Document LKJ2XQVYqxQrbkX1NZ6r67Rb3

FILE NAME: ZD^D/ DATE: DOC#: ^D/7 DOCUMENT DESCRIPTION:WWZZ The CancerZZ> \ Ca11adian t:a11eeI" (:011ere nee Yohmu' I Proree<ling;; of the Firl"t Canadian Cmwt'r Researeh ConftrtJlt't' Honey Harhour. Ontario June 16-19. 19."i-l Edited by R. W. BEGG Department of Jfedical R1'search Cnfrcrsity of fllestcrn Ontario London, Canada @ 1955 ACAUK\ffC PRESS l~C.. Pl 'HLISHERS !\'EW YORK.' Y. -~ - -- :/ / -~ / :r .- / .__, or : ~ f .. cc cc ~c::~~~:;. ::::: = c c c R. rr: ~ - i; c ..-t -r- -t' e- , ..... ('J ~ ~ ~ r-1 "I "I H, '..::- Ir, c: _,.. l-... ....,... " -/. -1_ =- 1 ..... /_ "'I I" -r- :r, ~ ;:r; 1', :~ ;::.. ~ -r ,~,7,'ijh-~1;- 1r. I(, I ,,, "' x :..: :._1 ''t "' ':(" 1-~~- "' ~ ~ ~ ~ ~ ~ ~ \r, '::. t~ ;: 5 0 fg 'C:' -c 0 \C -0 ~l \C ""t -r- ""t "'1'" - 0 8-~~(~::t' c553.._C 2 0 g g-.;: sJ, - 0 <''1 0 "-! : ...'.. 0 -i- =- =- " 0 1 ,;, 0 -i- =- ~1r, ~1r, _ 0 ~C. " 01 .. -0 0 ;-5: ::- -- =- .' ;-- --~ -~ ;, t.: :'J ~- ;;; L I. ... ... '' I I ~ ;, '.J .... 2' ._, - ~- --- .;:; - -- .- - - 2 - - - x::::: ::; :,. 9 ;::: ...:,,; ~ ... ~. -- ;:; ,,.~.. :.. __, P. . :..i '~ ~ J. :1. r. "/. ~, '- ..;: -'.._) c -........ ~-g ::: ~~I "'--i tn 00 '> = = "I{-..., "I "I ,,c ~r, oc ~ .... \ JSS II.,, lllTl'LR n1e11ta] air ptil!~:~:~nt:--. '"'lh_~h a .. clu~t:' Cdntai11i11g :--ilil'a, -..cH 1t, :--11H11,t ...;n1i tobacco; d11't' ;;, 1111 ro;u;, t''i'L'Cl:dly a"phalrcd or Pikd road,,; ':-.l:.. \i-t fumes of ga,0111:, Lngine'. irritatin' chemical irnnc,;, y;tpor.;;. and g-:\'b; and war gasc" H< 11n1er. nn detinite or gcncrally :tccepted concJi1,i1111, 1Yere readwJ a,; 111 the rile .,f these agem,;; in tht' production "i ltmg cancers and their ri,;e in frequenc~. It \\'a" not umil the third and fonrth decade of thi" untun- th:n addit1011al well deh!:<e<l uccnpational actil'ities and enYirn11rnc11tal agern;; were again related to thr causation ,,j cancer of the lung and other pan;; fit die respiratory tract: i.e. the na;;al cavity, parana~al sim1'e", and laryn:-.. Among these ad~ition~ tu the li,;t of environmental re;;piratory ca1Kt'r,; 11ere the lung cancer~ among chromate manufacturers ( 1935). of ashcotos \Yorkers ( 1935). of arsenic 11orkt:r,; ( 1930), and of coke 01en operarnr;; (1936), the cance-rs of the nasal caYity, paranasal sinuses. am! Jung amnng coppC'r-nickel smtlter \\orkcrs ( 1932) : the carcinomas of the nasal ;;in11;;e;; among luminous r'!ial paintC'rs ( 1l13 l) : the cancers of the na~al "i11ush. larynx, and hmg a111cmg isopropanol manufacturers ( 19..J.() 1 ; and cancers of the larynx and lung among 11orkers exposed to luhri..:ating oil ~prays or mists (1936, 19+91 (Table III). The most recent and best adnrti~ed addition to this Ji;:t is cigarette smoking. TABLE III. Agent Arsenic Asbestos Chromates Nickel Coal Tar Petroleum oils Isopropyl oil ' ]{adioat._ti\e chemicals Oct1tf:: tiOJitil ~ ite of ca:1cer Lm.g Lung Lm:g Lung nart:~ a11rl na~al :-.intb Lm:g Lung-and laryr: x: Lunglarynx: na:-ai ~inu~ Lur.g na .. d.l '>inu;; Rcsf1raft1r_\' Carcinoqrns and Cai1cos R.-cordt'<i .' '1tniu1 Past 15 Yrars Xun1her of recorded ca' Discon: red ---- ---- - - - --1930 JC134 1932 1932 L'.S..\. Other countrie'i - - - - - - - - - ----------~--. 7 16 22 66 73 63 0 84 0 51 Tutal -")' i--8 i40 1<4 ~I F1.)6 0 3.1 .53 1936 7 .l.l 4(J 1946 1 0 1 4 () 4 6 0 6 foi9 (J (125 t.25 1931 3 () ,) This impressin: evidence on the existence of occnpational and c-111 ;r1111111ental re ...pirat()r:: cancer". hr111e1er, is not gTnerally l'<11hidl'rl'd :1, -,;did 1iy all partic-<> Cf>!l<'<'fne<l with such hazard~. nor i;; tlll'rl' :1m agn< :111 nt or relialJle knm1 krlg-e as to tlw relatiYc role 11hi,h th<''-<' and fltlJ< : , 11- \ I I I{\ l \ \I L \ I \I. I i \ . ' I '\ , ],'-''l \I!"1 .1}1c1Hai agl'Jlt'"' a .......... u111t n1 tht (:t11"',l'-~,~1: 1ir' \';t11.~ r 11( ~ht t--11~-.ll,1r\ tr:.....~- rhu-... the :~iedic~tl d1n{1or ut ;;~1 :1i11rrLt .. l ,!r_tJ11;l:l 1'' \()J111i:lll\- rLc'c::1;_\ t:,]>f'L'>;>td gnat ,],eprici ...111 :t' t ;]i,. ;tnu:tl 111,rit, "i t!it ,t\';1il- al'.t ht;\ <>ll ind11'trial rt''Jirat"n ,;111cT '.1:.1,11-. 1, !lt '1:1tt.!. "f ii:11<' a~ : t'! '.11 ,..,.<' a ,in.~lc nport in till' l1tn;1'.11n 11 h1ch 'I" Ji,art, th:tt tl1" 1n- cir.!c"1<'L' "j lung cancer. and I l'111p!ia,11e thl' \\{)rd 'i:;,idnh'<'.. ;,. l11glll'r i<>: :111\ j>artinil:11 irnl11'1rial g:1-.111p En:: chc :h;.,: ....~, 'l\\'.,. - li:t\t <>1111 ;.b,_,\1n ;in i11crea.;;ed rl'lati1e fr,qiwnl'Y i 1ung ca:ictr. :111<1 )wnc, l frd th:tc until inciclc11ce ,tndies ha\'e lwtn d<>l!L'. 11c ha.J ittt,r ,1a1 a11:l\ in !!l cn1111nenting aho11t lung cancer-: in i11d11,trial 11urkcr,..." 1':t1alkling thi.; CtlC'goriraI attack 011 the .;ig11i1],-;111u: 'if indu,tn-niatl'rl <'ll\1n1nnw1nal and occl!patiunal ial'tor.;; in the ra11,ati..n "i n:,;pir:1t"ry ca1:cer,.. i.;; the recent challl'~Jge prc.;;ent('(l ),: the pr 'l"-''wnt~ of the ,i,g:ucttt- >Jnnking the,1r_1 of lung cancer gc1w.;i,;. It i" alleged by tlk,t' i111e.;tigatr1rs. on the basio, ui "tati,.,tical C' ;dence. that t!w gTcat majnnty ut lur;s L:uJCer,.,-i.e. up to l)()r~--nhsernd during- tlw Ja..;t 30 year,;, a;; ll'cll as !he n:cent rapid ri;;e in lung cancer ircqnenc~. are attnl1utable t" cigarette smoking and the increase in thi,; habit. n-.;pccti\'el_1 (Table I\. 1. T .~BL E 1\ ~. Statisfi('a/ (~orrclatin11s JJct1.t't't...ll 'Tu=iu.L-(0 .')1,. ,-.J:ii:,7 and 1-u.1; 7 ( Li!'L 1~r x . ------D-e-g-re-e-o-i -S-m-o-ki-ng Habit Among Lung Cui<:er Patient- 1 ~f alt-, 1 Highly \'ery .-1 -\ _;: il)r:.. exce .. ..,j' e heavy He;i,y ~foderi!!e c.rn.,kers ,;-.. \._ : . :- t: ~'"\,_ <'f a!. (156) \ \: "'kr and <;raham (187) !Joi'. and llill 142) Hre .. ~. 1\\' 1'! al (_;~t: : I 1)-i) ( 24) c,),_~,, ,t'y \\'ynkr and Craham JJ.,: ! and Hill Jlr,.,;,,\,. <"I a!. 11' 3 20 3 30 13.3 ,\(),1) 7 t) 21 3.5 50 (J 30.9 3; 2 21 () .vu _;q 7 19 ' ,\; () 21 () 11.5 .'t; f) 114 3() 5 14.8 rn ~ 12 2 124 .'.xf', ,) 5 111:: ',)() ~71 111 Cigarette ..... (iJ1Jy, };,i]aJh'C ;1i1i_- ;l 1 ~d <i f!ar .. 1-lG 1 3 ~ l (/(I 2 (J 14.li ~~.B .l<U Tlw ,.J11ir111s i111pn,,,i"11 i.; produced by th.-,t iar nad1ing claillls that an elilli11.ttiun of the cigart'tlt' -,n111ki11g hal,it "' 11nld n-ilt. 1\itl1in J .::. 30 :<::r-. l!l a rl'd1wti11n oi the llllllll)('r 1Jf Jun~ c;u1n-r-, trJ a kn:l ]>r<1:iili11glwi11:,. tlw t11n1 of thl' nntur_\ and tlw ;uil-,nt <Ji t!w 1i~:1r"tt". :"!:1<: dw t\10 Jlr<')"''iti>Ib <Jutli1wd )"'""" :ulll<'r<nt' ,,i 1'1lh<'J1i"ll''" ;in,: .,:-. ;wti1tI> anrl 11gr<1u ...J_1 propag.tttd in i1<itli tlw ,,in1t111, and la1 I <i() II. l. llll.1'11' pres~. the:: dt-...t rrc ...,t_Tic l~"' ((111:--i\r:tti(ln '"I ht_' ~u.:ctpl;lll(l' oi either .t ,,j- hoth rii tlH,t :l'kg:1ti11,.. is hn1111d to ("-;en a profounrl 11ifli1t11rc :11 " :h< dircdin which ihe c.:mrr.,] of rc.;pirat"r_1 caliccr ha1<1nJ, 11ill lian : ,.,:,c 111 the i111t11edi.t;c iut1:n. a.;; 11:ll ;i.; 11pn11 the type ()i q1<k111iol<1gi, .:l'.1 C\]ll'rinwntal n,tarch 11.rk 11hich slitiulrl hl' 1mdC'rtakcn 11 1Jii, ,..;;i.;n... 1 0 , - - - - - - during the n.rning _near~. .\pan frrnn thl' not 1mimpo1 iant 111:1ttt-r "; ,..c1e11tiJic accur:ic: and 1 :1lidit: of the~e claims. the~ ;i],..o po;;(' medic kg.,: illlp1Katill1' of no mean pro1ortH1no;, 11liich arc of inm1ediatc COIKtTn l< panic~ engaged in the pro,,ec1nion <tJl(l adjudication of co!l1.Jl('!l':ni11~ claim'. . \ crir:c;1] and ,..niJer an:dysi~ of the e\iclcncc ;nailablc ': the c111qtion of rc~pirat(lry cane<:rs by e1wirunmental ag-tms therefun ;,1pcar~ to he ni ,r:1mL imj>' 1rta11ce and urg-cncy for thc;;e rca"<m:,. :.in i c'pecially in yiew of tl1e ccntinued alarming ancl prugres~i\'(: rise in canur.c of the lung in all industrialized countries (Fig. l 1. 9 ENMGhlL..A.t~:S.JD WA~ES ~'. USA ,t..-ES PJ.;..', / I _Es I I !"\ r..; r Ii 6 t.,CF.':AY t"'EN.C.LES I . I 5 .. 3 2 E~~~1~~~t ~-J--~t S - < .,,.:;; .--:_--_ -~, '') -- --~~"1..,..~t.J ___ ...... _ .. _ ...... - : - ..---~;:.._..._~ u.:::.A FEMALES FEMALES 0 1924 192!1 1932 :936 1940 1944 1940 1<;:0 Fu l._ ('1; ... p,1ratl\l' !r\'JHJ, ii. r1.. .. p1r.tt111_\. 1.1111t1 11Hwt.ii1t~ !'12..J-i<,_.:::,, 1\.\ lli<IC\ \Jr\. I \I l '- ' ' , r ~ .... J'IJ '" l 'rr1u1u,\-/1n1!1ul 'l'idi'Jl(t' ;(1:r11u;,,i _J;. __ i ~ 111,, ;, (.ti;;< -( i '!f,\',,l',"1l)[ !. :r n .\111u11g tl1c ,-ario11-.. 1dht'r\~ttl11!1-... L':.\''~~:~ ... t.~~\1~:i~nitn1:tl tir1gn1 j11 n.-...p1r:tt11r_\ canc~T ... and n .... r1 ... c 1!1 :--t ,:: .. 111.._\-. ~ ~ :.. : t' :.1' I'" c 1l (, 1 1h, marhvd \";1riat1rn1~ 111 tliL tinw oi (lll'll ,,: tlw -~ttttr 11}lt'l11Jnt..11(1Jl. 1n lT' i11ten:--it\ ;n1d in it:-:. pn1~rt""'""'H111 in dl1:1 r i1t 1.:\' --1n(-. -...1:11t ...... 111i 1\ i n c l - . c'flll!ltil'~. ngHll~. and co11111111nitil'' 1 T:d 0!,' \ ... n.J \ "l. Fi.2 ..? \\ liik I'\ !:LI \- /_// 111/ l 'tJi:c( J" f lt\If h /\'(: ( .1 in 1<1.;,,) .n~ (",11Jc n((1th /':11!, '\', , ,.: ' r- ). /f/I 111' ,1 -..,. p :State lonncct1nll 111inoi< \I ar) land .\I a"acht1'ett< \lichigan :\t:w Ha111p<i111 e :\<:\1 Jc1-cy :\t:\\' \-,,..1, Ohio Penn.;;,} h a111a !~bode J,Jand I ndusni(u z::1'1_f J(l..j6 "I..~ -~..., ~ 1 f)::; 10.+ 57 / .j Q/ Hl.2 (,.(; (, 7 k i '': : :t.r Florida J. . 11uii..,1ana .\l J"(JlJri .\lnl\ta11a .\' dira-ka .\'f11frs 7.i.'ith f(r<nnnal (, k fi _; 73 1() 0 :-. 7 huf11 \tnai::iJ:1.~.i; .\ lahaina _\,~k~111"d" :\('\\ \l<--.;1,0 .\'ortl1 Can,lina .\'orth l>~k11ta Uregun :-'outh Carolina \ \r a-..hing ton \\'j Dtlllllg- . loncu!turoi +o .) (, zr, 3 I :;f, + 1 ,) () :: l 4 'I , !1!: - 1 :\1111. ''H ll \_\, The d(ath r.itt..., Ji ,r t J a lJ, ]'J-f'J, l ,i!ri ( 1 ! lt,l\11 , .. : t ~rr ]<1~(/ ','.I f'i \ .; ,( ~ t ' J I )' 1 , t ' Lt <I ,, !;!iJt" i1i1 ii: \(',l.1. } 1J~S \\ t It ; 1r,. !1:, t, J : ,\ :',i ~ ; .. ; L I, .f 11L..J.;---: 111 x ) x .j lfl 2 7 1 1(J 1 II/ l I.() / .) x .j i+ 7 4 ;-:, __"Z. ()_.j (~ ~ xo 1 .j (J -l n n ..f.j :: I .+.? ~ () \ 1) ~ l 1( ;t', ( I "'~, .. L' ' !, I : ..._. ~ ' { ! .. ' . J<il \\. l Ill I !"I.I( in \"or11;11, It',.,, 1han ,,,; .,f :tll c:u1ctT:' i11 lllale~ i11nih-e tlw Jung-. die co1Tc,pu1H!1:1g :::.._\ff(;, r t;nat Britain i,; al1,l11t 2.;'.;.. The n11,et ni the ri't' in l1111g c:inn-r 11Ln:i'.:t1 JCJ.?.': lnng did lll>t ucn!l" 111 Italy until ahom J<l30 ( J<IJO- l;1n,: :1u:. p:<y rate nf :tll atllup,ie' in l':t<ltn and .\lil:tn 0.t)/ l)z 1111.1r> <(x rf \l:l 1 \"l. . , ,1at1;,( .17 ]\1tsfuafury l_"t111Ci~r. }(,13,- and Jt)/i J/ "1e'1r. I;:,1;t'.\ t1 1: .\'u1( .1ftfr(1f1,1!1lan CL'1l(i'J'S, !'.\' /',T J()(1,011(} Potuld/111111 -..itt a11(l city I'l31 \f <1k Perl"en t 10~7 lr~1.n.:a . . e I (/37 Fen1aJe:-. Percnit Jt147 i11crca'e J<J3/ Atl,wta :'\e11 Orlt'an, Dalla; n1r111111gl1.t111 I >em er 5an Franchcv Chicago Pitt,hurgh Dttroit :'J) 13.1 3.l./ -! :; 9.1 15.6 - l.U (./. / 12.6 13 4 391 nr(i}/(/1111 ,uul l..uno 168 1.0 .=; 0 -!00 198 28 ..f.2 50 "' !.'111 392 OS 6-! 1180 11' 1) 320 2.1 .) 'I 86 21 <i HJ -t.2 KI 93 3-t 3 120 3.<! S 1 !OX 29.3 122 4.3 70 63 26.I 16'J H ..... 12 32.0 154 2..3 _;.i l-t8 A.ti an ta X ew Urka::< Dalla< Birmingham Demer San Fran.:i:-.co Chicago Pittsburgh Detroit - L1.1ryn.r IA -!.O 1~6 03 0.3 JU 149 '')~ 0-t I 0 150 ~.2 .) 3 r,6 1.5 0 -t 73 IA -!.O 1~6 0.0 l 3 20 -! I 105 00 0.0 -t:; RK 96 () 2 O.~ 300 67 7.0 -t 0.4 06 50 -!A 8 (j 82 04 0.8 100 ',),;:"! 6A R3 0.4 0.3 -2~ an10metrin Senion Xati:.nal Cancer In<titute 29 i.6 3.1 .u 66 98 8 ::-: 73 7.6 0.9 5 6 2.3 07 0.9 2-! 3 5 2A 2.0 T1.tal J0-!7 ~.C/ 20.8 17 2 11 0 1-!.8 21) 8 18 0 15 6 j')IJ 20 76 27 2.6 20 -!.6 37 H 3A Prn.t..'l1t inci-e;i-..c- 20;li-t .i;:; 2.n 12-! 112 103 114 l.'O 122 '6 17 271 122 92 6 83 70 and 0.13;,;.; )~121-:l--193.S in Yrnice (J.5~,; 1. The rise in lung cancer mortality lagg-erl in rural 1Ji,tricts of Denmark hy ten years behind that of Copenhagen. Stocks f 1<>-+ 1 found that the local incidence rates of hmg cancer in England and \\"ale~ during _fCYealed a general relationship 1921 and J939, and 19-t() and 1948, ,L, n.pre~~ions 01 atmospht-ric to the' l'xtent and dPn<:ity nf air pollution through ~mokc llllil! np arc.;, < Talile \' l I J. Similar r,l ,~en-atir m" were reported for frolll chinmcys E11gla11d and \ \"aln by J(e1maway and Kenna way i 9(>) covering the period Jl).j.(j Jl)-l<J, and C'fJJllparing luni; cncer !ll<irtality ra((.;; oi Cr<'att'r London with tliri-c ()i br.l_!l'r 10\\"lh and ni ral di .;t rich ( Talik \ 11 r I. Th(' d iologic -,iglllficancc MINING RANCHING ' I ' ' ,,, f'\\!R(l\\fl:'\I \f. '\I. 1 1.... ' )---. INDUSTRY L , ll~GC:IC.J ~ ~ ,,LJ,c r JI DEATH RATE ALL CANCERS- 147 PER 100,000 SKIN-IS RESPIRATORY-32 DEATH RATE ALL CA';C(R.S-20 0 PER 100,000 SKIN-I!> ESPIRATORY- 50 DEA.TH RATE ALL CANCERS - !~ PER IOO, 000 SKIN-18 RESPIPATORY-30 COLORADd - 194~ - ~g49 J FiG. 2. :-;pcc1tic e<rnc, r ,:,atl> .:: niaJe, iii the~c cpirle111iologictl li11<li11g-,: i-; inr!ic;1:cri L: ;;,c- rn:nt iicll><JILtratinn of 3..+-lienzpyrenc in the pollutants \\"aller ( 180). and of the of the air ,,f nTr;il En1.::li~h citic-' !.<;. lC'falaiff.orin<ij<a).. J(a)u()dI. of the n:hapuaqrtitcJfulgaate'>(Jplhinae-;ea11r,df tdhiehdaireno~iinrfhj' IA:\ngJ-(trl.eti-n;, 'fAHLE \~Il. Ltlll(/ Cantt'r Jlorl11fity Idd f);f:.:!ut1011 (,n,111,, of adjacent to1111' 01er .2(1(1.(l(J() (Jl'Cllj11cd d\\Clling"i 1.ondoJJ and -"11l,mh;i1J .\na J:irllli11gha111 ;p1d .',11hnrli;1n \n" :>.r .u1chhter and :;uln1rha11 . \n-.1 .;;;Jwt1idd 11 <ti! l.i1erpool aJJd :\uliurloan An;, J.l'cd, and :-;uburlia11 _\ na l.?1,0011 ll llJ>!('d d1HJl111g-: .\t-1\< .i-tk \ggregatl' \ggng.tte \cgn.t:;ltt \gg?q!att \f!gi"(l',:11( '' h' ( r~( rt 1!l ;rnd ( ui f1 of .) pf 1.! 1;f J.~ 11f .!ji '( ! t1~ ;,tlt,Jiead 111th l".7,0110 f(l\\Ih \\itf1 SOnfJq t'J to\Uh \\1: 11 ~lJ.0110 111 i1\ui-. \\l!lr .~(l.f1u(1 tiJ t<1\\iJ-. \\lt]l 2f),(1(jjJ l!I !11\\JJ ... \\1tlr 1<..., .. tJ,an '"" upi<'d 'i ,.-]j J.~ :<_==iJUJfJ 111': :;j,;,,l ,;,\1 :;liq! ... _::fJ,000 r1ccu~1it<i d\\( ~;lll~..., -ll),<JfH> ll('t ;r111 d '~\'. ,_J}inJ.!' ,)!1,()()(/ t>-11 llj"t'J ;\\ ;/J,}..! ... 211.fH,(J ''' ll:J''11: .J!JJ._1-. flc~urif\'1 I .'r', 1.'-i 15'1 u.2"-I ') ,_ 1,),"' ll 4 11 3 ! ui' 1 n-t !i111 '' J l'i-f 11. l. 11 l El'ER T.1rn r \ iii , ,r1h ,, ,1r ,_111.!J Lll:J J_,:r.uz.r .. hn_q!and (11/(i fl',t!1,1i !Olo - JO/u Type ut \.',tJ1lfl!U11J t} ( ;re.ttcr l.t \rlll, ., l C (unt,: h ir( 111 ..:f' Other ur li,rn ,;; <r.. ,1' Hural tl1-'r,r- 11 J\.cf<.rl IlCl' ,-i,). 