4 course, be seen in the cancerous lungs, and that were single cast's of marked silicosis combing with cancer. On the whole, however, silicon^ was not a prominent feature in cases of cancer, on the other hand, the lungs most affected with silieoiibrosis were generally fr from malignant growth. Behounek and Fort noted that pneumoconiosis was recorded u the cause of death in only 8.2 percent of 6S miners who came to autopsy between 1929 ani 1938. This statement contrasts strikingly silk the observations made by Saupe during a, chest X-ray study ;{ 398 Joaehimsthal min conducted in 1939. lvu found that 43.4 percent of these miners presented roentgenologicil. evidence of pulmonary silicosis. However, silicosis was of minor degree among the 1 miners who were suspected of having pul monary neoplasms. ? Although the data are in part contradictory, it seems that silicosis does not play any sig nificant role as a direct or contributory causeof cancer of the lung among the radioactive- 42 Environmental Causes of Cancer of the L*1! piiiicrs in 'clmeeborg and Jonchimslhal. r. Oipthcr it has !U1 antagonistic ell'ccl upon the '"t rjzat,ion process or modifies (lie course of TTostablislied cancer remains proldemal ica.l. finally. it may be mentioned lhat these Inns: peel's vary a. great deal in histological struc- s M ailV wort' scju a m o u s roll c a r c m o m a s ; ^ers, round cell or anaplastic carcinomas; ,^ilc a fc'V were of adenoearcinomatous type. ^ radioactive lung cancers, thus, follow in respect the general pattern set by all her occupational cancers. Yhc rapidly growing production and use of ^jioartive material and the thereby condi- markedly increased exposure of some piled worker groups as well as the, general `^illation to gases, dusts, and mist-s containing pdioactive matter of long half-life doubtlessly presents a potential respiratory cancer hazard serious proportions. The attack rate of Jung rtiieer from such sources is very high, according v past experience with minors of radioactive jffs. Therefore, a competent assessment of &e degree of exposure to atmospheric radioUlivc contaminants for worker groups and yjgkborhood populations of radioactive plants i*l operations, and the continuous and strict jupervision concerning the amounts of radio active effluents emitted from such establish ments, are urgently necessary for safeguarding health of these individuals. T able 20. I,a loti I periods o f en v iro n m en ta l resp ira tory eaneers, io m on th s (Ilucper) (.`aueer of -- Agent Nares and nasal sinuses ; i Average! Itange Average! liange i latent loflatenli latent ioflatent period period period period e lim in a te s ................ N ic k e l.____________ 'f a r fu m es___ . ..... Isopropyl o il. _ ___ Ionizing rad iatio n - ... 18 15 22 Hi 25-35 15-48 5-47 0-30 t) 23 7-50 U 3-20 10 0-10 25 10-32 Intensive studies also are needed for deter mining whether, through radioactive fallouts, the inhalation of highly radioactive dust par ticles diffusely settling in the bronchial mucosa and producing there minute foci of high inten sity radiation may elicit delayed cancerous reactions. Since radiation cancers, like oilier occupational cancers, have a long latent or induction period (table 2(5), it is essential that all possible, precautions be taken against en vironmental contamination with radioactive matter to prevent a possibly permanent con tamination of the human environment with dangerous amounts of radioactive matter. in Comments and Conclusions .d i The comprehensive panoramic view and r* "lysis of the total epidemiological, medical, 'lit tad experimental evidence available on exog.-il toous respiratory carcinomas and carcinogens r. We tin doubt of the fact that not only large rttipational population groups hut also the nl- pneral population have definite and prolonged flfcitaels with one or several of these agents. rv. r For most of these agents, adequate eonelua'- ,*T* proof of their carcinogenicity is provided if to epidemiological, medical, and experimental One of several specific carcinogenic chemicals has been isolated from several agents representing variable chemical mixturesyfsoot, coal tar and pitch, petroleum oils, gasoline and diesel engine exhaust). Wherever a definite identification of a specific causal agent, such as isopropyl oil, asbestos, and chromates, has not yet been attained, the epidemiological evi dence based on an evaluation of cancer inci dence of relatively small, occupationally cir cumscribed total populations at risk is suffi ciently reliable to prove the presence of an occupational respiratory cancer hazard causally ml Health Monograph No. 36, 1955 43 I Vill VVVt vvt to 0|S\ V n. domiological. medical, and experimental data concerning these respiratory carcinogens attest their hirh carcinogenic pnteney muh'r occupa tional conditions, particularly when acting on humans. It is therefore reasonable to assume that inhalation of the same agents, in a miti gated form as air pollutants, by the general population is responsible for a. considerable, portion of the lung cancers attributable to such contacts. If this coherent and logical picture presented by the evidence supporting the various occupa tional respiratory cancers