1.tlllg C<lI1Cl'r rd.un-nurnh::.r of pcr:-ipn.;. ;1r\ du1.:i11~ one Jt.ath :\lak, Female,; ll!O 100 L'.'I 137 160 136 _) ,"....) 18~; Laryllx ca!lcer r.1tio-11umher of pt1,,,.;, pr~1duci11g- t111e dea~lt :\I ale, Female.; 100 1011 p~ ."':i 1.\k 30 170 42 This irngubr epiJennulugic pattern exhiliite<l Ii:; lu11g cancer~ for <lifferem re~ion, anJ population groups conforms more closely with that sho11 n by induqrial de\eloprnents than with one \rhich might he expected :t:-- the re-;ult of a carcinogenic action of a ,;ingle environment:il factor, ,;uch a~ cigarette .:;moking. This i11terprt'l;it1on of the data un the general epidemiologic beha Yiur of lnng cancer is suppurted by e\idence on hand on the frequency ui these tumor~ a:nrmg members of special occupational groups. for some which \H'll def. nee! <ex.ogt nou:-; carcinogenic cont;ict~ :He known to exist \Tables IX-XII l. T.\HLE IX. L:u::1 Ca11ccr J!,,11h Hate p,r l,1JOI) J)c,1ths of_!/! Causes for )c<c11 Jnd11stri,zl Gro~1;-s 111 0/11,,, 19.J7, ,-J111011g 5,309 Jlale C.111ccr Deaths" Industry Iron and >tet:l Transportation Agriculture Hubher and pJa,tio ~tone, clay, gla~~ ".:\' un-icrr(JU-.. rneta: :\1 mmg and (jUarr: i11g Total aReferencc 118. Re,piratory cancer 2.18 2.<Jl 0.82 2.34 0.66 3.22 1.5.\ 1.71) Operating railroad workers inhale carcinogenic polycvclic lwdrocarhon~ contained in the sooty exhau~t oi die-,el engines aml coal and oil lmrnin;.; locomotiyes. The employnwnt ratio of operating railroad wor-l.;1rs w~h l :4. Thus ahout 75':-i- oi the lung cancers occurred among the opt-rating group repre:,entmg about 25':'~ oi the total numbc-r of empl<>_\T<'S. J{oss ( 147) recently stated that tlwn: occurred during the pniod l <J.).) to 1952 an alrn()-;t tenfold increa'ie in the relative frl'q11cncy of death from J-:\.l.IR<>"\\11..\ I \l ~\ t 1 I \ \ ) /..: )'15 ..:: - ~~ . ~ ::: :... ;, ~ ..-: ::: ::: ..,. h ::: r, Y.. -r --,. : ::: ::. "::r ..-'J ~ / -0.:;.-:. 2. ,_ ...::: I ::: I ~ '..::. ol :... - 21" ~ - ! -~ -: :.. ! ...--: - -, Y.. ::: 'J .I, -:: --:::: 1 -,f'-::: -:: / .2 -;::.:. / :; 3 ii-. 'J Y.. :_, "' ::: -:: ...: .2 "- _, .;: .r, "' ;..., -l Of :.. I :., ~ r ; / ::; x. ::::-:: :.. ;.-.: "- ::: 'I tr. ::; "- ::.. - .;"::- ~ :.. .... :=: -, "-, ....; .. :.. / ..-: - / :... ...'::: - ~ ;~ "- :.. :I :.... '- ,. - ~ C' :! :... :_, :... =.::: --. - _}~ -= ..-: 7 ~ 3 " " ~ ~ t .... ...... . :.. "' .=: 1 -: /. ' :.. ' r - ~~ :., :;- --, z. - - / ~ 1()(1 I\.<. lll'EJ'll< ~f.\HI.r :\.I. J,ru.-; l-1lnti~f J.,,;1.,1: . _\ Ha.ilr()ad l'tno-1 Tut t; r~'~) h111g c.~!Kt'l" .-\ JC>-tO-J0."11 ); H 1<l39-1 <l...jQ I0-1- ./m11;11 <>ft'ratuur dnd _\',1/1)f'1Tatu1u ,1\'d .'rillJJ f I ,11 !..-rs Lung Lancer.., r.ung- cancer< Lun![ c.1.:~\..-t"'r~ OJH:rat!ng 1\ R "<>rker< .'.'\t). ,..,~ .?4 K3 S9 57 :h)tl<'pcrating RR wurkers .\:o. % ' 17 15 14 11rnlett-:-!11111et! RR \\,,-l..tr,; }Jo. <(. 30 21..) lung- cannr arrn.:1g the memht'r,; rJf the Bnlthcrhood of Ibilroad Train- lJ1('l1. Dunner and Jf icks i -t.5 i recently called attentiun to two additiuna! sptTific worker groups, narnt:!y boiler scalers and grain dockers. whi) seemed to ha\e ;in exces5i\e liability to ltmg cancer. It ma\ he po;;:;ible that contact with chromate containing scale. if chromates are used as antirusting agents, may account for the oh-.,ervations of boiler ~caler,;. The presence of fungicides or other chemical additins or contaminanb may have to be cons irlered in relation to the lung cancer liability of grain doch:rs. Co11cl11si1t J::zid<'llCC on Em.'iro1w1cntaf Rrsfircifory Carci11or_;c11s The demonstra.1ion of -;pecial lung cancer hazards produced by a number of \Yell definf'd e:-:ogenous chemical or physical carcinogens has so far l .er;1 achieved for oni,:. relati\ely small and circumscribed \\'Orker gronp:.: It is well recognized, ho\\'e\'er, that similar contacts exist for other and riften Yery large industrial groups \\hich either ha\'e as >et not been ~untycd or about which records c,f imestigations undertaken in the past an: rn,t available in publ-islied form. Since many of the occupational re~piratory cancer hazards e:-:tend in snme furm and to some deg-ree to the general population throu~h contact \\'ith indu"tria! waste<. rekascd into the atmosphere, with gasoline and die-,el engine exhaust, dust from tarn-<! ;mcl oiled roads, and the ah1asion of rubber tires, or the handling ancl u-e rif consumer go(Jds (paint". ~prays. anti rusting agents), it can jmtly hlconcluded that ti it actual scope of the e1n-iron111e11tal respiratory cancer 1 problem may be r:.if a 111agnit11de uni;; faintly <lic:cernihle from the recr1rcled .: faf'tmd rvid1ncf'. General Characteristics of Environmental Lung Cancers .\n analysi-; <Ji the epidemi()Jc,gic and sym11tomatic data on \'tffironmental respirator] cancer-; ~h111\c: that these IH'npla~rns as a g:rcn;J, li;1\1 certain g('1wral d:i:tracteri-tiC'' /'.xf'os11r<' Tiui,: and l.11/e1,/ l'c-riod. In tlw ma1orit1 t1f 11l'!'\l] >;tt;, nal 1-.\\ ]!{1>\,_\ll '> 1 \I. I I .\1, , ''-< !R ) ll,- ~ ~ "'- -t "".:(: ....... l - - .::: Sr . . :.c :.c 1r. ""l .-~ ~- ~ g ,, - -- . :-~~-S-;: :.<'. f - ~)&~~~ ...., .. l-. 2 ~ -;:: ~ - - - -;. ! ;,, ~:.,., ~ =>".: x~, ~ E :.I'.. ~. ;-: ~ ~ "I -r = .:: :::: 2 L.. 1!" ~ =- - "- ~ 1r, ~ -" - i j ~ 3.0 ~ .~ ~ ..- ,.., . ..'.::; ! :L'. .:;; ~ '- .... ..;:: .....: - - ..::; :,, J.. =!.. -r h x = ~~-~~ ~ ,5 ---- t: ~ '- ~- ": ~ -r :;:--. :-: ~.:; -:: ~ """ '!.> - ,;; =_, . - ~ ~ ..~- ~ '"'' :.,. -~ j~ ~ L.. - ;: ~.~'~ ~ ~ ':L .r. :.:.:: :- ;:::: "-'. ......: ~ .- r': :-.:r. .r. 2 ;J :: "' :..:..: .~ -~ rd t -::= c ~ -E C ~ ~ :E_ ~!~ ~ f '- t --:; ~ ..-; ~ '.t :.c ,.f c: ~ -~ f f f ~ ,.-.... - ;-' .r -:::: .~ - ~ f ': J. ~ -. - - - =~ ~ ~ ...-: .-!. .E ~ -; :f.. - '"' "": ~ ~ _:! ;.. . :I f f. - f - ...:... "-::: :.r -,,, ",..., JJ -: ") ~, .L 2 ~ .....-: -;: x tr,::-,.-.~ - lr~ - :..0:: J :c ~ = - ~ ';=; ~ ; I ;:: "' t; .,...; ' ::: ...... ' ~ ,_, 15 Ii... I .2 .~ -;:: 0 f i 2: ~ E f ....; ~ ~ -~ ..~"23 ; f. 2 -3 ? ~ :l_ I ;: 3 - - ~~ ::! ;. r1:ii~~~-:~<~ -~ :: ~-:::: j ",. ~ 2 ,.:, ;:: ; .~ -'_, :J ~: ? (_ -- ...; - :,... ~ t; ~ ~~g _, :. - - t; .... :.. f :..... - ._,;: - ,. " .J'. ' :. - -- J<I~ \\ l. 11 l l"l'F1' rL:;pirall1n c-:u1le>. rh, d1,.;ea''-' 1,.; d1"c0Yerecl \\'hile tlic mdi1idu:d i~ :otil! at work: i e. tlK ,:':!'"''tir<' ti111c 3.;; i<kntical \1ith the latent p('riod. lluw (1er, there e"i'> :-cl1:1hle nid,nce gathered frnrn the entire uccupatinnai c;i.ncer field 11 h1cl1 1r,1ve- that the exposure ti1rn: 111:t1 h1 much ,Jiurttr than the latent jc~:. .... l Thnei<r<:. an l'n1iru11mern:1l l11ng c<11JCn lllay become n1anifr:;t J11a ny yc-:i.rs aitcr expo;;urt' to a o;1wcit]c exogcnot1' agent ha-. ceased . . \n an:1h:'1:' "i the fin:i.1 hte of .;;nnw i_;n inrnwr chrn111:otc 11nrkcrcngaged in chrom.:ite production for at least ~ix month-;. and haYing pas~ed a latent period ui :11C1re than fuur year-; after di,continuation oi their ernplO}lllent, demon,tratt-.i that of 25 deaths 11hich han: so far occurred in thi~ group, fiye \\Ge caused by cancer of the respiratory tract represenrmg 20% of death,, irn:n :-ill cause;;. In a-;bestosi,; luug cancer the exposttre-Jree inter val ranged frum ~everal mnnths to 20 years in many cases ( 182). From the iniorrnatinn aYai!ahle on the length of latent periods for the different types oi emironmental r<"spiratory cancers. Tables XIII and XI\r were prepared \\hich show the interrelations between exposure period and latent p~riorl. as well as the years which mnally elapse between the onset of expo' ure and the manifestation of the canc<"'r resulting therefrom. .1ttark Rates. The information arnilable on the attack rates of the T \HIE xrrr. /..il<..t f\'l"J"'is o.f r:11; l/"f>!/11/('l/fai Nsrirator_\' Ca11ccrs Lung >:arc.; and na:--al ~inu"es .\.'er age Jfange oi .\n:rage latent latent .\ -bt',l<b .-\g~nt !'e1r8ind p1e5r-i-o4d8 -----------~--------~--- - - - latent period -- -- Chromate' 15 _;_17 .'\1ckel 22 6-30 11 Tar fume' 16 9-23 I ,opropyl oil - - ]() Io11iLi11g- radiation 25-3.l 7 .)0 r -.1 1'Perio<l expre-....,ed J!l yc<.1r:--. Range oi latent period :l-26 6 l(i l'J-32 T \HLE XI\'. _\g-cnt [: 1-f11 ,11r1' --------- -- ----\ ,]1e .. to .. \1d....1 _.\":rage t".\ :.><> ... Ur: -:_ n1c --~-- JJ.l ~ t) l:C i;'f llll\.' <'XjJfl'-..-.,('d l!l ' t.,tr"' Ti111(r f,Ullg rir J:w:11011111,11/a.' Hang..- of c;xpo .. urc lltlll' 110 -1(1 mafe, 11 .~--IX i<-maJ,, 1 -:;,~ Jl 1,tlc-., NL,f'ud/or1 .\'an, all(! .\ \Trage expo~un: tune 23 (~all<t'rs na>al ,11111>t, I~a11ge of l'XJH,,,,,llr(' t 111 lt..~ 3-2f> I-..,\ 11~11"\ \ I I " \ ! ' \ ! 11 \<, \>.I I~ J'l'I \a111n1:;. t'tl\'tn1n111ctnal n_-...jllLlltP-_\ ca11cv1:-. f();- :!:~ 1hip11LL:1(r:1_... ~it ri:---1-. 1-... dcf1cri1v and l!l:t\'l'ltr;1te. with the P""1J,], t \.cv;ltl('!l ti !he data 011 rc''pir:it1iry canc,r, :urning chr1111att 111:i11ut:1c:11rcT'. l"'l'ni1._1J ak<ilH>I maker' and rad111alt11T !l!'l' miner". Th\' nid,:;,'c 111 hand !1 ,,:tack ratt" i,ir the 1arion" occupational re,piratory cancer,;. 111<11-conT. i~ expre,;-;cd in tcrnb 11hich cannot readil_1 he hro11_ght np"11 ;, nn1111"'1 der'ciminatrn In naluating the merits oi these estimate". con:'1dcratiou. mnrecJ\er, mti.'1 he gin1t to the fact that the attack rate;; an ,;llh_itn tn ,-;i.ri"u,; factors. ,uch ;t" the relat11t JH1tc11c_1 oi a particular carcm<>.~cn. the n11en:--1t~ a11rl d11ration .lf expo--11n'. and the accuracy and complc-tene'' r i ren1rds kept <"'S]ll'lially in regard to forrner workers who left ha7.anluu' "JllTaticJ!l" The attack rate,;, theniClre. ma~ yar_1 11 ith different grc.up, ex110,erl t" the qm1 ctrc1 nogen. The data gircn in Table :'\\~, therefore. sh(1uld lie regarded as rough approxiniations dbignating the magnitude of trend,.. in cancer frequency for ,;pecial population group:s exposed to sc\eral p~1rtin1lar occupational carci11ogens, rathc-r than exact ya!ues of incidence. or frequency of respiratory cancers These attack rates obtained on s1,ecial 1\orker groups. how(1cr-. are not appl ica!Jle to any other \1orkcr group 1d1ich might tJe exposed tu tl1e same agents, nor to the general population 1d1ich ha;; act1Ye respiratir~- contact with some of them in a mitigated forr:i. . I!f<' and Sc.1 /Jistrilmtiun. ( kcupational re~111r;d(Jry G1ncn, ,,ften follnw the general Iiattern (Ji occupational cancers Ly exh1lJitmg a trend toward a ,,Jiiit to : <1nnger age groups than thoo.e chan.cteristic for crypto.t:endic canrer' <ii the re,piratory organ:-.. It '"'-'llh that tl1c ag-c- at fJ!l::.l'l oi t."\p<i--ure a' 11tll a, the l!lten,;ity and duratl!J!l <Ji e''jJiJ-,ure m addition 10 the 111ite11cy of the carcinogen account for thi-. pl1uHJ111erHJ1l (Tal1k .\:\'J ). _\ cl1aracteri..;tic and sig nilicant ~hi ft in a~e di .._tri lmt I< 111 1Ji occupational re.;pirat!)ry cancers i,; dern11n,trable for Inn>-'. r;uKr:r..; pr1Jrlt1ctd I11 chnrnw pigrncnb, tar iurne,. and ionizing radiation. The grl'at majority of occupational re,pirat11ry ctnct.T~ rec<Jn!ed m'"hcd maJc,, hecathc mly rnak-, 1\ere (1npl11ycd in the hzuardPth JCcnpatiuns. The only exception to this qlJ.;l'rvati1m j, 1Jffen<i lw the ;i,h(,to'i" L.u1u:1:, ui the !1111g, 1rh1ch atkctcd in a ,;Prie.; <ii 32 ca,e.;-for which sex data arc aiailalik--37 rnaJe, and 15 i\'mal1.,. n:pn-,eating a m;ilc-fcrnale rati'J of ..?.;11 1!-:<'lI<Tal ratio .::..:1 ti> 10.1' l.1uai1zati1n ,,f <arr11Hi;!;lllr -..p<hllr<:, a,; rt'JJJ'<''t'!lt<'d h1 ;i,]",to,i.; f"r tlw t1\1i . 1:-.1-,. tlllb n,ulttd in a tr\'nd tu11ard l'<Jll,tit1'.;it1()!l oi li:tlnli1_1 to Jun~ ,;,m('r The"" 1Jli-tn.1ti"n' 1\ hid1 ca11 I w dt!J ,Jicatnl for "tlwr ',1rc1n"grn, ;,:id ll<'' ah" rlr. :;it J;l\-.ir tl1< C(l!Jl"t'pt ,,i a ,(., rl'lal<'d '-il""'I1tilJ1!it_1 t, l111J~ c:111n r. 2UO I I . l . JI l I 1'LI~ 7 ~ "' ,__, c: I .2 - ex: : ~ .,~ = ~" ~ - --: !... .t.,,~. ::;; ~::. tr, '-, x ..-: 7N ..,. c ~~'-' " :,.., -r'":' '-..! <".' ~;..;: 2 ...., ;: .lv.r,.;, = = tr; 'C .,~_ c .., ..,,.., - .:::..::: J ' t_S., ~ lr, u, lr, ...::; .~... ~ ..:...- ~ "'=::: ~ . . . g_ i:... . .;:; ....L i -J g - - ~ r ~ c lr, ~ t .2 "...' ~ c t ." "- ~ ~:: ~ ~ ~ ~ 'J, ~ ,.---"~ ~ f ~ ~ ;:: ~ ~ ~ ~ "...'. I < iI-"t' E ! .E - g_ E f-- ;..., 1;:; ~ ~ t- J. ~:tJ3 r. -~ I- :.., ;., -.;:; -: ::. = = "' ~-~ ~ ~ I _.I . _c.. - '_, ".,"".. t ~ ~ c' - :::: -~c g g~ R, ,..,,. "' <r, r--"---., ) ~~ ~ ~ r ~ ~ CJ, :.l I .':: "' J 1 ;: ...< .'.=: ;,..-; :, Of ' --= I '\ \ J HI I'\ \I ! '\ \ l ! l '\'I I \ '\ \ I~ 2(11 fll<ll '\\! .iJ"/111,'u 'JJ. I,' :11'! \ _\ ~1:.:: _\..;bt.::-iti)-.. Cill'1rn1:t!"' l 1lr1JlllC p1gll~t"J:', ... Ta1 iu1111._' ... I1 1ni1ing L1-dt tt1_11'.. l or 1tr1 Jl '! ,(],() .10 z -l .>1 -lil ""() ]> 11 13 -l] .~11 \,, 1,1, 21 2-1 '~ l q() '\'' '- lr1 ') .'-i ,,~ 11 I 711 \, . 1-l 31 21 ) -' till .'il ; 33 12 ~! (i 5 311 Zi 3,..:.: ,'.' ,,, l.t1 ]I) t)\} (J 222 12 -l-P 2..f f1' 'I! -~-l ~ ~ f J 21 ;1 ,\ ( h cr- \",, 1(,,t -1'1 qi) ](I 21 ! 13 f)2 3 17il2 Thr marked and grO\\ing- predu111i11a11cL' "i rnak-., an111n.~ lung c:im(r ,-ictin1s 'ce11io; largely to be due to the folk1\11ng fan"rs: L :.\I ales a re more extensi 1ely ernploytd t h:m i<111aks in ocn1p:it ion' \\'hen: k!l0\\'11 or suspected atmospheric carcinogen' are pr()d11ced and used. :md work more con-;istently and onr l1111ger 11eriod..; nf their Jin'-., in siwh occupations. 2_ :.\faks predominate in nittdo<Jr occupati<Jl1'. rspecially in urha11 area'. \\'here they become expri:,rcl to carcinoge:1ic poliutant~ containcd in the general atmosphere ( efflurnts of dome~tic and indn,!rial iurnaces. cxhanst of ga..;oJine and dirsel enginrs, du't from rul,i,er tire,.,, and a-.,plialted and oiled roads 1. 3. :.\J:ales more often than females perform heaYy phy-.,ic;,; lalvir reqwring- elf'<']' and frcr1ue11t res1Jirat<1ry lll<J\e11w11h facilitating tlw penetration of c;trci11oge11ic air pollutants i11tn the di,tal fJurtion-., rJi the re,piratory tract. and thcrrliy increasing the freqn<nc:- and degree uf exposure . -1- :\fa]e, 1110re often than females \\ <Jrk througl1 the entire ~pan of their <1cnqiational life \\'ithin 11rlian are;h \1-ith pn 1\en carrinogC'nic atJll<hJ,!Jeric pulh1tio11, \\'hile frn1al<..; t<> a .~rf'atc-r d(;.;r<'e than rnaJe,, ,tay ior hrger portirn,, of their Ji\'(-, in the clt-a11<T ..;11Jmrklll d"rrniton COJ 11111\l ll It)(',.;, f I istolo!fic Typr'S of Ococ patimur/ R <'S p1ralur_\' C.111,1'rs. . \!though t lw infon11atiHl ;l\ailable on the histol<Jgic type-. of <iccupational rP<;pir:itnr: ca11cn-, are qmte dl'l<'ct1ve. it i,.; apparent frnrn tlw data <111 l1and. :h:lt an11111g the n,piratory cancer-, recorded ;i, ,,f <H'<'ll)':tti<Jllal <1rig111. 1anou' hi--t11l11,gic t_\)>l'" occ11r. and th;1t tlwn drw, 11<1! <-,i-.,t :tn.\ rclat1011 lwt'.".<"<"ll a 'i'''citic <tirilog-ic iartor and th<' Jii-,t11l<>C'.ll' t_1 JW ,,j ,;in rn11111atr111- n'1'"11'<" 1'I.)1. Tli<' lltlllHTil:tl rda:1r11h i, t111n :Ji,. \':trr11h iihl.,]11c:w t:>l'"' 1I <>c,upati1111:il rt-.,p1rat<>r: ,;uw1r lrc1tl'd 1,., dilJ-, r' 111 111'.1111n nw11t:tl ,-:1rcin 1g'11' :tr(' pri-,t11tl'd 111 T:t111, \ \- ! r .. .!ll.! II t . 11 l I. I' I H Can111<i111.:" '"lll!h,nl ,,{ 't'\'tr;il hi,,tolP!.!il' t~pt, \\ere !'i'j>t':t1t"lh 1, sen-cd [:-djll:1n1"t1' c,ll-:\dcn l'a!li11on1a \\ irh ;1,.,lit,t<"i' : 11.+ : ,j, C :11hinatinn:, oi ,,.1u;unuu' cell :md ;"1111d c1ll c.trcl!lot11as 1 :-;drncclier;.; l";l"' l'Cr<; I ( 15 t I 1 T 11<1.F ::\.\ I! //11 1 1,1u1 /yj'.,_,. (if (Ji'llt{'u+.,,uul /\'11p1ri1t1ir_\' 1:n,,11 .-\~ent 'jar fume' :.. "ht'l Chrun1i11111 :\ 'h'"kh Had1mnivc gaq< anrl dti-t :\ ickcl l\adinac-tin: ga ..c, and dth t Isopropyl oil ( lr.rn r 1m.~ l.tllf: l .llll!' 1.un.c: J_ung \'are' a::d ntl...,al .. i:u..;; '\are< a:1tl :1a~a1 :-.~:1uo.;; :; arc< and 11a .. al '-i:1u' ~(j\l:..1I1Hll1;;:, 1..1..'l l l d.r"- i- :i..1na \11th 1r \\ 1tli<Jut ..> tri11 !l1..:atioT1 J 4 11 I 4 l\nund cell ,r uat cell rarc1r 11 '!11a 2 2 9 _\t1dpl.l....,tic or pul~ 11111qtl11( c;trr111t111a J 2 7 \ 1l t;( CdTl' ll" >, .l 2 Ii 3 -- (J 3 4 It may ]Jc mc:ntirmul that a multiiocal ongm oi ,-ariun,; ()cc111,ati<>;1;il respiratory cancers ( a~lwsto~. ionizing radiation 1 has been rqiorted li1 several investigators. This obser\'ation ma: lie interpreted a,; rdkcti!1gthe marked severity of occuriatinnal exposnrcs :,ince nmlticentric c;,n1n,genic devclopmu1ts are rather commonly oliserYed under the almCJrmal and extreme exposure conditions practiced in experimental can-inog-u1ic studies. Causal Jfcclw11is111s. Biochemical neactions of l~espiratory Can:in"gens. ~\part frorn the rather diffme cau,,al concepts such a-; heredity. cl'l! misplacement, and chrrmic irritation, there ha,e lwcn <ilitaii1cd <lnring recent year,, data on specific chemical interrcactions of re,11iratory carrinJgens \\'ith con-;tituents of the host organism. It ~eerns that all of thc<c reactions are common either to several or all of tl1e knmn1 n,piratiry carcinogen'i :md tlwrcf1 .re !l!:ty fnrni:,h a :;,iu itiliLall_1 "JllIJ<ttT iia ,1' 11 ,yinture imec.tigation" int<J the nature and difkrent pha:-.cs of the annal chemical local and ,,y~t<mic. hun1oral. cytopla,;rnic, and mll'kar change'"hich ultimatch tt'~tilt i11t" cancnou~ clltilar tran:-ior111at j, in'. ~ulih_1dr~. l lnarti1at1rJ11 !>tiring the J1a-,t t110 dcc;tclt,, \art<lll' lll\'(''t igat<ir.,- ha 1< 'ho11n that ~<1 <ral carci n1 ig('nic qi] "t a1 ll't'" :in 1:1" ,t 1 I. \ I J 1'1l \ \I I '. I \I. i '\ ' , , \ '\ ' I k ..'1 1,; ,uifh_,c!r:, I gr"l11l", a11d tli .. nliy L':J11,t :111 ::1ct.1 :c11 .. t1 ,i ,1:lih1 ,Jn I :lL'- ll\ ~ttcd t'Il/'.\ 111c" and di ... tur!;.ttH'c:-. in drt \ t ::~:' ..... 11. l;ll~, :i1c t~ . L .i1:--111 , ti; ,-.; !-. 1-~(J I. :u1d 1hat chemical cal'l'l!Hg<n, 1n:.\ ;-,,. :n:ict11-:ict'tl h L'tllllhinin'-'. 1Yitli or i11duurw ,..., "'idation of ,u]il11 dn l c::-l'l - 1 ,;,; '' ~i1ch C'tf,u- - c li:nc been dtmtiJhtrated for 'j.Jtt prudtll'l' -,r -..Ji111t 1[1~ ,,,11tn'1;1;:.,J,en/1 nr 1 ].)9) :1~ well as for ,)...J.-IJC'IL-'.Jl.' rt'Ill' '_::; . :\>: wv1,c lcmon<tr;1tcd 1,, JTuep('r 1~1 rrl 18.S i. f(1r i( 1 r:i.-::L~ ~-a1L.d~ii1 __ ,,. ,~ t;.111~1 lnr,i(~h.', gro\\t]1 promoting material ( cmlir: o t:\.tract 1 \r,<::1ic:-.'' :ire L:> i\\ 11 l<> cnmJ,in, with all(! ;iccnmulate in ti''ll<'' rich in ..:i;iil>\ ,1rd c;r i.1JF qiidenni- . hairs, 11ails ! . = There thus cxhts "' 1me 1:1idvncv th:tt l't'!'l:1171 1.~1 gt r:, ll.' ,;1ni111 igen- \1hich produce CtllC<T" uf the- rnpir:itory tract n.l;;J,it th nwtal1 ilic actic,r: of free s11lihydrd groups ::md 'or may ca11..:1 cn1::maric and oxidati,-e di'- turl1ances. The cxte11~1,e mdti,.,t;ial use r,i r;ickt; and chrurni11111 as cata- lysts. and the inhibiting action of lwryllium rn alk:dinc ph<'-phata..:1 provide c\-irlence s ugge,,trng other act inn nKc hat: ::-ms of ca 1ci nngen c; upon l'nzymatic acti\itit';,. There exi,r,;, more01-cr. the po,sihilit: that through a lircct chemical action these carcinogens ma_1 liri::~ abnut the production r1f abnormal endogtnous substances. such as ior in'itance <.tcroids by an 'ixidatin effect of chromates on cholesterol , 53 .. Protein Conjugatium. Follrnring thl'. ,uccc-,,iui arti~;cial C()njugati(Jn 1if aromatic chemicals and related c:arcin(Jgcn, \\ i:Ji r,rote:n" through azn-. "r i soc:-anate-. or ca1hamido-li nkages and the i f()(lucuor: oi carcinogen- hapten specific immune bodies in the serum of animals 111.J cctul with such ,ynthetic antigenic rnmplexcs ( 3-J.. .'.i-J.. XO. IO:?. l-t-J. 1. attempt< were mad to <lcmo1i;,trate similar hut ']KJ11ta11eou,]~- i<irn1'.-d carcinri:.;(n-pr<1t!'in corn- plexe:i in the ti:i,,l!C:i oi animals e:.;p<ht:d trJ c1rcin0gcn, Fic::-.tr ( :;J , ~uggcsted that carcillogenic puly cyclic hy<lrucar],rJth n1igl1t c<1mliine \\'itli cell protein, 11\ the opening oi an S ~ ltnka;..:-e. \\'hile the actual e~ i"knrc oi prot<:in carcinogen c<mil1inat11m.; l'.;t' r;r,t ..:]i.;\".ll in t,,nn~ctirin \1i1h lwpatoma producing- amin()azri dye' 1 1:?~. J:2(J r. :\filler (I :z_:; 1 ..1w- cceded al-,o in demonstrating tfw iCJrn1ati"n 11i ;1ri it('in lv,tm<l rlni1;1t1\c, ,,f .l..+-hcnl'.pyr('ne in the epiderlllal fra<"tilln oi rnothe ,J.;in ft j, lik<h that arscnicals combine \\-ith protein liCJund 'U1ih:, rlr:-l .:.;T<111p.;;, and therl'.li_\ form arsenic-prot<>in cnrnplexe~ \\ Jiich m:1>- :.;11 ,__ ri,< at :imt, tc1 ;dlu gi. nactio11'. The not i11ircqucnt l1Ccttrre11ce oi :t!kr:.;ic d<-rrnatrl'it;, in wurkcr- expo<ed 11J t\111 additional n,r1rat1Jr_\ nwtaJJi, c;1n1r1ri.~t11-. nanwJ_,. d1rr1- rni1rn1 and nwkcl. 't1g;.,!!'-h tlw i11n11atii1J 1i c,,rn,1irindJr-..~ ]>r()t1m criru- plt-xt:, thr1J11gh li11Lagt, "i tlH,, nwt:d- "" rtL tl:' r,1r!" \ . :-. lndrrJ-..:\]- 1,r ,uJln dr.'1-.:.;nill]"' <Jf tlH :1m111" ac1rl' Jn i~.-:t. n~c<rJt irnt .. !i~:il Jon;., I .rihC'lc1ir 1 10.'-' . a' <.1('ll a' I lti"J'n. r(1l1;,--.()Ti ;111<1 ( ;r(J,L!;\11 'I() I 11)] ' ' ..'.ll.t II 11 l I I'! R :trn111al' 111Jl'l'tl'd -.11tli 11rl1tci11 ....,(,Jt11ic1:., ~:,t\t: 1lll'.lili'<'' rt<i~ttd ui dirornn1111 and Jlll'k('l c'(llll]><>tl!ld" 1:1 L()lie:- . . \ttcllljl~ .it n1 1klll!l,Trati11g Lht pn1 1111..:ti11tl .;innlar- ;11 11i 111cral "']'(('iiic .tnti- 111;tt1 lll:llllltaC\l\' ,:-..:, :'('\'\,-al ,,1- \dl<.>!11 liad Jtiliodw' in tlw .-tn1111 oi dir"- lh\' lung. ga1c < :-.en-e ;;1",-al :1 ,u]:'. li<'Cll <Jj!l'Lll('>l <JI! i11r 1:1tlC('!' ,,i Ui th<' p(i,i1i1 pnci11nin react <l 111 tlie,e t\]iu-imc'!lh iri1alellt clirrn11i1:11 11 itli lrnman material. a11tige11' ion' ,,],_ prepared with 1d1n111iwn :1cnate 1 gan'. in general. m11re consi.-tellt :1r,ntldell'tt rnchnrug1e11r11r1e1a1c.-:10j11{,)lt.il'i-.'mitllltlh"c'hero,,mJiatatien)e.d 1_1\.i;r.h-uantig<11.; ,-.,ntai11i:1g lic:-.:t- :lll<l Uppcnhern1cr di~:;o!ved 11.? 1 .. n tr11alc11! and ciated .;1udie, lHxa1:1k1Jt cl1ri111iun1 of Grogan cn111p Ill lnu11:u1 pb,ma aud k:-.tul iur the pn,~ciwc of metal ou11d., protein tc'"l1e1c1trpokpxPh;o;rel,iyis. tha:e1dtcdli1gnh1t Jl,lC._:':a't1tfnmdigaly~i..,, moYing boundary. and paper dcnce supporting the phen"nH:na. i1111nunudiemical ol.1,enatiu prmided che1nical e\'i- }!entio11 also l k:\ardi ct may he made in thi-; ns. cnnnection of the ;,tatement oi al. 1 3/ 1 to the etfcct that the pulmonary granulomatous re- apcrtoiotenion; c.;occmnplienxeL-1edryiclilti1on.;;.i.':- a:rren aatltlreirlgmitcalirleeactt'>ionth. e Tfhoer~meation of l1eryl!i11111 ,,;en-ation:i on the formation of carbons and metZt:s po~:;es,ing prntein complexes by more recent 0!1- polycyclic hydro- dHe>mo-ailergic mutation carcinogenic theory proposed properties lend s11pport to the \1rtb the de1-clopme11t of bbdder cancers by Hueper ( 82) in dye workers in connection aromatic amines tJeta-na1,hth_llanm1e1 Lenzidine ( 121 I exposed to certain Recent studies <Ji and intriguing Eng Ii ,;!1 imestigator~ ( (>5, 70). J. ha1e furnished a ne\\' cvncept as to t1.;suc proteins thr1.1ugh the po possible combinations of carcinogens with carcinogenic chem1cab and thsteulmateadcroiomrlollleation of cross linkages between This hypothesis was ernlved from cular tihers evidence obtained of chromosomes. carcinogenesis hy nitrogen related compound~. lllthtards, <li-epnxides, in the study of polyethylencimines, and which thC'~e In vie\\' of the fact that one of sub,,tances may exert their ~pccific the various means by through might polymeriz;ttion. it is as-;mncd that action polymerized in the cells epoxide is cross intcrreact \'. ith linkage with protein,, (Jr nudeoproteins of d1ron1o>omal chains origin, by multrp<Jint attachment, and thereby cau:-.e mitotic aberra- tions. The initial naction 1~10lecules 1 with the cell c of one of the epoxide groups of monomeric tinn by being- f<,!1.-,,1 td omponent abo may lJ_1 a seii-cnndc start a prm'css <1f polynwri7:1- nsation of the free into a polyethen()xy .'>tructure. epoxide group' The,,e n-a-,011,. conncpt-, They arc (Jf intcrc.~t to rc,,piratory carcim >gene,;is ior scnr;t! 111:1y han: direct applicaticm to the dc\clopmcnt nf pul- n1"nan ra.1Ker, :n c1>111wcti in 11 nh occu1,ational C':-;po,l!n-, to ,ilir1J11 J .\ \ [ j~( I.\ \ ! J .\, 'J \ f. f. [ "\', 1,_ \ ', l ! '"'.'. __'11_:; :1rili carl1(1ll JHil\11Hr-... 11a111l'l_,. :t"'l1e:--t{1-.. :u,l l"'"l1_1lcnt, a11 i-..1 1 J)~,11J_\l 1'l 1\:<i! 1t.:n11n.!...'. JH)1\- il "r 1.-o!'n1p_1l ('l'"'-i<J<-.-; 1-H ..--.:1 .. ~!Ih'< n h:1, l.,,11 ,lH11n <''-J><'rillll'!li:dl:- tliat :ti lc;1,t 11;Jt q1ll;.,:idc ' j -:; .~ l 1Tlng(11ic t ;-1 I, :lH (1iJ .... (_'f\":lt~11TJ:--:. c1i 1'-Ptii~ ,~~ -;-,]1q'"'-1 lnlt;11h j, c;l!'- 11rt>t'm'e ,,i <'t cutin"gcnJC u11,atur:ited :tlipli;1tic ,;,; tJ~, 'l'"'i1:,., i1~ Los .\ngeh, g-ain i11crta,td in11,onancc ;,, '" tl 1 Ct,tlCtTlllTlg- rl1c tl1v at111"'Jlhu1 !i:ttllJ'( "f l"'"jl.J, carcinng<flit' :1ir l'()ll1tt:1uh i11 tll kmizcd :1n:1' .\dditinna! potential Ill relation to pulin l''\ kll.-li n.; ni ere"' li11;,i1 :,_; c1rci1: '.'-'. t111c J>1Jl_111H r' nwdicinal on:iry c;1n1nog-enc,_.i, u.;e of pol:>1in:>l :ik< ,Ji,JJ a 11:1_1 :,,lilt fr, ''ll the 11nlpt1-t ,J n.traperi1>,teal plomliage of the nd plellra: 11wtlil'lnl 1};;,_-r_1 hte ca\ it\ f, ha]], for tLt collapse ti1 of the lung lwcan'e ui 111ilmonar_\- r i1t-11nng udc-rc<1l1,_j, ':--:3, a pn111arn111 1:--:<1 Jn may also he made oi the fact that t ''" 12 ''.'ie rnol l c1ila r 1. }fenl'"l ' n1c1-,. 11:m1dy. J1<il_n inyl p_nrulirlonc tniduced a~ pla~ma and dcxtran. -.1 lii 0J1 han rc-ct11tl_1 been in- C\.lt>l!<ler,.., are Ill ]>art arre-ted in the plllmonar: ca]'illaries and enter the capillary endothelial y;hctilar ti~rne. therC'hy tun:s. Th<.;e medicinal creating- intimate: lining ;rnd i11ter,tit1;il c<>11t~1ct 11ith ]'ulm pcri- use-' oi ,arious natural ;,nd <1nar:- ~truc ,;ymheti( polynwr:; eafrfcecotsi p(o-Htu.iti1a3l5,sig1n9i0fi;canpcrre1dbuecat1'c oi the dernrin,tration of caninogcnic jcritr111cal and sul,cutaneous ced in n1ice and :-ab irnplantatinn oi a f"])1,1\i11~ ;in int1-a- dwmicall; closely related pol; mer.". "llch p<1ly1inyl chloride. :\ylon. acr_:- lie n,in. c1111-i<kr;,J1lt m1111lwr ,,f ;i, c1.-ll<j1ham-. l"'ly(tl1_dc-nt-. I" 1!; a1111de ' E-c:qmil;1Cta111,. Teflon, and :-.;j]a,tic. 11hether or n .\lth<Jug-h there are JJ!i ,,Jhenati(Jn.; indic;lting ot tlwsc tirnli11g,, i11 ;rnimal" ma_1 ;q 1j ,Jy '" m:m. it appl'ar-~ tc he ll'i~e t<J keep all imlu,tri;il 111,rkn.... wh<, \1ith tion funw.;, vapor-,, an<l and proce~::-i11g- dust oi tlW'>C' and llla: rclat('d kl\ e re.,;iira1,,1-.1 Cllllt:,n J><ilynwr' in the produc- of synthetic pla;,tic,; and te:,tilc tll>cr.;, :m<kr r!<J,c Tlllh<e'd,,iecapl re;c.uaruntiiolnla-n; caerefuarl,oa inpdoi,c,saitl>eldc ldwCc'\aeulo']c'11 wn t of re:-I,j :at< in c;mc<'r., sthp<'ctl'd cata cl1ernical carcinug<n~ (nickel ,,j t!'1 n'e oi "'111< kno1111 rir carl"1n:- l. arrm1atic ly,t;, and 'or )'ol_rlllcrs meth antinxidant-; <n- curing- agell!" in the amine' 1 a' m:urnfrict11n ()f th('-<: I acr_1 late plastic'. synthetic nil1l,cr: t'J"'"' rc-~in-; 1. ,,u11B1aelcafurasgem1_e,f1Jthtaetio,inmialnadritylmo<flgt"hei1 cry!1t1o:l1oti1g,inc alter::ticiri-. <''['t-ci:dly chrcn111 ,_ \ariutb ali1,hatic carcinugen~ 'twlwd hy ,,r ;u1;qih;i,e. l l\ndr_1 , I r1/. r j,rr,dunrl In- th(' d"11 U1;i 1 to tl1""t ..Jicit('(I li_1 c.tlkd "radi" i"11i/ing- r:1,li:,1i1,:,_ /(J. /I, and I f.ulthir :.l ;i1n1 h:<- 111111wtic." l t ii"nizi11g radia:1/J1l 111ay ,111 1nl<'rt'ti11g- t." !i(Jl! in thh ))('I'll .-1,11rwct1"11 1!1,,: 111cr' ;;.., \\rll ;i- ilH' i1Jri111rantbi"trc. >lq"il_1nwri/;li:1.i1 ,,j 11;acrr,n11il1-,1il;;1- 1111l:.- cli:1111' \\.lwtlwr ,11cJ1 \l(<lh ,ir1<ii:-1,etir1"l' "Ill11t1l,:,;.,,,'-;'.,~.,,,,:lr: 1tt"i.r.-1Il 1i}"11!_11il1111!111-'.1i1<,:,:;1. .. _!()( I \\ 111 I I'! I( and 11a,al -ii:1, L':tlletT~ in 1111fkl'r' ('.'-P"~cd !<1 rad1oact11(' r 111'\\C\cr. ~ ... ;,I,l1..11L11i\c 1 i;q \' lthl :Ille! g:t",'' The 1:1ri 111, 1"h:-er1ation-' 1"1,..,ililc li1"'li1:~11c'a! and ln purl1oe' di,.,,11,,..t'd in nlt 1011 to tlw cinoge11C'-i' Sl\C.:~t:r ch:111gv' underlying lint .