and, ('specially, the coal far fume cancer of the lung, is compared with that available for the cigarette smoke lung cancer, even upon superficial examination, several additional serious defects and inconsis tencies not previously pointed out become' apparent. It is surprising to note the absence of positive statistical associations between lung cancer and cigarette cough, although this latter symptom is clinically characteristic of chronic, chain smokers. Despite the fact that the lips and oral mucosa are constantly bathed in the tarry liquor oozing from the tip of the cigarettes and despite the contact of these parts with the smoke coming from the cigarettes, there' is no consistent statistical association with cancer of these parts. The assertion that no tarry material exudes from the cigarette tip is belied by the evident fact that chronic cigarette, smokers arc observed to have brown-stained lingers. There is, on the other hand, not a single record available of cancer of the fingers attributable to cigarette tar. Such cancers of the, fingers would he equivalent to the numerous cases of coal tar cancers of the hands for which records are available. In an attempt to provide an explanation for this discrepancy in the carcinogenic, behavior between coal tar and cigarette tar, Lickint resorted to the speculative, assumption that cigarette tar possesses a special tissue specificity so that the skin of the first three fingers, although impregnated with cigarette far, is "immune" to its carcinogenic action. It also would be medically unsound to con clude upon a sort of racially conditioned tissue immunity for explaining the observation of *pov.J l tA'H ill l i / d l IliU-bbUUH records of a large Jewish hospital in W Poland, showed a lung cancer frequency percent of all cancers for Jews against a queney of 1o.ti percent for non-Jews, esp in view of the fact, that Eastern Jews are liculurly prone, to develop thromboa obliterans, which has the best cstab' causal relations to tobacco smoking. The. claimed absence of a positive assocr" between lung cancer and the habit of cigarette smoke also is inconsistent ride that the incidence rate of occupa cancers increases with the intensity of ex to a carcinogen. The medical considers! on cigarette smoke cancer of the lung ' reveal a number of serious and fundam defects and contradictions. The best that can be said about the e mental evidence on hand regarding carcino properties of tobacco tar is that it indicates carcinogenic agents in some cigarette . through the use of hyperreactive aj ` There' is no evidence that these observatio the skin of a strain of selectively inbred have any equivalent in man. Thus the lical importance of these observations as cancer of the human lung is at present u tain, especially since Passey, in recent e menls on mice painted for 16 months tobacco tar, was unable to elicit a single of the. skin. Prom these considerations, it is appa that any final decision concerning the rela role of cigarette smoking in the causatio cancer of the human lung should be kep abeyance until a great deal of additional more valid, and especially medically concl evidence becomes available. The data on make it unlikely that cigarette smoking re sen Is a major factor in the production of cancer and in its recent phenomenal frequency. For these reasons, it would be injudicious mainly to base the future preven control of lung cancer hazards on a theo such doubtful scientific merits and to con trate, the immediate epidemiological and e: mental efforts on this apparently overp agandized concept. The apparent wisdo such an attitude is readily apparent from fact that not only a great deal of the cir 44 Environmental Causes o f Cancer o f the 10 ualifti epidemiological evi'i\dience l)iit also ' flftiniUy tl' t'Mtir, factu1anla and conclusive "t'V of ^ Felice available on specific exogcncmis causes "st a Respiratory cancers indicates UI nit those t'specialjT cf,^ are citlior of occupational origin or " are ^ . (3 to industry-related factors. Not only ,0ilIh:iiu [Loccupational groups lint also the members s,ablisli^ j (he general population have contact with eje agents in various forms and intensity. SSOfii||(i f `"I'alir,, with i ' "Palin* u le ra li,,, ung i damnme 1(i exp,-, ciiiog,.,^., etes `t i e i-ir, aniiiii,;. nt ion, red in:, f the pi,,,. US as ly, it nu. <r. t CXp.-fr tllS Will; lo caiii-o ippaiv: ; l'elaiie talion kepi -, mal a:; uelush. on Inn -i g IV[l.-c of lui,; rise m he nit*! veiiliv. leory COlirrll1 experel-propaloin "i om d cirrim;- tic I.uM PWir Health Monograph No. 36, 1V55 Finaliy, it may 1h> noted that the evidence on hand justifies the viewpoint that, in arriving at a judgment (Bander; Liekinl) in any medico legal dispute re(|iiiring the assessment of li ability for the development of a respiratory cancer, any evidence incriminating specific occupational factors should he given preference over that possibly provided by a cigarette smoking history. 45 Bibliography Adler, I.: P rim ary malignant, grow ths of tin* lungs and bronchi. Longmans, (icon & Co.. 1012, p. 30. London. Aldridge, YY'., B arnes, .1., and Denz, F. A.: E x perim ental beryllium poisoning. 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