-d! agents seem emirt>lllll<:lll:tl n,piratory car- 11ith protein' 1or nuclen1.rc1tcins and to interact hy -0111t mechani,111 prociuce. thereby, ;ilmorm hToh1e1es1ilgT1.lltri'caumnd l'r!1tf'rnth1ei-r<n:dr:rntt>inic alteration' to ilw cancerizat iar1ln pprortoecine-';';. Specific Respiratory Carcinogens and CanceI"s The rc-rir;.;, r'.' carcinng111' chclJlical :md 1h~ ~1cal ,,., far ncog-11iztr! differ gTe:Hly 111 their ill \\'hich tlw_1 comt> l'ropertic,.; in cuntact a~ 11ell as \1ith the in the phrsicocl1C'111ical .,tat11' clwmical agent:', :'uch as ,-ariou,- metals re,piratory tis,ue. or metal compom1d Some ar<' chrorni11rn. nickel : . or minerals oil), or ar11111atic ( ashe-;tos 1. <Jr ;J.]iphatic s (arsenic. iJr;~anic ( i~opropyl pitch, soot. organic cnmponnd'i ( cliernical petn;leum dcri\a[i\es 1. Other~ carcinogens in coal tar. t11rnugh Jihysical forces i ionizing; exert a carcinqgcnic radiation;, such as the Yario effect actiYe chemical.::. They ftimes. mi;;i-. ,apnc~. fcnter the respiratory tract in the us radiofnrm of duq. anrl ga!'es. lJt>pending upon the particle "ize of the dthiespreersspediractaorrcyinrt1ragcetn.1cIfmtahteerpiaalrtitchleeys amrcayraptehnlrdrlaartege,intthoeydiffcnnt parts of ocathnecrerhsanind.the li)'l'er part'i 1 misil c;n-ity, larynx) prodncc main!: They ma;. enter, rm th<' sinuses, if th<'. deq1er IY 1rtions, they are nf yery .::m such as the brrmchi and lung or parana .::al gases. all particle size or take the form "f Yapors fir ~lETALs. Xickel. metals, and prin Xickel, one of the most indmtnally imprJrtant cir,ally mined in the Sudbury district of Ontario, Canada, afinndds mmoalynbydeunseusm (.1.alelmoyple<dJ_nwrilthinirothne, cmopapneurf.accthnrroemium, alumimun. cobalt. resisting rods, ... tcels. forging.;, ca-.ts, wire:;, sheets. of stainless -.tetL heat structural sha1ws. t11h bar<.... trip,;, etc. 1. electroplating, colors, pigments in paint~ cataly~ts. ceramic cnanwl-; i11g. and Exposure to nickd and ink-.. storage batteries. fume-; and nickel dust etc. c<'1mpnm](J.; or to nickd carbonyl of metallic nickel and Yapors is. therefore, freqnent for ib tfial \HJrkcr ... of many types and in main- r,f)('ration~. iwlt1..;- ThL Ji1 ...t rel'1,rt concernmg cancers of the na..;a.! the occurn"rKe of an exce~~i\'(' nmnlH'r ni pa-;sages 1na,.,al caYity and parana,;tl ..;in uses) and u\fictkheel Cltommgp, aanmy<]m(J~ca\tu\(lJrakter:--;:;o<uJtllh t\h\r'aleC~l.yrElandg1lapnlda.nt\\'aosf m1haedeIn1t,y1: mat ion a) 1 (il) in E.132-, althrJ11gh tlw tirst ap]1f'arance of the:,e ncoph,111, <;nnfcll ;un"ng thr .\ \' J ti II \ \ l l \ I \I. I '- ; \' l f' _!I I. 1i11r,1~(\.('l nllti'l~tuT\ \\Prkt:rs \\a ... n1iti1.:cd in j<1_2-l 1 ~ .11 ht'1 J: l'~:' , 1e! 1r~" !c:t l -,1, d1L .. c cauc~ r.~ \\ t'rt' 111:ldt- 1)\ '_;_: ( 'ar: 1:u1 1_'.<I1. and \ftrc11 :-: t t'\ I "l' I 11,:? I H _\1111 ~- \-+' C\)tl})('l \1 her l ..?.+ chtIt' \\t:ll' lll1til!cd 111th the I 'hwi !11-JWcto: :-~:-un: ,; :c1_?.~ ~() ~''-t~ P'1..~L1:.-...J\1 1i c:111uT "i tlw 110:if' :rnd ~.? caS\''- "j ca1K1r F:h t11ril,; ,\ ,.1:.i! ,-,i the hn:.c: :,., "i .+;- "'''" 11,.rk.; 1\y the h1d rl1Lr! end 11f J<l-t,'\. -ki "i tlic n:,,J ,-:mct'r :'tnd lll t!ic 111,k, 1 :- ..? "i il1" 11111 t',1-..1 ... Jia,J C>JJl!IJt'!lCed .\',qu. oi tht n:t ....al 110rk in the nickel i..'a"'l'-, ;.::il 1 111iy l\Yt1 ~)f tht~ Jnng C<l...,(', ti"n .ii tilt plant had lwcn carried rc1incr_1 nut ,,irt-r 12.+. 11 hcr 1 .1 nc,)11,tr11c" rllc 1l1t ...al cancer .. \\a:-; 23 year;; TJ-..- .il<'fag, c"'i"'"'.lrl' p1n<1r] ! range . .~~.!n _\-( ar-.. ' i"r 1:;tt11.."t'r:-:: 2.~ _\c~ar.-.1 kt1<' ocntrretl trange. 1-3J :'-~car'-'r. :ir111 inr the I11n!..'. :\ . 1 .._'"~, .... '- .... ,,f (ar:c<.:r 111- tht 1ar,n, Cini:tcl1. . :rnd only one c:mcer oi tl11 :::1,11!;:.ryll.'. 11:1-" nli-;er\'(<l at The na,;tl cancers ,inn'<"' 1ctlirnoids). iinoh-ed Oi the turlJinate-. ;a-a) 'l'\>l':lll. and parana<il ccll c\pe (~ix 1 :;omc the.;;e the n1ajont:: showed a ~quamou~ 11ere oi thl m1rlifft-r111tiatcd cnl111m1:1r cell carcinomas were 1mcom111nn cell character 1Three 1. 1(1!Je '1 ()f the lun '' l!il<' .,[ 1 liid1 Jii,tolngic ' ,f t lie ~n 1:tll cell. studies \1ere :n-ai!ai>le ;n r:inly i11ur ca-c-, g cancer.;. tll!'ee wer,- J]I 'J)] Lt. pleCJ11101 phic 1ypt>, 11 bile nrw was a squamnn.; ct>ll carci- ,<, -;1milar ol1,cnation~ rt!intn-. 1:liere three \\'ere ri:cently r('cnr-kd frrn11 a ::\nn-.eg1an nickel tht"~ 1 ,a,n a ca,;es ni lung- cannr ~qoamous cell carcinoma 11('rf' <..ecn 1 ]()'), !11 "ll<' r1i l ;,,]<]IJbtt and \\'agstaff I(,{)) 11as ;1"rciated with 'arcc,irl lc-i1 J)lS 111enti1!lled that rc,jJJrat(Jry tracr tlic l1tTn1~u1 ha1e not he(n nitcrl a11ir1:1:; the far cancers of the \\'l1rkr- (rnplr1:dd ;n ;l!l lllll!,l!al nickd refinery at T.wh11g-h;tiu,, frequency oi re.;p n,r h;,, there L('l'Jl 11]1,tn(d :-:.udl 1\1n niche] ure rni1ws iratory cancc,-,; amnng and ~melter~ in Cana thr \11rker.; "f th1 .\11:"r C ( .j. 1 pointed out that the niaj11rit_\ da ni inrli11dnal< e111plr1 l11i.ili. 1\i10 dc1clopnl n.;1irat<Jr_1 CtlKr;,, inli:dat1"11 r,i nickel ynl at \t'f(' nt e.'.j">"l'il tn tlw ir11p; ihe niche] carl1on:l. but matte roa~tcr ( to that 1.i ;.icktl rnatt1 rJti,t. 11r i11ht 11: \l11rgan 112/ 1 cunfirn1c.J thi.; ](J'.) 1 . .\J1,ri rtTent data fJlhenati<Jn. ,1Jtl1(Ju~h t'r1r1111!l1111c1krl ':1r!11ir1.\l 1ap(Jrs tl1;,!1 ;q11'are had occurred more inr11wntl:. amung '"'-l'c,,1.1n'. T<J nickel th(' affected \\'orkrr, l11~li nt iri,111 tlw d:1t:t :!"":i1Ju~ly 1midei1ce ui c;u1nT of t!w na~a) g11(n by _\m!Jr. The relatinh ,-..;u,,. p;1rtil'11ble j ilth( n:1.!il1 :irr1,lc<:1'd11t:1::'.. r:1n:d11"l. 'llgg1,b that a ratli<T llia.1 l::11T lw<n ,..J1Ji1 11ick ani1< i11 tlw - pn,<11wtil!11 "i 1 l'l'"'')!J ~ r,i '.t:-1c1:r, :1t tl11- :'.1 l!JJ'liin:dr ]''r1w1ilar -ill. 1l c'lllll:llJJJIJg 1;q1"r' <>r :1 11r:. 'J'::ill )':Ill! 1d:tt1 ,iJi-1 11111,J lii\c;\ .ttl't)lJnt lt1r t!i<' (auc1r, c1i the l11n,~ ,p ::i-<d --Jlltl--t" \..., 'f1 tJ11 1...111-..;lti\t' ;1:...!_<111. \;tr:1111-... tl111Jr1 1 ~ ~ c ~11't11 1]\,,r11(1l \"ii"'. .!O:-: \\ Ill l.l'l.ft fan,nd the Cl'tllTJH th.it the i11halatH>11 (lf 111i:--t fr,,11\ ar,,111C C<>llL1i11111~ ,ulfuric acid u,cd Ill tilt' reli11ill;:! 11rocts:-. \\'as the acl11e carc111"gc11ic :t~cllt It i.; 1110-;t unltkek tkn this j, C 1rrect becau,.:e the liickd rl'iimT1 11-..rkn' dl not :-.11ffcr irum jerior;ttll :1:1,.:al .'epta. and ,:],pb1 no nidt11c1 oi ch runic ar,.:enici:'rn. 'ud1 a, dcrrnatosi~ and cutancou:-- catKtT". \\ hid1 allllost al\\'a_I':-- h;ne acc<,lll]>:Jnitd the occm-re1Ke of lung cancer among 11urkt r" expo,ed to ar,t'nical <tll:--ts or fumes. -\rn"r (--1 I ,\:1ted that the rdined nickel-copper <)rt art frC't' ir"n: radioactive matter. The n:--11iratnry cancer~ uh,ened am(l11g nid;el re!intT\' workers 11111:-- :tre nut idt'ntical in etiology with those seen in miner,.: c111plu_1 ed in tht: radioacti1e mint, of Sdmecherg and Joachi111-:thal. \\'orkt."r~ en11.loytd ;tt the n,a.;ttT:'. in the nickel carhun:ll operation and at other pan,. (1i th(' plant. "n the other hand. heconw expthecl tu the 111halatio11 of dmt. fumes. or Yapors containing nickel. ::\ickel is thl' cnn1111nn ciennmin;-itnr inr all ni them. ft thus i.; 1110,.t prohallle that tl1e re-;piratory carcinomas ohstn-ed among nickel refinery workers are reaction products to more or less :11wly di,.:persed nickel particks or \apnr'. There is no e\-itlence al'ailahle. howeYer. 1.-hich indicates that the inhalation of nickel in particulate fir yaporized iorm i:-; accompanied 11: pullllnnary changes ()f a pneu111ucu11i11tic nature. The concept 11f a nickel etiok,gy of respiratory cancer~ was te-ted in a!limals hy Ca111rlJell t .:?81. who exposed mice to the inhalation of pm1dered nickel matte, and ohser\'eri that these animals had a lung tlltnlr incidence significantly higher than that of the unexposed control mice_ The recent experillltnt' of Hueper t 85 _l seem to demonstrate more conclu,,i1ely the carCl!l(Jgenic proptTtie, of metallic nickel. \\'hen purt 111(\allic nickel powder 11a~ implanted into the femoral and pleural cffitie' :mrl in the suhcutaneous tis;;ue of rats. cancers cle\elopecl at the site oi injection within 6 to 2+ mCJnths in alJout 40'/r of the 'iurl'il'ing rats. _,\rnong- 49 tumors thus produced among a total of 175 rats. 4~ were -;an'f11nas. and 1 was a ~quamous cell carcinrm1a (Figs. 3. 4 I. \\'hether or not nickel a!',"l1mt' a carcinogenic role for cancer~ of nther organs and following exposures Ly other route,, i:;; unkno\\'n. ft ma~; lie mentioned, ho we Hr, that Araki and :.1 ure ( 5 , demonstrated hy speer ro~raphic methods. nickel in human and animal cancer-; of various typ<'~ and -,.,it<'~. The nickd content rangtd from I> 273 111g, kg. 11i fre,Ji 11n11 1r tis'iue to 0.2 mg-. kg. ::\o assessment of the degree oi 11ccnpational nickel ca11ccr ha1:inl "an Jw made from the data a1;ulabl!-. 'in"<' tlw numlwr of 11orker-, at ri-h. i, m1kmnn1_ Likewi-,e. no 1k1inite op1nto11 can lw e_,pn-,,1d a-, to tlte i"'"il1l1 <':-.i,,tence and t:-.tt-nt 11i n,.pirat1r_1 cmnr li;var<J, ior jl(T-'t111~ h;ni11~ i"1- 1 '\ \ ! 1~ 1 i .'\ \' 1 '\ 1 \ J 1 r ' ' , , \ '. i ! H ,!(11 1 F11, 3. ()::-iteogenic .:;arco111a in tl1C" thiish 1)f a r;;1.t 111je\ ttd \I.1th P">'>\-dt:red nntallic 11ckel int0 tlw iem .. ral \ ein. Fir, -'" .:d yqb]a,f1c .. ;if1_'(l1Ud. iP the tl11)..!.h of a r.1r iil)n ti d intr J tht iln11,ral ( avity ,, nh n'~'-\d1nd n11t;.iJJli n,1~1') j';., ~ J\qUJlrl \l'll l'ir~i111HIJ;t (Jf the lt111g lll ,J. 'JfqJJl.if( F1<. IJ ,\f;i .. ..,l\L' depo-.,1t1im ,,j d1rq!l:Jtt' 1rt: '.:;-.t J'l ;1';t/1llLh't\HtI :!l.ilJ 1 lid.< t:JrtJ ;, ~ ,; ,L , ! JI t 1lllate ..'.I() \\ t.. ! J t Ll 'I.I~ other rl';h"ll" r<1111art 1\ 1:h du-t. f1u11c,. and 1apr:-- 1Y11lt.11111."' nick( I 1: ;, c'llllj><J\1!1(h. Chrornirn1l. Chn11niu1n as a llll'Utl. allo1. or r<11111111un.\ 1:-- ll'-t'<l 1"1 11lan_1 ]>l!l'Jl('"e' in indu..;try. !1 is ior thi~ rl';h<!ll that a brge nu1nlwr ;mi \aricty (>f 11 <1rke1 h:t\ c r"\lLtct 11 ith rhromiun1 and chru111i11 111 r lll- JH>11llth, and that n(!l r1-,tnrtL'<l gnn1p~ of the gc1wral pnpuhtin11 :11;c.1 l'"''il1h lwcrn1w t''.pr,-,,.,j '" y]i,.,,. ;1g('Jl1' in the fnn11 nf .J11.._t. y;1p"r f11n1,.,, 1111,..t. liqllld. and ,..olid I ..'.l 1. \Yorker" lll<l't likel:; to h1 expoc,ed to tlir"miu111 and 11' comp"unrJ..; an acetylene \I "rkC'r .... anil1n1 11orker~. l>kach-r-. Jilueprinter~. dirome \Hir;,er:-. chrrnrnwn platt'rs. Lhrumatt' manufacturer-. d1rrn11itc miner:', rra_nn maker,., <lye 11orkcrs. elcrtr"phter.... l'twnwl \1 orkers. gla~s and pnttcry fn,-ter.;, glass colon,r,.., j)(tten gla/.er.;, arti 1icial tluwer maker,-, battery makers. linoleum worke1,-, paint makers. ink makers. painter:>. photograph:c ,,urker,, photoengr;l\er;o,. poJi,Jiers, printt'r~. nil il>cr \\'orkers. steel \\'or;_crs. tanner_,- \1orker". n1kanizer,.,, waterprofrr, ui te..;tiles and paper. ,,elders. users of chromate anti rust agents I ]r,cornutin~ attcndanb and engineer~ 1. bitumen and oil n:liner_I' 1nlrkcr.'. i ,;;, ,tic manufacturer,.., n~getai11e uil pruce~ser,. Th..: o!Jsenatiun of apparently occupation c<,1mected cancer-,; of the rt'<- pirat(Jry organs, e,-pecialiy the lung. has lieen limited Sfl for to t\\'n t_1 Ji(.; of r,pcration.;, the production of chrornates from chrr.mite ore and tlw manufacture of certain chnm1ium pignwnt~ (zinc chromate. l1ari;u11 chr(Jtllate. lead cl1rnmate '. 111 th(''l' ''J>erations 1Jrith \1ater :--olulJ!e ;rn,J inv1lublc chromium c01n11r1mHb arc inhaled liy the exprhed 11orkC1,... The chemical nature of the actual carcinogenic agt'nt \\'hich 1s respon~ilile f,-,r the e:--ce",i\'e lial1ility of chrrnnate and d1nm1ium culor 11orkcr' to cannr oi the lung is still C(,ntn,,ersial. .\]though all i111estigator, lielieYe tk1t ~0111< chromiu111 cump11und ur ccimponrHb are cansally in\'(ihed. it ha, relllainecl uncertain whether rhe C(Jmponnds ~u~pccterl arc hexavaler;r or tri,:iknt. \\'atcr ~oluble <Jr in~11lulile. n11m1JChro111att' or dichrr1111ath. \\.atcr ~oluhlc chni111ium cu111pmnd., ( n1rmr>ehnm1atc:,. drd1nm1att. and 1.inc chromate I are nw>t Jitl'n incnminated. ::\fancuc,o ;rnd l!neper 11]<i1 recu1tly pointed out that ll may l"' more likily that cat'<..'tll"g"nic tffect' ;ff( elicited liy chrrnnium uirnpourr<l-. 11hid1 ;1r\' either 111Jt ,..,1l111Jk in '.1;1t1r or unly ,Jighth ~(,, lwc11hc ~uch chemical, 11he11 inhaled a'i dust ll'<mld -}~: retallled ancl dep(J:-,ited rn the Jun~ and thu-, l'Xt'rl a prnlo11ged 1fint np<Jn the puhmmary ti--1:e-. :-;uch chrrm1i1Hn uitllJH>llwb ]'rt'"('nt in a dJTwnatc plant \\'(J\lld l>c n-pr('S('lJHd li_1 cliro1rnt1 on ;md it' ;1rh ,., ll- 1rr ...irm 1,roduch precedi:g the forr11a1ir111 1Ji !lJ()n< whrr irn;ll"' 1 Jit.,,. little \\'atl'r ~olulilc tri1a]"nt dHr!ll1i11111 n1m1)(1\111.J-, (1cc1:r lll tlw 111au r1:d l1n,e1ll in 1111xer,, awl roa,ter-. and are c<ntaincd in the- 'b,;:..: 11 hi('li 1;-:1:111_1 i' :,tnr<'d i"r iutun u-e in tlif' :-ard an;, r,i th" ph11i... I."- I 11'0 '- \I l ."- I I I > I "-I. 1 \ "- l I I! ..!1: It 1, dt'ii11itcl_1 '1rr1in,i11.~ that ll "'l.<'"11<' li:i1>11it1 t ~1 ll:....'. 1,.":L lh.'t r lJ .. 1h.T11 c-.,t:thJi ... hccl ""() far ,inh f1)r \h111n1.dt \'.(J!ktr_..., 1il \ ;,_ -i~i:lll\ .1111i :1,l l'nited :-;tare, 111. 3<1. <l_!, llli, ]]<1., :t11d in dm"1l<': :..:nllilt l'."rk1--, in (;en11am (q. ](I, t1.'l. Hl-l. 130 i:id-trujl 1 )<i. f,,1111 , ''n:..:lt- ";''" ..; lung crnn-r tt)H>JJ '-ra_1 1,ami11,1t11111 1 1f th(' rh\''-t "f ,'lll ,Jini111;ttc 111:1rn:- i:1cturLT.; l'111plmed for lll<Jrl' than 10 :ta:.- in h1gl1-h jiai::.; 11]1il" 11" d.;c:, 1\.i ..... t 1111 thi .. pflint ln ri..~anl t() 1..hru11;1tc pn)d1Hi11~ 11r '-- 1 ..... \:;.1111.~ 1ilanL-.. in othtT conntri"' ... uch ;1.; ~l\'lli'<'rbnd. Italy. and 1:r:t1Kt .\part ir0111 tlw ,,n"1\t' irl''Jlll'll11 "i lung c:1ncl'r" ."lll:_: lh1-.n11:,t1 ll'(Jrk!-r,.. 11hch acc,,rdin.~ tu . \!llericm nlh1-r1atiu11" r:in.::.:1 in Ill 13 ---31 ti1nes the normal. :tll <llTUjlati"11al "rigi11 "i thl'"e r;P1c"r' i... _,tn!llgh -ugge-.tC'd Ly the .,Jiiit "' tlil' age di,..1nliuti<1n trl\\ard -'''tl!:~r agt' .:..:r"ll]"' Thi:- i ... particularly striking for thC' lung cmnr, prc,tnt :11111 ng Cnm;ll; chronic pig111ent \1orkers. -.irn:e ,=;or~ oi the cannr, afft-c't,rl irHli\idua:, i>dore the age oi .+O .'ear,- \\'hen lung canc1rs "j trn kn'"" n (\ iolo:.,:_1 :tr< rdat1n:ly infrequent. \\"ith the !'XCcption oi t\HJ Case:, f One Cat1Cl'r of the 11;,:t' I ] ,)3 i ; "lit: cancer of the maxillary ,.,inus ( 601]. the lung "1a, tl1e c '.du-in ... ite '; rc,,pi1at1Jry cancer,, olhern:d arnong chromate ll'orker;;. T:-." t( ital nu111lwr rii the:,( cancers j, at pre:ient anmnd I.+() ra!'>es from all ''>llrce.;. :\11n has lieen reported a.; originating from nasal ,..q>tun1 uln-r- Fi:..:. _;, Chnnniltlll pne\ltllfJe(JlJj(J~i~ S('('!JlS tri at'C1!mp;1ny th(' r'.(\'(l11pll1"ilt 1) cancer "f the lung in chromate and d1r(111w pigrnent m;,:rniactunr... It h uncertam. ho11e,er. 1d1ether the pnewnocrJniritir )'la-'' a 11 c ,,en' ial , i1 111odii_1 ing role in thf ;-,pccilic canceri/.ation proce-..; (Jr \\ h:-: 1wr it i., 11wn-k a phe11"111UJ1Jll oi n1inc1drntal c<w_,i-.tt-tK(' (Fig. ()" \\'hilt the attc111ph ()f Cro-.:i a11rl i..:rJl!-ch Ui31. and C:1:.q1lw!l 1..'..'-' 1 1" produn h1t1g- caIJcer rn rnice liy their ("\l""'ure to chr<imatt- d1i-,t \\'(')"(' ll"... t1CC<"i'Jul. ~thinz 1 l.'\31 and \"i1In1an11 (1771. ll'h11 in1pl;,'1kd JH1,1d<nr] <"!Jr(Jllliw11 rnetal 111t1 dw fr1n11r,ti c11it1 "f r;tlil1it-.. li-('l'\rrl. ait('r 1111r than J _l'('ar.... u111 a11irnal \\'ith ca11,.l'r "i the 1t111:,:: ;11ul ''ll' \\ itl1 t :tnn r ',; the fenl\1!' In a ... u-i<', ,,f pil"t t''-:)'( ri11w11h rTc1ntl_1 ('(') l\lct('d, :_:\1111"" pigs, rah and micl' \I('!"( <''-}Jl!,..l'd t<J the i11li:dati1111 r1i hr111ite r1rr d11,1 at a crJncc11trati"n 11i 15.;1,'litc-r of air i()r .~ ..(j h()ur.; dal'. ~ da\.; 11n" 1:. ior a t(Jtal nf ]!-( !JHJlltli~ . .) of th1 11 \\i ... tar r:1h ... hr11nd 11:11r1r- ill11.l1i '.: r<'']'iratr,ry urga1i.;. I lt1l' rat had a "illalllilh cdl C1!'<'lt-, 111.J 1 [-1;..'. 11rig111atln,;:..: in t!w ]'ar;n111'al '1t111 ..i, ;tllri i1n:idrn::_r 1:11d 1,j,,, 1it1t<~ 1J .. 1-_1<hall, 11111 ;1dd1ti1!ll:d rah ,Jio11"1l. at a:Itr'l"\, -.in11:,,;1!1., :.:rn\tli- 1-, \<Jl\ing th(' nwrlia-ti1;:il 1_11r11l1 r111<i' ;1nrl 11111;:..:... 'I !11 :"< ::,11, I J,J;.,' pi~111c11t \1itliir1 tlw tl11,k,.11,.,] 111t1 ,tit1:ti 11"111 '1111' 1:1 '-'.' : 1J.r," ~11'11 fllg'i rt\t;d 1<l 1>Tl h1--11,]1i.~ic 1\:ll111n;llJr1ll t :ii:tJL(,) ~11J1" r:1!J1dJ .ir 1,j1, _! J .! \\ Ill I l'lJ( hrurn:hiolar cpi1h"liu111 \1h1ch <>it,,11 uccl11dnl thc lmnchinbr l11111ina li\ the formation oi ct'!luhr plug:: co11;;i:--ti11g ni mal and ;;pindlc -;haped. hyperchrn111atic epithelial cell;;. Tlw-;e cellular ma-;-;e,; extended in place" 11llo the adjacent ;d\'eohr lumeI':' forming polvp,;, coating;; nr -.olid ca'it-. These changes \1en \1idely cli;;tn ln1ted in the lung;; 11 hich -.h<m ed. more01er, a ,;cattering of dark l)ri ,.,, n t() black amorphlm,; pigment located e-;1wciall: in the :-uhpk11ral zone. ;md \\'ithin ,\ tibrou' a11<1 thickened inter'itlti:d tiS~lll' (Fig. ;:: ' ..\r,;enic. .\r,;enil.1:, nprt,..ln; a h:-product. or \1a,,tt' prodn<:t ui tht ,..melting of many (fff'' (copper. zinc, ;;iln'r, cobalt. anti111nny. iron. lii'i111uth, nickel, tin, and lead. :\r;;enical;; are present in the -;melter fume, and slag heaps. They are exte11-.1 \'el:. produced and U'ed. c,..pC'cially d11ri11;.; pa"t decade", as insecticide;;, fungicide~. am! yennicides I sheep and cattle dip, gra,;shopper bait. rat poison) as \\ell as a herbicide, especial!: for clearing railroad right' of \\'ay . . \r,.;enicals arc applied a,; spra1s to nrchards and Yineyards. and are dusted from airplane~ upon cotton. corn. soybean, and potato field,. They are employed a<; wood presenativ('s, in the manufacture of gla;;s, lead-Lase alloys, dyestuffs, bronzing". and paint pigments, and medicinal and cosmetic preparations. \\'hi le the causal roie which arsenic pla:s in the production of cancers of the skin on the liasi' of chr<mic arscnicism of occupational. medicinal. or emironmental origin ha<; loll~ since been firmly e~talili,hed. it is oi rather recent date that e:-.11o~nre to ar,enicals has 'eriously lieen considered as a principal cau<;al agent of cancers of the nmcous m<-111lira11e-;, such as those of the bronchi, stomach, and blarlder. Indeed. today there exists as yet onl) highly sugg-e,,tin~ hut not concJu,in evidc:nce linking cancer of the lung \1ith an occu11ational expo~ure to arsenical <lust. Howe\er, in almo~t all case; of lung cancer for which such claims were made, tlwre existed stigmata (Ji chronic ar.;enici-;m in the form of arsenic <lermatnsis, with or without skin cancers. Since the inhalation of ar,;enical dust and fume~ produce,, rather frerpttntly, the cle\elopment of perforat<>rl nasal septa, as well a~ chronic irritative conditions of the bronchi, thereby creating a symptomatic cancerigenic pattern similar to that seen in chromate workers, the existence of a can-;al relationship be-tween cancer of the ~lung an<l chronic arsenicism appears under such circumstances to he a reasonahle conclusion. Chest and x-r;1y "'a111i1Jatinn- ,.f W W()rk('r,, l'llployed in an arsenic ~melter re\ealed a mild degn( of pmumoconio,is ( 152). :\lthough Saupe hin1<10>lf rlirl n'>t rli~cr,ver any nirle11ce of lung cancer :unnng- the \\'orkeh 'turlic:<l--t'\'('TJ though they qf!l'n \11-re atllicted by hyperkerato,;es of th<' ~km and j'(riorated na,;11 '''Jita lw cit<'d tl](' a11t<JJl'Y l\lli;U\\11\1\I 1: l \ , \ I ].,'. ..!13 ,. ~. i;; ;:' .,JI'. ,.-;i:-,1 r"".1.<t-..<..il.l' i4' ~'!\I"' ~. ~.I ..,::rl!'/" ' -~'l'~~~ ~-;.. -""l.t~.:>,..:;i.:.~.~Jt,;.,,..1',,.t ~,.,. . ' l -.....- ~ Fie. 7. Squ;n1H1th cell ca1T11101na or1gi11atinl! l' tlic i1a-.,,d -...J1111 .. fqr }~ n101nh-... d1n1n11l< 'lfT r 1.tl ... t ()fa pdrti( le -.,J/r iLlov, .+ u. Fie. S ).~a----1\c 11r(Jl1f1...ratJ<111 nf tl1e l1ro1H:ill11'.;:r l'J!Illicliutn 111 1,., "'\. ,J ful , i\ t 1 l ,.:_ l !J< JI 1tJ1..., l4 J \ i11I1; Ill ll' I ff( I }11-.,t. iii a r-at ;t L!LIIJ!ta 11d1aJing pig ex- Fil .. Fl!, ti ... ! Il<' 1) .\n;.irila .. :1c 10 :---.,,/IJ,ilJJ11U-.. \\ nrkt r 1..d.1<.11Jr>111a 41i 1\i, 11:t ...al .. n11, .. t lll 1.t1 ('J!ltlf11.l \\ JJi ;1-.,ln .. ;, , 111 ;-tri l11Hli1 ... j-.1,pri,11;tJ11;] 11 i Ji, :,n 1~! rn,u1uJ-,l' t11nr i1f ;i', a .. !w .. to.., 2 J.1. \\ (. JllTl'FR oh,,,enatioth prn1un,J~ 111:ide J,_, :-;Lh1rnrl ( l .'-t 1 un two arsenic -nwlttT \H>rkG;, \\'ho di,d with c:mcn ui tilt: lung ( l /O ,. Fuur addition~1l C.bc-; ui lung cance1 111 :-heep dip \\urkers with ar~cnic dcnu.1to,,,is noted in unt~ oi these were rqorted b_, ::\ lernrcther ( 123 1. 1Yhile HopkiIJs and \an ~tuddiford 1_/() 1 obscrnd in a farmer living near a cotton field :-praye.l ,,ith insecticid1:s. ar,,enical dermatosi~, epitheliornas. and cancer of the lung. The occurrence of 5 ca,.es of ltmg cancer ( 79. 123). among only .?.+ ind11idua], <nffering fr"rn nccupatic>nal ar,enical dcrmatusi:< and cpitheliomas cau~ecl .:\ eubauer ( J32) to wonder whether thi~ is mere co- incidence, because only t\\"O casC"s of lung cancer were obsened among 1-B cases of mcclicmal ;!fsenic cancer,, of the skin ( 150), or under occupational cunditions, whether the irritation of the respiratory tract by ar;,cnical dnst was re~ponsible for the phenomenon. Henry ( 72 J. commenting un the occurrence of skin cancers among sheep dip \\'orkers < 1910-1923), recorded the occurrence of t\\'o additional cases of lung cancers among ten workers of this group haviug cutaneous cancers. He mentioned, moreoyer, the pre::,ence of cancers oi the left foot, abdominal \1all, and lung in a furnace man of a sodium arsenitc factory. A1ialyzing the mortality experience of a sheep <lip factory, Hill and Faning (7-1- J iuund that 7, or 31.8/(. oi the 22 cancers causing death among members of this group were located in the respiratory organs, while 3, or 13.6%, were situated in the skin. There were during the period 1910-19-1-3 a total of 75 deaths from all cause,,. The pruportional excess of cancer deaths was mainly attributable to an excessive frequency of cancers of the lung and skin which were confined to workers in the chemical processes and were ab::,ent among members of the general group who would be unlikely to be exposed to any specific hazard. Perry, BO\der, Buckell, Druett, and Schilling ( 137) concluded from the clinical evidence obtained that after many years of exposure to arsenicals these sheep dip workers may develop a squamous cell carcinoma in the bronchus. The most recent addition to epidemiologic investigations on arsenic cancer was made liy Snegireff and Lombard ( 161) studying cancer deaths among employees of several metallurgical plants of unidentified type. Of the total of 109 deaths from all causes recorded during the last 25 years. t twehe were due t<J cancer of all sites and of these, six were located in the .;Jung. The in\'est1gators concluded from this evidence that "there are in- dications that bio!<Jgically the human race made the adjustment to arsenic in the environment and that <llll) rardy, when a,,;.oliated with uther contributing endogennu" factor" 'uch as systemic di,;(ase, or pos,.,ihly factors such as radiatiun, it may be capable (Jf lljhet ting the liiological ('</t1ilihriu111 :" and further "that the handling- <if ar,(nic trioxid( in the inclu,try 1 _,\ IHOC\ \II\ I \L I.I''" ( \ ',, !'R .!I~ does nut pniducc a s1grnlica11t ch.111~c in tl1" c;mc(r 11 .. ,1i:tl111 11i tlw ]'lanr employees: hence other fact()r.; 111 add1tIC>11 h .tr~111ic 11111-1 111 11q,1den"l significant in the cau,al rdatiun,hip t1) ral!c'cr .. I 1: 11, 11 ',j t 1i1 f.1c1 that _::;or1; ni all cancer death, ;rn1<111g , 111l'lo_1 ('"' 'ii "lh' pbnt -11!1n, <l were cat1'ed hy cancer of the ltmg. the nh,;nvatirqi- rn.tdt in fact C< nfirin a carcinogenic action of inhaled ar--enic uio,i(:, 11;1"n tlit' ri'"llt'' "f the lung- of the <'XJ""(d worker<_ Thi-. inkrprctati";' "i the d:tta (Ii ::--;!lt'g1nff and Lo111hard i:; ~11pported h_1 the high incidcnc,. "i !ung cancer an1"ng the population of ,;en-ral cumJtie, in :-ironta11a ,,-h::rt' CUJP<T --melter, and mine~ 1\ere operated for many year' creating ;m "'cnpati<in;d and erninmrnental pollut i(ln nf the atmo~pherc and ,, iii ll'i th ;1r-enical ;_ I'rl11< llged inl1alatio11 oi ar,en1c;tl clu~t and fume,, appear,; U> pn duce an incna;.cd liability to cancer of the lung. However. the existence of '-lKh connecti(lns ,Ji,1uld J,, ackn1n1lt-dged only \\hen there xisted at soille time. clinical anrl ii J><":--ililc-. hi.;t11- and biochemical e1iclence of chronic ar~enicism. In vin.,- oi the ali~ence of any such e\idence associated with chronic ar,;enici~111 ;u11<>11g the- nick1l refinery worker,; affected by cancers of the na,;a_I c;ni ty. paran:1 ,,tJ s111u "b anrl lung, among excessive tobacco :-moktr~ with cancr-r ,,i the iarym.: and lung, Jt is most unlikely that exposure to ar-:enic dti--t. furn(,, and Yapr1r,; plays any role in the production of respirator> cancer,; in rn<inher.; oi the"e population groups. Ber\.'llium. Ber~dlium is a metal 11hich has found ,i:' n>iticant inrlu,;tr:al } use only since about 1920. It was not until about 19.+0 that lwryllium and iu, compounds were exte1bi nI y employed f, ir m irnernu-; JtirprH< ;!lld prod ucb ( lier> llium -copper; lwrylli urn-alumim111 i. ;11; d her;. lIi u m-nic hd alloy~; gla"'; pho:-.phors in tlwire:-,cent lamp~ and llhm tu!ie"; ato111ic energy product--: ceramics. refractories; x-ray tube windows: 1itreoth enamel: radio tubes: textile Ji lire,;: gas mantle~). Hanly ((>81 !1()ted a:-, a cuno.enatin e'--lilllatr- that llwre <C< 111-r, d up to Septemlwr I <JS] between 300-.+00 ca:-,c-; of :irnte hu_1 llitnn p<Ji-.rirnng and at least 200 ca,.;es of the chronic variety ill the l-nit('d Stat<, v,hich re:-,ulted in the fluore,;cent lalllp indnstry in a m<irtalitv of aliout 2S'; an1ong- the ill \\"<Jrk1r:-,. It i,; nmarkahle, mr1rt'(J\'er. that dirmic lieryJJio,;i,, ha~ ap11eand nut rmly amont:' expo:-(d wnrk"r'. h11t af,<i ;1n11111g 1w1- 'on,; living- in the iwighhorhoid oi tluonsnnt lamp ianr,rif, and i11halin;.; tlwir lwr_dliwn dil1w11h 1 -1-11, .'O > It 1s 110tt1\l>rtl11 that her:l!iurn apparn1tl_1 rice 1nlial(d i~ r<tai1wd <i\'<T a long p(fJ<Jd <Jf ti1ne Ill the h11nian )i, H]_1. llW J,1-r_1 lli1m1 <.1;,, dcHrtl"d m rlw 11n1w 11p t" ten 1c;ir, af11r, 1-":11i11n 11f '- .;1"'111" 1'I/ :nu! ha..; lwvn d<n1oihtratr-d in th<" lung~ 11i rat- >111 1:1r ;1i1"r !11r 1ri!ui:i1irm 2111 II. 11 I I. I' I I{ of lier} lliu1n O\ide ! ..j.() J a .; l 11e1 :,.:. in tl1lir hum,, 1 13. 11>5 1 whtTt' it llla1 replace calci11111. E '\Jlt'ritntnt, "i .\ lt11idge. Barne,;, and D('JJZ ( 2 I. 111tJ1t't11 er. ha1e .;Jim111 th:n her: llnm; 111n.; react rapidly \\'ith certain ti,.;ue i irotei11' and form comple\t'' 11 ith pla,111a protein.; \\'hen irnroduced into the lilnrnl. Tlw,.;c C(1111plexL'" pn >tt d the lier; llium from being pncipitated by plm,pliate ions. Ganlne1 ( 57 1 in )\)..J.(1 rq1"ned the production of o,.,teogenic 'arco111as in rai1bib mjccred i11tra1ennu,\y 11 ith in,olulile ber;. lliulll Ctntaining pO\nkrs ( herylli11n1 pho"phatc. zinc herylliun1 ,;ilicate). Other inn.;tigator;;; .,.,uh-<l'(jl!Ctltly c1111firllled thbc rl'>'ttlt" 11ith the ,;a111e and other hn:llium ,11111p11111His 1 1.wrylln11n .ixide. lw1yllium silicate. metallic beryllium) inuuduced int" rabbit> by the imral'(nuu,; or re,;piratory rontes ( l(JO, 1-t. /(., l 2CJ. IS. -J.7. 13). The i ireparatory period for the sarcoma 1\as iro111 11-2-J. 1uo11ths. Co111111enti:1g on tht suc<e,.,sful production oi osteogenic sarcomas in raL>bit::; after inhalatin oi beryllium O\.ide. Dutra, Largem. and Ruth ( -J.7) noted the fact ab" that the hones of persons dying \\ ith lier:llimi.; cnntainc-d 11ct i11cn11~irl<-rali!e amounts oi her\'llium. Barna rd ( 12) ancl Dutra t'I c !. , -+7 1 suggc ...ted that osteogenic sarcoma from e<1lllJlOUntl~ of ])('ryllit:P1 "might v1,:=;il1ly lie another indu:-trial hazan!." In l l)..J.8. Hucp<T ( 87 1 prop hed that the ,.,arcuid pulmonary manifestation' of lwrylliosis might lw fr,lJ111'.erl l1y outright malignant Je,ions in the lung,.,. The recently reported succes:-:iul prc1d11ction of hronchngenic carcinontas in the l1111gs of rats \\'hich inhaled o\er periods of more than one _:.car. du,.,t of ,.,:1lt1!1Jc. and i11snh1lil< lJCrylli11111 cnmpou11d-; ( 17K l make:; the ;1pp(arancc uf ,;nd1 delayed m;iiign:.:Jt "equdae in man a di,.,tinct pus~iiJility. C(Jmnwnb on Jfr... piratury .:dn;tl Cancers. The eYirlence presented cktnonstratcs that ,.,rmw metal- an<l nwtl compounds when inhaled as rltht'. forne-,, 111i,t>. r11 1;q11Jrs are capal1k ()t producing cancer,; in Yanous part-; ui the 1-e,11iratr,ry tract. l'rntmF1coniotic chang(',., pre-cede and acco111p;my ,;uch denlop111('nh ll'h('ll chnm1itt111 compounds arc inhaled. \\'hilc -11ch le-ion,., haYe not been n1ir,rtcd iollrm ing tlw i11!1abtion of nickel compounds and arc :1ppare11tly oi minor nature aitcr the inhalation of ar:~cnicals. .\lthot1gl1 the re~pirator,:. imr<Jduction oi beryllium rnrnpotmds leads in animals to the d(\'tl(irnwm (,j pr<1!!n,si1< !!ranulomatnth pn<>11moconiotic alterations \\'hich rn;1y l"c<Jllle cimplicated in rat.;; liy lironchi11g-enic carcinomatou,., manii1.-,tat11rn,.. m' such malignant c,cqnelae ha-; lwen reported as _1('( in lrnman lwr:lli(J,is. \\'hl'tlwr or not n,.,pirat<Jr_1 nwtai c:u1nr, 111a_1 d<'l'll11p :ift<'r tlw inhalation of otlwr metal-; npn,<nt- :1 )'r11l1li-m i]e,n ing -,t'rt()tt' c1111,ideratio11 I.\\ I I~< l \ \J I \ I Ii I l \ 1 , l \ \ l I Ii _: i,- c-1cciai1 11h('r" -uch nwt;il- :trt 111<kh tht'<I r li:i1 v :1tt:t111c'<l :11.11"r in.iu,.,rri:d i:111.11n:111,c 111111 m rt ct 111 '.c:1r~ ]'>'.J:l.\111>\. (IJ' l.\11\l.IJ/(I.\ .i1 ;-;li/tll\ .\\!J ('\l{/lll\' l',.!l'l'l.1'' 111 l\.1:,1 11U I(1fn (,_' \ \. L'!-.1! Tlw -vc1>11d gr"l!J! ()f IT'pirat(lr_1 carl'illt<.'-:l'll' j, l'()Jl1!""'"1 11i cht-rnicil a~!yl1t .... i1} Ldher 1li\<T'"-<" CIJt11jHhitiP!1. 11l1! -.,haring lht I,, lLtT.tl'l('ri:'.'lit...' tlttt th<:_\ m;ty form <11' c1ccur a.; ]"'!:mer' Tlit- prin,iJ>:t! ,., '.l''il'l' 'll,'-!g<,t;il'-! tht ,.,i,renct (1f "p()l_l'llltT c:;l!ll'er:-" k1-; u1111t in1111 l''J11'i'1l<lll:il 11J1,,n;,ti"1h. Tlw ,,1, iar kn()\\li (>r :-tl'J't'l'tl'd ,-arcirn1gt11ic p11l_1 lll< r' :in citl11r pnlntKTIZtd carlH 111 t'<lllijHll!ild.; or :-ilicon ''"illjH1t1nd.;. Cane' 1 11i the n,piraton tt an in :1n11 '\'t'lll ((> he ,-a11,;1l1_1 rel:ttl',1 ro horh 1anccit... .,j p1ilymer can-irn1gen, J,opr1_1p_l'I ( >i!. Through th( ncent di'c"HT_I' (If cancl'r' ,,[ tlw parana,,al ,.imtS('' lar_1 IL'\, and lt11:g among i,opropa11nl 111a11ufant1n-r-. the oc- y,,,c11rrull'e of c:arlJ1111-pol_:.111cr c~ttKer,; ha;; prn1Jah11 h<'ell t"-:tc-ndcd 10 man. 11:rr11,_1 I rJil. i.e .. the l'rlldc liquid irom \1hich i,.,1,1,n1p_11 ak< ,Ji, ii j, di-.till(d. and 11hich j,; a ,Jightly turbid. Yi,cous iiquid. turnin~. liJ' ll ,tanrling. ,,)(v:ly into a Jm,11nioh to 1Jbcki-.h tarry matenal. contams pnly]irnp:- kne co111;1ound, a' 11 c-11 as propylene ('ther 11 hich may lw ri:--.irlized into pro!J_'- lenc- peroxid(' and prop_dem- ('jl'Jsid<C h;t1ing a tentlenc: t, 1ir1ly11wn7.L'. IJ(,lypropylene. 111erchandi,,;rd as ( >1,p011nl K. is u.;rd cn111J11crc1ail:- a- an uil fr,r ca!Jle filling. \ \'orker,; en1ployed in iq1pr.-1panol manufactllre ha Ye been t'.'\po;;ed tr, the inhalation of 'apor;,, 111i,.,t. and dn..,t ()f j,,)propyl <1il. P-caping irnm leaky pipe cr1nnecti1Jlh, ddt,tin JllllllJ" and ga.._J,th. 11r ,pilled r111 the flo<Jr at the occurrence uf lJl'eak-. in pi]idinc' and duri11g rcpair, rin ]'IJie~. f>UlllJ'" and ,,ti]], \\'<ii, Smyth. and Xal(' ( 183 1 repurted that IWL\l'l'<n j(1.:?1-.: awl JC),~0. a t1Jtal (if -.;nen neopla~m' affecting 1ari11u- part;, oi the respir:1t11r} tract fn;i,.,;tl ,jlllh('" 1fo11r1. lannx (t1:"' anrl llin;_; (rnH1/ GtnJt to ")J,.,en:itilln arno11g /I e111plo_1((s or in 1'-' ...J'; whi 11r,rkul mire than ii11..: ye;u,., in the i:-.01m,p;,nol phnt (Fig. q 1. Sin('(: th(' occ11rn-ncr.- 1,f ;, n e '-Cr:,,,i n n11111 li<T oi n"r ,i ratory cannr:; alll:in:; i,,'Jlr< ,p;m1J! ma 1111- iacturer' ha,., nut lwC'n limitf'd to one particular plant. it cu1 lw \"iIJc!llll<'d that i,opr1Jp_d oil. and thth P"''i!Jh polypri1pyl11w c111npJ:111l-. rq1n ,( ;,; a !tu1nan carcinqgnl. ,\ .. Jw-t 1 i-i,. _\,Jw,1"" dilfrr, fr11111 tlw urd111an ;;i:lllt 1111.!('(:11i:tr cn.;tall111' ,,ilic:ltt'-,, llit only in ih cllt'111ic;d and 1,Ji_1 '1c:tl J'r<J<t ;i(''" IJtlt ;iJ,,, in tJ:,~ ;rinatoniil:d ;i .... pe<'t" <>f th(' ptH'tll1H>c11;iir;-.,j-.., 1Jrud11c,d L~. 1t in (!JL tr:1 .... t 111 :11( tr1rli111(11 .... 1(111;tl J>11l_\ 111( r1 "< 11 -....i!1{,i t'r\ "1.11" i11 .' J_ 1( l; !11 1\.'~r'il ;11< 1:1.-... arc 1l'it c111r~1ng ch:1rgt...., t11 :1ttr:1lt 1'~1 ... 1t1\c JiJJl'. ;i ... 1H..,,fri,._ ('11n .. r-...t"'l l !." \\. l Ill Fl'FK of gia11t tihr"u" n111lnult" l'tlllljhh<'d of ]'"!_\ rneri,~cd ,.,jfico-o:-._\gcn ktrahydra which ~m arr.mged 111 d1a1Ib "r hands. Canad;, furni,Jies aliont I 5</( of the \\"lild production ,,f ashe;;tos. C:rnadia11 :i. ,] )t".;tn~. l iecal!~f' ni ih long fibers. 1> e~ptcially suit:d1lc- ior textile,,;. The cu-exi:otenu' .. i asliest \\ith cancer of the lung \\'as first reported by Lynch and S1rn th ( 11.~ ) in 1935 (one case :. who record eel later three additi()nal cases 1 11-+. 115). Similar ohsenations han: ;;,nh,.,eqllently he-en 1-ecu1ded fron1 1l1l:' l-mred ~rates (/7. 7~. 'JJ. H>6); Canada (30. 38. 149); England ( 3<i. 5<1. r.o. 12-t l; Germany (9. 20. 21. 81. 10(,_ 13.+. 18-.J. l. To this number rn11't perhaps be added the eight cases of cancer of the lung complicated l>y a~hesto;;is which l(enna\1ay ancl I(enna\\"ay (96) discoyered in an analysis of the death certificate,; of males registered hetween 1921 and 193~. ancl the series recorded by \ \'~ ers ( 188). There \\"ere 37 males and 15 iemales among the 52 cases for which information on sex was available. The male: female ratio is thus 2.5: 1. which represents a marked shift toward the female side "hen compared with the usual sex ratio of 5: 1 to 10: 1 for lung cancer;; of unknown etiology. Equalization of carcinogenic exposure as represented by asbestosis. for the two sexes, thus resulted in a trend toward equalization of liability to Imig cancer. Additional support for a causal relation between asbestosis and cancer of the lung is deriYed from the fact that :\Iere\\"ether ( 12..+ J found among266 cases of asbesto;;is ohsen-ed from 192.+-19.+6, 31 cases of co-existing $ancer of the lung- ( l 3.2j;( ) , while there were 91 cases of lung cancer \vith an average age of 59.4 years among (),88.+ cases of silicosis ( 1.32<;~ ) . which came to autopsy. \\'edler (] ,'-\2) noted that asbestosis cancer of the lung occurred in 1-+ cases or 16<;~ of 92 cases of asbestosis on which necropsies were performed. whereas the normal rate of lung cancer in autopsy material was estimated to be 2--6~1,. (Table XVIII-41a). The histologic types oi lung cancer,_ observed do not bsentially deviate in their relative frequency from tho-;e seen in cancers of unknown etiolog_.,. There were 22 squamou~ carcinoma<> (Fig. I0 I. 7 oat cell carcinomas. 4 anapla~tic carcirv1ma<>. and (1 adenocarcinomas. The evidence on hand has convinced the \\'est Cerman Government to make asbestosis cancer of the hmg a compensal.le cli-;ease ( 169). lnmnwnt'- <>!1 H.epir:ttriry Polymer Ca11Ler ~- \\'hile the fundamental concept of "polymer canc<-rs" is a tentatiye one and neerl-; t<> he supported by additional (1-irlence, the a 1ailable data are su ftlcie11t ly important to require ~erious attention fr(Jlll l><Jth a scientific and practical 1ie\\'poi11t. The rapidly e:-.pm1rli11g ind11>tria! pr<iduction and imlti:-.trial and ge11tTal 11se of n;it11ral ;md '_vnth<"tic j>rJl_\ 11ieriz(d ,ulJ,;tann~ in pJa.,11c,;, 111111'. I '.\\'\l\(lX\IF'.\ I \L 1.1.\,t. \ \\,l f R .! I :,;,i, n -r\HIF X\111 ldllrt'S ,,f f)tuth .l111r111,; l/d,'( .Jrr'i~,i/,)1 111,,.;_.(~,~, c',imf'ar1~d lt..'I! tlzc' .lfurlofuy /'.,xf'tnc'ft('t' 11j .iii 'JI !:1::!1111d l 1.d if1\1'11. :\ti Can'e <>i death Xu ()h ... (rvc(l Lung canc<r" l l Other re<pirat0ry di-;ea,;es ( mch1<led pul- monary tuherculn>is) and cardicna<cular ji .. ea:--es: ,1{ \);:;1th:-- 1->. )1('(.'[t:d 'll E and \ \". !-ate" OR Te't (1f "lig11it1can,~t". c''. d1ffcrcnce })e~ \'- een uh.. e-r\ -:ti .u:d expected I\ :t!uc "f P <(1000001 I\ ith mention of a'besto,is \\'ithout mention of asbestosis > 14 - () \ 7.o j IJ.001 X eopla<rn;;, other than lung cancer .j .-\Ii other dt'>easese .j .-\II cause< .19 _}_ ,') I 4.7 f I 3.4 <O.I < 1.000001 ''R. Doll binciud1ng one case with pulmonary tuherculosi, <'Including two cases (benign stricture oi eso;,hagus and ;'besto<is was present. but was not thought to have hel'n a death ,epticem1a) in \\'hich c.-ir11nh~1tory cause of rubbers. textiles. synthetic plasma ex1,an,Jer,, etc.. brings a considerable part oi the \1orking population in direct contact with chemicals of thi~ type. It ::.eems to be advisable, therefore, to study these population group.; during the coming decades for the occurrence nf cancers. particularly those affecting th( respiratory sy::.tem. HELATJo:-.- OF J:-;JIALATIOX oF Co:1nn:sT10:-: .\:\I> DrsTJLL\TIOX PR011cc-rs OF CO.\L :\X!J Pf.TROLEC~! TO RESPIRA"IURY CA;>;CER The third major group of recognized. q1spected, or potential occupational re;-,piratory carcinogens is compo"ed of substance, co11ta111111g ;,pecitic carcinogenic aromatic hydrocarbon~. and !wing- rl<-ri\(d fron1 the incomplete combustion, distillation, catalytic cracking an<l hydrugenatiun of coal. petroleum, shale, natural gas, and similar carbonaceo11<> matter. The carci1rng-enic hvdrocarl)()n<; are e,;p<'cially contained in the higher boili11g iractions of coal tar. pitch. creo~qte rJil. anthraccne (Ji l. soot, carbrm black ind rJi!,. luliricating (Jik :ind crudl pa:-aflin <ii\, The ir1h:tlati111 !i rlu~h and m1,;h of these mat(riab n,t1lt, in their p:crt 1al re1<11tir111 in the lllng and in the pn1duction of anthrac"I'. l1iturni11i-i'. <r d111111ic <iii JIWlllll< 11JI:t t 1111lnt>tion and 1>i.tillati(Jn l 'rodt1ct, of Co:tl T!w :ipp:innt 111- .Z.?U \\ 111 \.I'\\{ noc1Hll1"l1C~:' nf i..'11aI :<~1d p<.:--.:--11'!~ -~r:tphitc dn-...t ~l"' rc:---p:rator: ~an.:inti~cn:--. is n<1l ,..hared 1: the i1l<'t'1lllpktc c11:n!,u,..tion di,..tillation and hydru.~vn:1t;llll pr(lducb oi C<':t; 1 pnch. r;,1. s11ot. CTt'1l;,<1tl' ',j],, ;m1hr;1u.11e uil'. cir oi],, and the highl:> 'i''-"'ll' tiilY and tarry iractiun~ ul1tamed ll\ the direct h_1droge11atio11 C<i C<>:d cm]'loyed l,_1 the Be1g1us prrc<~, 1. J\ecent o1'"''rYation,.. made am1ng gc11eratur g;;,.; oYctJ \1orkers in _I a pan. Canada and England ( 3:'. ~l. o,=,, ('ti 1 indicate that ;m c:-,_p<..,ure tu coal tar i1111ws prudun,; a11 c .-..:c1,,..1 H" Ira I1ih ty to l u11g cancc-r. The JaparH>e in n:,..t igator" funnd \1ithin a 11_1 c<tr period, 21 c;1,e,; of hmg cancer a11Hmg genc'rator onn \\orkers. v.h> svre l'"Jl""'d tn 1he inhabtion of hot tar itmw,- \\'hen stoking the coal. .\n c"ce.._,jye Jung cancer r:ttc \\':is absent among \\"1>rkcrs ernplo_1 ed in other part:' of the ~tlel milk The general im:idem:e ni lnng cancer among the: generator gas \':orkcrs \1a.:; 5/ 1.000 \\'(Jrker,; employed. St,cn of the~e 21 lm1g cancns occurred in \111rkcrs ..J.O year.' or younger ( 33r;. again,;t 1,-::r;. in cryptogenetic lung cancer" 1 The l''.:]Hl~tu-e tnne yaried from q _1c-ar- to .2-1 _1t~ar-. the an-rage ]wing lo.o year,. Similar oh.;cnations were rn:cnt ly rnade ;i.111cmg Canadian g-;t,hou,c \1 orkers. Of J..j. cases oi canccT :tln<111g retort house \\'Orkers. ;;j" \1erc due to cancer of the lung. nn<- t< canc('r of the laryn" anrl one to c;mc::.T of the ('thmoid sinuses ( S/r~ ClllC<:rs of the U]J] 1\:r and Jo1wr re;:cpiratory tract I. It i" likely that ,..imilar lung cancer incidcnce rates may e"i't rimong A.111<-rican tar \H1rkas. FollrJ\rm~ a Yisit \\'ith a tar distillery \1hen", among the 300 workers during an 8-ycar perind, some 25 ,;kin cancers and more than XO pitch warts had been fJlJ,erved. there ,,as found one case of lung c;,mer. :-;ub,..eqmnt inqui1ie,; made !Jy compan~ (Jfficials brought the mu11l1er oi lung cancer,- in this and other tar operatirm<; to 6 cases of cancer of the hm~. :-:imilar e"Jm,;ures e"ist for the carhon electrode workers in aluminum production plant,;, \\'h('re \\Orker,; han~ de\'elOjJed cancer,, rJf the skin a-; the re-.;ult of contacts with petrolenm '"c-arhon" tar fume;;. Frum the evirlencc available. it appear-; that the inhalatin of tar fumes str:,taincd by \\()rk<:r-; oi certain operation'i (coke O\-cns. g-eneratr1r gas plants, gas plarns, t;,r <Ji..,tillnic~ 1 seem to have an c:-.:ce,,i1e liability to .cancer of the rbpiratrJry tract. l l is not unlikely that a more thr1rough ;and competent arnt!ysis of the d<:'ath rt'C(Jrds of oth<'r \\'ork<'r groups, 1d1ich ban "o ;;lr );ccn i1,m<rl tu bcl.. ~u.Ji lc111kH~il,.,, 111igln <:.\.Leud the t_1 p<'" and rn1111J,,.,r r,f tar and pitch 11orker.. ha Ying an al1111.rrn:tlly high re-pir:ttory cancer rate. l\troln1111 and :'hal<' (Ji!. In ;,drJiti<111 t<J ,kin c<1111act \1ith tarci1111~<'nic p<t1-. ilt11111 dcri\at in, man: \1 ori-.i-r, arc ah1 J ('" po;,l'rl ior "ccupati<mal rca-on~ to an i11h;thti<i11 ,,f <iil 111i,t ur f1111w, ( \\orhr,., in parat'tin J>1l~,i11g I '\I I i<I I\. \ 11 \. I \I \. 1, \ '.\ l I\ ~-' l oprati"n'. c'<Tt:1i11 ~r<illj" ,,j 1111 n1i11cTy l\"ktT'. 'i'1111wr-. nwtal Ltti11 \n.irl...(r..:. f,1~111dr~ \\orkcr". :11(t:dlurgiL-:J \\ 11 :-ker'. ~1 1 -111tcr"'. l'tC 1, !n spite oi d11~ <'"talili,..l1ed <>cc111:1t1(111al rt-1.ira:,,n t"'-1" "ilrc tll pc!roln1;n <!lld ,..h:1k uil-. it 11a, 11111:; 1tn11tl_1 tl1.1\ ll'." ": 1lirct c:~'t':' 11i 11n1patilU:ii ull pnct1111{~n1:1 ~t1111~n,~ "'th:h \\1lrktT-.; \'.\'!t ~~.tl'l'd i1~1 rlcnnl. ;dtlH,l:'....'._11 s11d1 c<>11diti<111" lia\l' rathc1 ir<.1m11tl_1 li.T:l 1il1,crnd ;iittr r<J>l':i~c-.l medicinal i11,tillati<J11s 1Ji rni11l'ral '.1il c11llt.1ini;.: na-;1! 1ln1J" 1nil a,..p1r:tt11:1 ptHu111u1111;-:;, or p;1ralll111:i:11~ ,,f tht 1u11~ 1:, :,u,-t. l\\,, t..'.i'""(--.. ut Laih. 't r oi the Jun.~ appart'n:l_1 d:1c!11,in..; on tht 1,;i,;..: 11f :1 11,cd1cinal mineral .-.:: p11eu111unia ha Ye lJccn dc~crilied (] ,:; 1. 1;-;_:; '. The ocn1pc1tiunal nidcncl'. :ll'aila!Jk ur pnh!1-hed 011 thi~ ~t,..pect i.; rathcr scanty and in part cn111nnlr,,.1al. h:e1111away and ](v1111;!\\ay I <i() I found a relatin:ly high ratio of laryngLal, lint !1(t ni pulrnu11:11-_1 cancer in n1uk spinner~, \\'ho inhale a spray of carcinc1ge11ic sl1:ile oil lulJricating the spindles. Southam ( 167 J noted that mule ;;pinncr~ ncca -ionally deYe!op multiple primary cancers in\'ohing the ~tumach or the lung in arlrlitinn to cancers of the skin. ::.;cutt ( l.'i7 l, on the- other hand. stated that he had not obsernd a ;.ingle case ()f lung cancer among ,hale oil workers. rn Huguenin, Famet, and Bonrdin (91 '1 ,,ho analyzed a ~e-ries of l 1.2 lung cancers for possible etiologic factors. foun<l that or 16% were metallurgical \1 (Jrker:; e"posecl to the inhalation of nelnilized lubricanng and cntting oils, eight were chauffeurs, h\e mechanics. and one \\'as an engineer. They concluded that their olhtryat;r,ns indicated an cxcc<;-inly high frerj11ency of lung cancer among \'.r1rkc-r~ c"J>O<;cd tr, Yaporizerl r1r nelmlized lubricating oil. \\.bile the study of Gafafer and Sitgreaws ( 5()) on cancc-r morl1idity and 111ortality amrmg- the male empl(Jyer:s of an r1il refining cornpany clid JJ()l rneal a11.\ aliwirm;,] lialJility of the mc111lwrs oi the occu11ational group to cancer uf the lt:ng. thi' j urlgment may have tu be revi~ed at lea;;,t for cntain types of ruinc:r_1 wnrk<r<; according- to m:ire recent and scrutinizing oh,crYatir,n'>. J<r,<sch ( l +5 I ol1~ened three Jffi- mary canccr" (,;kin. 'itu111ach. arnl limg 1 in ;, paraffin wurker. Tnurainc and Hmrr ( 171) al-.n attri!mterl the rkn]r11111wnt "f pul111<1n;iry cancer amoJJg certain workn grutI]l,.. to lubricating iJil rni-t". Such l'"f"J,;ure condition .. may acnit111t ;i],,, for the e"ce,-;i1t iung- callcrr m<irtality a111rmg male metal gri11d<'r., ol ,,('fl('(] I1y Turner ;ind Crace ( 171 1. In 01w hn~< .\11J('ric;111 <iii rl'flrwry. tlir- "11ll'lo_1<e'i ,,f tlw J>:ir;tffll! ur-- ing- op<'rat1011 ~lm1\<rl nnt only a high!:. t"r~..,j\( incid<'ll<'<' nf ;;rnital cancer and iurr1i,!wd .t.) ;-;, ; "i all <antir, r.-c<inlt-d ;,11111nc; ;di 11 <>rki-:,, hut ab<1 51/; ,,j all it111g Ctlll'<T,, ;dth><Uc'.h 1w_1 n11r,..,<nterl about 12' ~ oi tlw t<1t;d 11 1rktr I" 1p1ilati<111. ~ltl<..T ltj} ...,1111t ;t"i ;1 \\:l'""(t cir ('r\JJllllt'f1 ;LJ J,;(idllC1 J):~"-i J,(fn fq11111] 11~ 111 ) ) ) II. l'. 111 Fl'Ell earci11cgc111c anrl to C(lllt:1m known carcinoRenic hydnira1hons. a thur<1tt.c:h and Clllll]'l'lt'lll :,11rn:y lf occupational gn>nJ particularly exposed 111 the inhalation of ,;oot ( 01wrating railroad personnel. stokers. cl.l'h"n l>bck marmfacwrer,;. nthher. paint and ink lllakers. painter,;, soot burner,;, printers. diesel C'ng111e drinTs. el<"ctrode mannfact11r<TS. -;mudge ptlt 1perat r". phonographic rernrcl makers) i,, an urgrnt necessity. Comments on Respiratory _\romatic Hydrocarbons. .\t the pre.;;ent rime. e'q1n.;;11re tn t<lr, pitch. a:-pha!t. hca1y fuel oils. luliricati11g and cutting oib, ,,oot irom domestic furnaces, incin<"rators, industrial po\\'er phnts. oil refinerie,, steel 1ilants, metal smelters, carbon hlack factories. oil dumps. and smnd;.;c pots. as well as to the efflu<"nts of diesel and gasoline engine.;; reprt>sents the most ,,idcspread occupational and environmental comact with carcinogenic material. Since our ciYilization and rconomical life has been built around the production and use of the basic carbonaceous substances and their deri \'ati\'es. it clues not S<"cm feasible to attain complete protection against exposnre to th<"se carcinogenic chemicals "ith the preventive and proph~lactic engineering and sanitary measures practical and economical at th<" present time. There is, J1owe\<"r. no doubt that a great deal remains to he donr in this respect a11d that we are still rather far removed from having the maximal amount of possible reduction in exposure to the re;;piratory cancer producing hydrocarbons contained in the various carbonaceous substances mentioned. RELAT1ox oF r~IIALATrnx oF H.AnrnAcTffE Acr:xTs To REsPJR.-\TORY CA:'\CER Up to some ten y<"ars ago, occupational exposure to radinactiYe agents was limited to relatively ;:,mall groups of industrial and professional workers [miners and refiners of radioactive ores. industrial and medical consumers of radioactive sub;:,tances (gas mantle m<lnnfacturers. luminous dial painters, radio tube makers. physicists and their assistant'>. r<ldiologi:-,ts and their assi:,tants)]. Since the advent of s11cces-,fttl atomic fi,sion ancl the ready production of synthetic radioacti,e suhstances, the number and variety of indivi<luals who have occupational contact with radioactiw .: matter ha,e rapidly and greatly increased !uranium am! thorium ore mim:r::., ::.uielter~ an<l refinery workers, atomic energy plant employee,, military personnd, agricultural. hiologir. medical, chemical nH:tall u rgic. oil, pharmaceutical, and <Jtlwr indu~trial research worker,; employing radioactive isotopes, as well as operators handling directly or indirectly .'it1ch materials or tecl111ical dt'vice.., giving off ionizing radiation I radioact 1n J:\llJ<t1'-.\Jl'\.1\l I.I'\,!, l \\<IR _) _) ,"'I ,;tatic elini111atu1.., 1. '"\1:1.c:e di-1 '"'al \1u1kcr,... p:q t-r. and lt"\l!!c !l1:111t1- iacturer>, dl' I J The "111:1!a 111ctallnr11111" C\lhll''-! .J( .ttll at an earl\ agt oi the lll!IHT" Ill the ore 1111lll!ltai11:- oi :-:;a:\<ll_I \\;,, tir,..t <k..,nihed hy .\gricola 1 11 dl!rin.l; the early part oi the :'ixttc111h ctntur_1 .. 111d wa,.. >llh,..('Jnentl_1 rne11t1"1wd hy other inYt'~tigator,;. Hu11 enr. it \\a,; not 1111til lK/l/ that it,; malignant neopla::;tic character 11a.;; cnrncth rt'<'<':-'.Tli71'd 1rll'l1 ( F1g 11 I. Thi,, jwlg-ment was ,..ul1seq11ently conrirnwd 1 t\. g-10. I~. 23. 2.'. -1-0. og_ 103. 10.::;. 131. 1-!3. 1-l:-:. 15-l, 110. 11:'. l~l - .\lthough the mintr, "f tht' urani11111 ore mine-; in oachim,thal 1Czech1Js]u\'ak1;i l abo \\'ere suffering from ;t fatal lung di:-ease similar to that uhscT1ed among the Ct >halt on 111111f'rs in Schneelwrg. ~axony. it \\'a:- not until Jll2(l that the cancerous naturt of the pulmonary disease among these miners l\'<l" recognized ( 111 1-\dditional confirl!ling e\iclenc<" 11a, prO\ided later by Beutel ( l 7 1 : /'.iel ( 189) : Sikl ( J591 : Saupe ( 152) ; Peller ( 136) : Pirchan aml Sikl ( u.~ I : Haader (10); Behnunek and Fort (1(>1. Evidence ,,npporting a radioani1e origin of the lung cancers among these t\10 groups of 111iners was proYided by the nh,;enation of lung cancers among employees r,f radium refineries and radium lahoratorie,;. LiJwy ( J 11 1 reported the occurrence of two such ca,e;; among th(' workers employed in the laboratorie,, of the Joachimsthal mines. "herf' the orC'" are refined and the purified material is tested. One of thC' ca",; had chronic radiodermatitis, leukemia. and lung cancer. .\ similar (Jh~enation was recorded by Teleky ( 170) and Xeitzel (1311 in a German technician of a radium laboratory. The cancerous lung wa,; found to be radioactive. Four ca~es of ltmg cancer ha Ye recently heen r,Ji:;ened. ~KC< 1nli11g t<> Baa<ler ( 10 1. among the worker~ <"111Jll()yed 111 the radium ore proce,sing plant in Belgium. where the occurrence of "uch c11111plication,, were pre vionsly said to be alisent ( 117 1. Perhaps the developmrnt of a bilateral al\'eolar carcinoma of thl' lung in a wuman l(J _yC'ars aiter the intravenous injection of 75 cc. of thnrot ra~t may alsn supply c;11gg-e:-,tiv<" ni d('nce by the medicinal u-;c of rar!ioacti,e matr:rial arrested in the lung. :\kntinn may al~o be made in this connection of a report relating the occurrence of carcinomas of tlie parana-;aJ sinuses in three luminous dial painters. The dial painters not only ingested radioactive material which hccamr deposited Ill the bone'> and produced there the dndopment of osteogenic sarcoma". but they also inhaler! thi~ rnatt<>r ( 7). The attack rate oi lung- canc<'r an1"ng tlw Schn<Tlwrg 111iner-, ha, L'(>!l,.,i,,tently l>e<n l){'t11T<'Il /~and,'-:()'. ~inn l!-'7<J. \\'hih that 1>f tl1t )llachinh thal rniner., ha:-, lw<n :-tat(',J to range im111 -+O ~()',. altlio11gl1 thi' l!lcidl'!lt'l' rate 111ay l)(' too low l'lJJ-irknng liH rTr<nt ~tall'llH'lll oi H:1ad<r 22-1- \\ . I I I I "I I~ (10) \\'ho nuted that durllle,: d1l' J'<'ri<>d J<l3'1 ]'l_f.), :t t<>tal "f 1~0 ct,cs <ii lung canc<T 1.1t1c :tck111l\\ !L1 '.~ed :t' C< 1;;1;c11,a 111v '1,c'lq>atirnnl d1:-t'a:-e' and that in JO.!<) thtn: \\'CTC' 01:ly .:::23 11:irkt"' v11111!,i:1\ d at Joachin1,thal. (\,11siclering the iatt tl1at the l''\:j '"'urt :t1hi la!t Ill pni",J of lu11.~ \'a11cn in Juachimsthal 1ni1wr,.; rangl, inim i3-23 yl'ar,, it may justly hl' ac-'l1111ed that thl'sc lung cancl'r ca"''' "riginated in a miner JH'pllbtion nf approximately 300--1-00 mcrnlier, \l<rking at tlK:'l' mine, lwt\\'l'Cll JIJ:,?() and ]\JJQ. The <"-:pn,11re :me! btt1:c ;. ri"d :t ~cL11"tI" rg 1, ,L,itnl to 1ar_1 inim 15-18 year~ iur the maj11rir_1 ui the c1"c"' hut t<l he occa,ionalh as ,Jiort as seven } cars I 10. 1--1-2 1. :-Iea,.ttre111em s of the 1ad1, 1a~t i1i t:- of the ~chnvtlwrg and Joachilll.-thal mines haYe den1cmstratcd th:it in hu1h places. mint: air and du~t ha,c an exccs;,i\'e degre~ of radiuacriYit:- "uqa,sing many tinw-; the ma"i1,1al tolerance dose [Joachim,thal 30 times ( l.~. 16. 103. l 12. 136. 1.-J.l. 1113, 172)]. Similar, if not cnn rn01c ~crious expo;;nrc conditions \'Xi~t in most of the rni!1es sitnat<:d '111 the Criloraclo Plateau \\'here uranium ore miners inhale not only radr.111. 1. iut it~ ;;olid daughter element:; and e\.crcte polonium ill the uri!le 1 31. 163 J. J Kahlau and I\ajcwski 1'9-t J and Schraub and Kahlau ( 155 J suhjcctecl mice to the inhalation oi nd, m. :-rany oi the aninal,, dcvelored hmnchial lesions characterized Ly an ;ic_qJical epithelial lining a,.; well as pulmonary adenomas (in 7 of 12 mice ,,f the tc,;t ,<ric~. against one in the control series J. \\'hi le they ccmclwkd from thi-: endcnce that the radioact1\c origin of lung cancers in Schneehcr.c,: and (Jachimsthal miners \\as coniirmcd. it seems to he a<hi,.,a!Jle to con-;irJer the eYidence obtained by these in\'estigatnrs as highly '-Uggc,tiye but nrJt c"nclu,;iye l1cc;m<;c great yariations in the incirlrnce rate of lung tumor,.; occ11r a111ong different groups of min belonging to nornnlJrcd o,trains. ::;imilar uh~enllio11s ha\'C lJt::n reported by r ,()f('ll7., Heston, E,chcn1Jren11er, and Deringer 1 J J(I, ;i, \1-cll a' li_1 Ikn-,ha1\. J~iley, and :-;taplcton (731. These inw:01i:~atr,r..: found that mice CX]HJ>('(] to ioni;:ing 1rl111lc bod\ radiation n-Yeal<d 111 addition t1J leukemia and 01arian t11n1ir' an incrta;,c in the 1111mbcr (.1f pnhwmary 11e1Jp!a..:111s. Uf greater ~igni:ic:mce in this comwct1m1 are tlw tinding-,; of I ,i o;cr> and Vinke] ( 107 1. who found in rats inhaling :in aero-,r1l of radir1acti\<: cerium. nwtapla,;tic, anrl neo- plastic prolifrratioth of thr- l1rr>11chial <1Jitlwli11111 C:.i111il:ir ,.,., .. li,, ".'<Tl'. u!i tained \\'ith plutonium liroug-ht intll the lung~ ()f rat'. :-;ime uranium ore miners inhale not onl_1 rad<~n ;lTJd radium du~t. but also uranilllll \\'ltich may lw rctain<'rl in the Jun~-;. Jfuqcr. /.twfle, )_ink. ancl J<,hn;,:m 1.'l'l1 injcct('d mctall1c urani11111 J,r,11 clcr di,1w1ed in lawilin int<> the pl111ral and i<'moral Gt\ itit's oi rat' and <J]Jtairnd ,;1n:()mas al t lw ,ju" of inj<'c'- I \ I I 1'<1 \ \II \ I \I I I \ " l \ \ < I 1' ~}. .~ ~.. '".t \.'; "!. -' "~ ~ "~ :l ,_.Pl( . , '\<7,_~-:~-. . . ''lJr( ,.,,... ~'!.k"I",".'-,/~i.,.w. ,.c. l~".~t::. .__ ~',;,"'ti< ~ r~ . ',',),'t,;-\i': "' ... " " ..-'. ~ l '' . '.l :"\Cl I~ J.j[,'"~ ,;4. ti,._r,, 4';.:.~:,,, ,..~.1;:~ _,-~..;,;., ,t{.,..,, ,"..-.r., ' ,.,.,..:.....-..;~./. ,!!' ... ~h"<,) , . ;, r ;. . . :"' " .. {::.",t:-..~-,~( ~ ,p ~. : . , '.1 ~. ,. . . jf/f 66 , 'ti_i"';,t'~~.- ~.<_1 ::;:~ :~: :1 """'1!t},-t.>, ,' ., a. 1' ' f'..r/ t..,,. ...... ,/.J 'l__,,.._ . j , ~. I7' ., .., ,/I' "' . ,.'/:~;"~;: r ,...., . ; 11' <;" 13;_~ "'';, " actFivi.e,, n11111.H: .... \ antapSJrah,1li1ccchcearn,iri.110~1a1>1.aul"l)i. tJi,. lung oi .t cobalt urt !: .:J<'r uf rt~t. r;~<:i1- Fu, 12. X-ray picture of a boJJe f()rtning "'-,trc1111:~l of tilt fl r11ur ,,fa r~.t j,iJif1Wainngd tahrot uiruntlraitli:l'em(tJurmal ordep<Y... itHJll of po\\-d<'red nw1alli1 1ir;u1iun;, ..-: :tJ:c 111 1-it11111i... in FJt, 13 f~1111f ;11rJ!Jlll,C. -art'IJrll~l <1f ~he ft'Jlltlr ,if tlie r.1t _l .1,' . ;r; Fi. 12 j lie tun1ur fc1nn,_rl n11.:ta.. ta'i(''i in t!ie lttng Fie, l~. "p111<ll" , ,.IJ ":>ci.nqrn.i ui tlH- tlngli n1et~1:l11... llrdl.lllll; .. .tn:iJJn.ttuti-. nwt:.t"f.1...,1-. in tlll l1111gd( \<!111illlg ,tftl 1 !la llltr.tf<'Jllcir,d 'J: .t :,d '.'. ali 1J1 /f,, .. : J/, .,f ;1 J!tlrr . .ir! 'J\'.r'.1 It'd 2..?tl 11 <. l!lTlTR tio11 in Ll ur .?.-+<; ui tht' ( > rat< u~nl ( h.g,.;. 1.2. U. 1-J. I. J.:y1dcncl' tlnh produced "ho11,; that focal ~,.-,111iiubtic>11< 11i urat11t1111 \rhirh 1,; an alpharadiation emitter may e:-..ert a Cllic"nigernc action npon the ~u1-rrnmd111g ti,..,.;ue,, hut it dnes not di~,Ti!llin:rtt' het\1 een tlw influence of metal tuxicit1 f'1'r sc and radioact1nty in the gc'!ll':'i,; ,,f the,;e lesions. From a critical evaluation of the epiderniologic, clinical. and f'Xj>erirnental nidence a\'ailable. it :-ippear~ that a prolutJgecl inhalation of radioactive g:1<es and or dust rn;1;. elicit iu n1,t11 p11linu11o1ry cancer~ ~52, 12U 1. Jn commenting on the producti<>n ui lung cancer hy atmo<;pheric car- cinogens, an editorial ( La11,-,1. l C/3.?. 1 ( ..i::-: J rernar-ked. "radioactivity of Joachimsthal mines is stated to lie thiny times the tlllerance dose. It is scarcely surprising, therefore. that in the pa,;t more than half the miner,; died of lung cancer." It starnb to reason that this effect on the lungs of workers \\'ill 1irevail \\hen::Yer similar ci.mditions of exposure to radioactive gas('S and dust exi::,t. Comments on He~pirat(Jry lfadioacti\e Cancer. The rapidly gnm ing production and use of raclioacti\e material. and, thereby. conditic>11ed increased potentiality oi inhalation of radio:>.cti\e gases and du:ot for C('rtain occupational groups and pos>ibly. abo. for parts of the general population determine the scope and significance of re~;;iratory cancer hazards which may re'ittlt from such e:-..po~ures. Since the attack rate of lung cancer from this source is w-ry high. according to past experience \\'ith miners of radioactive ores, a competent as'ie,.;-;me!lt of the degree of exposure to radioactive dust. mist, and g-ases by \\'Orker groups and neighborhood population is essential \\'herever radioactive material is produced or handled. The a\'ailahle infrir111ati(1!1 -uppurh the \'iew that the simultaneous inhalation of ,,iliceou~ dust, cau.;;ing the development of a silicosis in individuals mining or prnces,,ing radioactiYe ores, does not represent a condition which fanJrs the production <,f lung cancers. or fundamentally modifies their rnursc once tlwy ha\e bec(Jme esta!Jli~hed (8()). Summary and Conclu"iinn-. The reported eYidence lcan::'S no doubt that there exist an appreciable numlwr of well defined chemical and physical agents which are respon-;ible for the occurrence of cancers of the lung and. other parts of the respiratory tract among members of certain occt1pat1011al groups. The epideniiologic data a\ailahle on these occupa, ti on;,) re-;pirator\' c-ancer-, inrlicak that q111w '1f tlw111 1" ""e'' :t hig-h carcinoge111c potency. Since er!\iro111nental contact \\ith the-,e agPnts also exists for members of other and in part. \'try large ncrupational group-, as well a:- for the p<Jpulation in ge1wral. 1sptcially it.-. urlian rnmprnwm. it can jtbtly !)(' ;i-,1u111ed that -uch <'.'.J><isun, ar111u11t t11r ;lll 1111lettnni1wd 11u111l)('r of re~pir;1torv rane<r- "':rurn11~ :1111rmg th<ni. Tlw \alidit1 11i J :>,\WO:>. \II-.'\ l \I. I I.'\<, l \ ' \ \ I ' ' _)_,,- tlli< ,, ,n,;,i:;iu11 b 'll/!><1 led hy tht' ,t;it;c;ticrl ;rn. I '']:<le 1111<>l1>g1C Lita recordtd 1111 tht: rdatiH irt'<Jllt'lll'Y 11f . ;u!l-.. r <>J th<' :t:11;: ,t111"11~ ,Jiff,nnt c01mtrie'. :-tare,;. region,;, comn1u11iti1~. 1:rl<.tll a:1d n:r:1i :1n:i,, ;1,:i,] brgt occ-tqatwnal gruup,. Th(' pr()lde111 oi 1l,:c1.pati<l11:1' :-v-pir:111r~ ,,t11etT. theref<,rt. j,, not oi ~jl('Culatin' n:ttun hut a I\ 1del_, nc 1 grnn:d lld \\ell rstahl1-he11 reality. \\ hich desern" ~erious l'<l!l;-;i<lc-r:ni<>ll ll"t nly li_1 111c111lier" "i the 1.:ed1,al pi-r1fe,..,io11 and of p11hlic h":,1:h :1.~tnci, ' hut also ]'.\ the rq)resentatin,; of indu,,trial 111anag<:rnu1t :rnd lah1r The generai tYidence as to the recording oi occupaucma) c:111et.T:' ;t,; \\ell a~ the rather recent di,,co\ery oi 111o~t of the re,;11irator_1 ctrcm"gen;; make Jt likel:. that the ,;cope of the industry nlated lung cancn prul>km i, mud1 iarger than indicated h_1 the number ui ca-;es a~ _1 l't rt"\HrtC'd and tiw type~ of carcinugen,; so far recognized. Ep:dcmrolugic data and medic.ii consideratior;s, rnoreoYer. do not support the Yiew that the causation nf lung cancer <:!ild its recent phenomenal rise in frpquenc:- are attribma hle to the action of one single erffironmental factor and it,; recent tntr-ance into the human tn\'ironment, respccti,ely. It ~ecrns rather that varioti.;; factor,; haw Leen responsible for these de\'elopment:-; and ha\t contributed to different degrees to the~e c\ents in different population groups and at various times. An effective future contamment of tlic- en,ironmental resp1rator.1 cancer hazards depends upon the \l'irle:st dissemination (Jf the existing data a,, well a;, on the acquisition of additional information J,) adequate]_;. conducted surveys ~upported by properly integrated experimental \\nrk. Hr.FEKr.:--. r_, I. .\!..!n,__,1:a, 1; "[Jc re llH:tallica" Ba,d. l.'\'.!7. 2 .\1clr1'li!.c:, \\". :.\., narne--, J. ~I., a11d IJeJIL, F. _\, Experit11("lltai ;l\Tyll1un1 J!ll...,(JiJiIJg. iiril. J. l'..rj>t/. l'uthol. 30 .37.1-389 ( 1949) 3. \nit:rilan Cant er S<>c1l'ty Canct:r dC'ath rates f,,r ead1 -:ate !:i the Cnited :"Lttl:'"' by ...ite .\nicriLall Car~cer ~'>CH..ty, 19-i(J .f. \ 111 .. r . . \ } :\ickl'l, in 1Jccnpat1011 and health. lntnnal''J!!al l ,iiF>C Oftice, ( ,, i:c .a. ~uppk111ent (I 938) .\rai,1 . .\I . and .\l un:, K. :-;p~ctrugraphic anaJy,1, <Ji \1,,u.,,, "'' qtk1 1tat1ve anal.',,_ ui mckel 111 tumor !1"11('. 1;1n111 40 .76-79 1 i 'J.f9 1 {, .\rthtein, .\. ~oz1alhygie11i,chc l"nter,uchunge11 u!wr die: Bergleute l!l 1lt:11 ..;" lmetbt:rger Kobaltgruh<'ll, ll1'ht:vmden uher da' \', 1rkn111111ct1 '!a. l!.<.:ll...t'1nten .:--.chneehl'rgc.:r Lungenkreh~e". [f'r1tfi 1!hr ( 1 ff('rr )(111itat 1:... ,<) Bei- i1tft. l I I 'Jl.l 1 7 \llh. _[, J-:1:m', ]{. !J. llc11qwlrnan11, !. 11. and .\J.1r:iai:._ JI ~ I''" lal<' 1. ilt't :-.. of 1uterr1ally dlp1h1tcd rad11Ja<-li\' 111,Ulr1.i 1... J]l n,1 ~l<J ]<;_;2; 1111/i. r;;, 31 ..?..21- .-; \ ll< kt l)tr 1.t111g(11krtl1-- 1r1 tll11:"--t'l111<t'iu1;..!..~r f,r11 11 :~ J,"'<"4) '1 ,{}," /,'1'Jl 2.Z,~ \\ 11 l I !'IR '!. ft.t.uler. E. \\ .. l~LTllf ... krl h" ,,; ">:eutn Frl!.l'hnl .. -..e aui dl'lll (;dnt't dtT 1-(rch..,kra11l.lieitt"l" 1( _\..,,,, ;nd ll. _\ulcr. l'd' >. pp. W-l-l.!" :' Jlll1el. l Lq11i. 1')37. 10. 1~a:idcr, E. \\. lkr l_ti;.~._:.1.,.n:h-.. ;;,}-.. g("\\LrlH.:n1tdi/.i11~"chc-.. J>ruble:n. l't'r- lzand!. d111/ c;t.1 .~/(,;' 571-(t~n~rc"" 32..?-.~32 ( 193'1 ' 11. Hactjcr. _\ :\f 1'n1;;1u11ar~ c.trci11on1a in ci1ron1ate \\~H"ktr..:;. Jlart-.. I l\. II Jr,-/1 Ind. 111": du c1,-. ,0 1,,1n,1i J!cd 2:-!87-30-l; 2 303-.'16 1 J<1_,0). 12 Hai ilJ.rd, l- l I~t1\t-.t. fc;1t~- F, 1u1Htui(1!1. _\ re\ie\\" for 1t)-fO. 13. H:inl<'" .1 \I F"l" '11]11 n:tl !lt"11d11ctiLI~'. of !11a1ig11~1::t tun."I:-- L.\ lh.1:-lLttll1 l.anct'f i.-+63--lri-l (1030',_ l-+. Harne,, J. '.\!., Ile111. F _\. dnr[ ~i""''' H. _\ i11 rahhit<. !Int J. ( ,,,,,-,,. 4 212-222 ( l'l~O; llcr~llium bo:ic ':u-ornata 15. Tkl10u11ek. F. \- rh.1::11i,,e r.h:r f{;,dwa~ ti vita t in C ranpcch<:>rzhaurt vier \on St. Juachirn,tkd f{,,fu11. l'i:.1S1I: Z. 28333-343 (!9271 16. Helwunek. F., and Fon. >.!. Joachrm,tha!er lle1gman11krankheit .'>'trahl.11thcraf'ic. 70 :487--+91' 1) 9-ll I. 17. Beutel, A., and \\'oldrich .. \ Klini;chc und rocntgennlogischc Bwbachtungen nbcr die E11t1nlklun,; d<:,; Jc,achmbthal<:r nr<.>;;chialcarci:iom,;. Z Krchsfnrsch. 34:109-122 (]931). 18. Beyreuther, JL ~luitiplicitat \Cin Carcinumu1 bei einem Fall \'Oil 'ogenanntern "Schneeberger" Lungenkreb, und Tuberkulose. / '1rch07.C''s Arch. l'athol. . lnat. 11. f'hl'siul. 2502.lU-2-U (192-l). 19. Bidstrup. P. L. Carcinu;i.a in lung uf chromate \\orkcrs. !Jrit. J. Ind. Jlcd. 8 :302-305 (1951), 20 Bocmke, F. Das Lungenkarzinom in der _.\,bcshtauhlung<:. Jlcd Jfonatssrhr. 7:77-81 (1953). 21. Bohne, cited by \\'edler, H. \\'. Ashe>tose und Lungenkrehs. ])('Id. wed. IVochsclzr. 69 :575-576 I 19-+3,. 22. Bourne, H. G, and Hmhin. \\'. R. Atmospheric pollution in the vicinity of a chromate !ant. Ind. JJ.-d. ,111d Surq. 19 :568-572 (J9SO). 23. Br,u1d1, :\. Jlericht ubu die im Schneeberger Gehiet auf Veranlas,ung des Reichoau,schus'b fur Kreb,bckampfung durchgduhrten l:ntersuchungen. Z. Krcl>sfursclz. 47108-111 (19.lSi. 24. lln,Jow, L., Hoaglin. L, Ra,mus,en, G, and Abrams, II. K. Occupations and cigarl'ttC "moking a, facu,r, in ltrng cancer. A111. J. l'ubl. f!mith 44 :17118! (195-l). 25. Bre?.ina, E. "Intern;,tiu:;ale l:eber,icht uber Ge\\erkkrankheitcn." Springer, l:krlin, 1929. J. J. 26. Brinkmann Ueher Lungrnkar tin om. fna,,g. Diss. Lc1('::1r1 ( 1924). 27. Calcutt, G. 3:4-Bcnzpyrene a.; an -SH inhibitor. Hrit. J. Can ca 3 :306-310 (1949). 28. Campbell, J. A (l'J-l.Jj. Lullg- twnor;; in mice and man lirit. Jfrd. J. 1 :179-183 29. Caro77i, L. Le can,:er rrr,fr--,iomwl. . frch. rl'.'/,', tr 111,;d 42 XS. 118. l SS (1934 ). 30. Cartier, P. J)i,cu,,iun "ll a,f,e,to'i' canc<:r uf the iu11g. ./.-dz. Incl. !Jy,1 ,1111i Occ11pat101111l .lfrd. 5 2!i2-26.l rt95.l) 31. Cohn,. S. If, Slraw, J<. J..::., and <;ong, J. K. l<.adon inh,tlati<>n 'turli"' in rah . Juli J,,,/ 11111. Olui (J""lf'11tional .\li'd 7-."08-Sl.'i (l'J.;3). ,, I '\ \ I I~ ( J \, \' I "' I \ I" I, l \ t I ~ \ ,, l I I~ ) \_ 11tqH'1, j ~ l l \ r: il nj ,01 ~ .i r 11 .L' t'd. I 'rt,, .Jird ( :1, 1tli1r 187 :,i._ t11r 111 tlie , .tl\"' ,\J/ ,.)t)~ ( }ti,).~) ,,[ , lll..,trLl' 1 ll1".'t''" ,'!,'I Cr.diti"t.t>. 11 ( i. \: 1: ll-.l r.-11 J( L'. 11 ~ ... 1" 1:,11 4 1F ~4~ 'i q; ' 3-l Cnn!1. II _I. ll:t""' II 1 "n i _\,1dn. ,J':" 11;,, \' :: l*l'; i', '.:..: l' l ~ ';\ ,: {_ 1: l \ .l \.' 111 :..'. ( l t l ... \": .. ' ':....'. -+-d1111" : 111~ll1~l .111.tL-...:, t ,11;,,1 /,'i'\,'1n,:i 13 .~.\_:;_3 ..t? ~1(1.::.~ . 1'1 jl<_::jt ,1J "l " .:~ .'." . Cruick,Jia11k. \\'. JI \fL'nl<~ra11\!t11n. }<r.fl. 1)1\i...;, 1 ~: \Ii 11'd 11... tt1ttl !l}!..!JL:1t', 011!.lflt> ,)6. Curctu11, I\.) H.. ~qu,un(ltt ... cell ,,arcino1na ocnHnt'~ i' ;, ... h, .. 11)"~" if :h, 1unf-.' /) 11' J. C,u: ,-,-r 2 2-JC!-253 I 10-1:-: 1 31 ,;~, 3c1. -lO. -+1. -lla . -+2 -+3. 44 lJl':\'ardi. ]. '.!, \',m Ord,trand. II :--. (urtr'. 1,_ II.,,.,,] /1iJJhk1. J h(1 ... i-... ~ln-/L flld. !l.r.(1. a11d ()LtJf,,'iaf111J:"<rl .1!1J 8.1-2-+ }()~3). f)t>nH1tJc .... l\.. Hou ......t.au. L .. ( 1~r1ltJ\., .\! .. and ::---ir( i1-- . . \ puln1unain, .~1'111. f!,;p. (l'arzs) 23111'.?.0-ll'\23 iJ<1-f;-l. .\n1d.nt1i-.t ~ t 1:l'r)lcant.t r I>i\i,ir.n of (Jccupatiunal Health. tfralth uf \\orkl'1, J!I ,-::r.,r1'ate l"''"hc;qg indu;try. !'1t!'1. Jlra!th Ser.-. />11;,1. ( lf'ashinot1111 l :>;.,. 192 :l.11 (j0_'3) Dolrnert, H. R. Eqwrimentclk- l'nter,uclnmgen /'ll!' Fr.;gc .iL, '.'chn('c>IH rga Lungenkrdbe,. 7.. ;..: rcbsforsch 47 :209-239 (19,1(< 1. lJull. R. The cau,e,; of death arnong ga, \I orker' \\ 1r:1 'Jln1al re frrl'ncc tn cancer of the lung. /fril. J. Ind. Jhd. 9:1/;11-185 '19.'2i lJoll, !<_. ~lortahty fron1 lung cancer ctn1c1Pg <'.i...h'-...:11 ... \'.11rk<.r.~. firil J !1ul. J! ed. in pr<:'' Doll, R. an! Hill, :\. IL Strniy oi the aetrnl<>g,- r,f carciw.ma r,f th<: lung. !Int . .\fed. J. 2: 1271-1285 (!932). Druckrey, IL, arnl Schmahl. U. Canccrogenc \\'irku"ge:1 '"" l\.u::'t't(ffFolien 7. .\aturfors(/z. 7b :35.l-.l.5-t (1952 ,I_ !Juhlin, L. I. and \"ane, I~. ]. ;,frtrupolrtan Life I11'ur;1:JCc Co Suney, 19371939. 43 Dunn('r, L. and Hick'. ~! S I:r11nchial carcin,na rn rlu,ty OC'Cllpati<>Jl' in !,,,iler 'cak, and gr<tl!l do:k('r, f;rzt . .!. T1tl1,'YC. 47 :145-El (19.'.lJ -+6 Dutra, F. ]{, Largent, E. J., Ch,,!ak, J, Hubh;<rd. D. '.!., and lfoth, J. L Per,i,tencc ,,f beryllium oxide in lu:1g-; after inhalatirm of dmt .Ir, lz. !11d llyr1. and (Jcrnfialim1a! J!cd. 4:1i~-73 (1951). -+7 I >utra. F. J{, Lari.:ent. E. _I. alld l<nth, J. L 0-tet>g<-iic 'arcon,a after m- halat10,1 oi h:r)llium c>'.i<le .lrch. l'athol. 51 47-1--l/Ci r 1951 ). -ll'. Edi tonal, .\ tmmphenc carcinnguh. !.a11crt ii 30 1 19.'21 -f'J Er,<'nhud, \f. \\'anta. I~ C, ]ltHan. C. ~te;ul:>1a11 f _ T. J Tarr;,, \\' H, and \\'oJf, J:. );f)llUCCUpation:tl !Jcr, Jlio .j, } f11d. ff yo. ,11;r/ (!,-, ll('llfI',11111/ Jfl'd. 31 282-2'1-J I 19-f9J. ,;() Ei,enhud, ~l.. Bcrghout, C. F, am! Stt-adm.rn, L. T Envirr,1m1c-mal '111die< ::~ pl...;.t..., -liJ l !.ilJ1Jf.ilo11t.., u::--i11g hl'r}Jl1111n. J. Ji:tf_ //,,,. flnrf (J1~t11f',1tiiJ11a/ .lied 30 2~ 1-21'5 ( 19-18) .= l. EugiT, 1.dJ;1karl1llllr un1I l!t1!11lll.dhrll, .. !111/ur1 /J11. f1'l/-t1111(i2.~1 ~.? Evan .. , 1~. I), f.J11ant1t;11J\t a .. Jll'l'h nf r.tdiattiJll , ;1r1 ::1()gt:,1~i-., 111 l1un1ari-- irta ri/111 f11f,r11 l 1!//f/1[ ( dJ:1 l//I// 6.122(J-12-~7 ~ 1r};:!) I_ 11e ... er, L F ~u!!H a']Jl', ( .. oi tlw < lH 1111..,tr~ ,u.d !, 111.-L :n:~!;_\ 11f 1 )r,J:, .._f( rr1; ''""" 9 /J11./J1, 1}'1'-11 2.10 \\. C l!l"ll'ER 5-1 F1e,t>r, I. F. a: ! crccch. I! The i..'t.1r1jugatin11 oi ,u11inoac1d:-. \\'ith hJ- 1::1 11 ae ... (1f ~hz._ ~--- 1 r,:~t'~t.: ..i:hl 1.2 hl'f17a:1t\1rac1..11e ~l'ril'" J. 61 ;3,,02-351)(> ! l <;,;() I !u1 (-h1'1n .\(,, 55 Fulton. J. ~ C;Lr..:1no1na ,1f !un~ P'c>C. l{o_r. S11( .1/c'd. 42i75-782 ( ]<J.f<)) 56 Gafafrr, \\- :\!.. .::.,l :-:itc:na'"' H. cancer atnL11g nL1 J)i,ahling 111orh1d1ty and mort,tl1ty frnm Ii"..\'.) ie cn1pk)\ce-.. uf dll oil 55.L'l7-L'..?> ( J0-!(11 re-tining con1pany. J>u11!. If t'a!t/1 l\<~pts 57 Cardner. !.. l' l'kalth in indt1,try. :\f,cting lndti-tn ,; H~c:1e1:c- Bulleti'l Xo 8, Tran,ac-tions 11th .-\1mu,il 5R. (,j;Jc,pie, '.If Fcn1ndati..m of .\nwrica. lCl-16, pp 89-9-1 I JCl-!71 Pnn;ary llltratilurat'IC grcJ\\ th;;. Glasuocc' .l!cd. J. 59. Gloyne. S. k S iuamnti:; cell 1ar1inoma 0i lung 118 26 ( 1932 1 occurring in ashe,;to'i' iJu'uah,c!rJde,eto1s7i" S-i1f,0,,J '11083:~1U).ll.-l'\l.llca1;e193o6i1oat cdl carcinorna of the lung r~:curring 60. Goldhlatt, ~J. \\" and \\.dg,i;di, \ . .-'\.. .\,pech of indu,trial medicine and hygiene in German cherrncal factories. Relea,cd ior Puh:ication 1 19-181. r. LO. S. F111al Rcpt. 1501. Item 24. 61 (~renfrll, cited by Carozzi. L. 05 (1934). Le cancer profcs<ionnel. Le 111/d. du tru1. 6 l, 62. Gporougnadns, \\C'i.th Hp..rotaell<inl '. OpTpoenhheeimpeurb,lisHhed. Interaction of Crill and Cr\"! com- 63. Gross. E., and ..\!wens. \\'. Ltmgenkrebs c!urch .\rbeit in Chromat hersteJlei;- 6-1. den Betrieben. Ber. Jnt,nz. Gsell, 0. P,ronchialkreb, K 011gr. L'nfa/lmcd. 1938, 2 :%6-982 (1939). (1951). und Tabak. S'clmci:::. med. Tl'orhschr. 81 .662-6'58 6.' Haddow, A. The chemical and geneti, rnechani,m< of carcinogene;is. 111 "The Physiopatholog-y ni Cannr" IF. pp -1-11-551. Paul B. lfrdJa, Homburg<T and \\'. H. Fi,funan. eds. I. 66. :\('\\. Yurk, 1953 Haerting, F. H., a:1d Hes;;e, \V .. Der Lungenkreb>. die Be Schneeberger Grubell, 1icrtcl_ialzrssclzr. y,richt/ [X S.J 30:102-132, 296-309 ll879). rgkrankheit in den .lied. 11. <if!cut/. Sa111tai.1''. 67. Hcealml mdievtit,.ioFn.. SArchIm. elr'aptrleiotal.tir8,n:57,,5f-5m94alig(1n9a2n9t ).growth ha,ed on chemistry c,f 68. Hardy, H. L 524 (1952). Occupational medicine. .Yea Enqlaiul .l!ed. .!. 247 .473-483, 515- 69. Harrison, C. V., cited by Smith. \\'. E Survey <>f current British and European >t11d1c, of occupational turnr'r prohJcrn, cupati,1nal .lfca. 5 2-12-2'13 ( l'J52J. .lrrh. Ind. fly!f. and Oc- 70. Hf'heanrd11ry1a, coJl.. A6.:,20I1~-o2,3e-.1 F(.19L5.1. ).and \\.alpole. :\. L. Cytotoxic agents Hrzt . .! 71. Hendry, J. :\., Homer. h'.. F, and Ru,e, F. L, and \\'al pole, .-\. L. Cytotn>..ic agent,, Hnt. f. Ph,1rnwcol. 6 235-255, 357-410 (1951 ). 72 Hfot<rdnryC, mS.veAr,ity"CaPnrcPe'r' ofLothnedoSnc. ruJtCuJ.mlfi in Helation to Oct'upation," p. l 12. Ox- 73. Hcieirebchbawo,i Pp.ilSe., rRadilieaty1,uEn . FJ.<. aadn10d/01S1tyapl4e9to3n4,9G-3.5E9 . ( 1P9l4t7Jt)o.mum project. Riolngit' i4 Hill, .\. H.. a11d F<rning, E f.. Studic, in inridencc of cancer in factnn handlmg 111org<inic '1111f!()llI1d, ol ar,c:nw Ifni J Ind. 1!,d 5 !-IS ( 19-1~) 7S Dlu1ntra,F F/.'aIthC,,i;m2d6 '1..'1<7tr-g20n2t. i E195(j).) O,t"'''arcrm1,1 1nduct'ri by beryllimn oxld\' I' .\ I ! R< I.\ \I E \ I \I . I I \ <, t I .\ t l H /!"' Htf\'.r,y1gtlliannndl. i~ndLuBcl,'d OC"tncl~'1r.,. archt'.>. Ill~.it.a.u1(_d,U1H(o1~rHI.,\.,,',.,l ,;r,L:. 10f;trT1}.2ltlLir1,1,~~_t;n I.uIHt)l:.og) r(l\\1 II IInlJt:"h, lL I!. and .\ngn-..t. \ CanJnqn;a ;i,Jw,to'h . !n1 / /'t11/i,,/. 18 123-135 1 J<i-ll .1 ........ ,h1.i.tiu11 \\1th pulnllHld ;-:..: lldniliurglr. F Th( l'P lilt. idence (i prinictl} ~~,~;-1,. :: nr:.t ..~ <1c.. ltHl,\-! .... ;u pulmonary a,he<to'i'. . 1111 /. l'ath,r/. 19:i"ii-::-'1/ , 19-1,,1. j'(J. H11ph:i11', R. a11<\ Studdiiur \, .\l T dt'rill,ltn-..i-., in :\(~ro .\lultiple ep:t;1c>liorna~ and pigmt'ntar ("'ti hoy. . lri'h f>,T111ato! 11 Hnpkllh, S. J., and \\.onn:tll. .-\. l'h..nyJ-i,._ -..:., .."; 111 s 29 ~!J~~-L?l 1 l').~.f J. their imrnunologira! propert1e<. f)i11, hnn ...-, .rn:!te prt>tcrn ,'ni\-:1ti1 "' ,rn T. 28 .?2"-236 I lli,q) Kl H, rning. R. Betrac!Jtm1g:n zur Frage /.. A'rcfis_f,1r.1'<''1 47 :21'1-..?87 ( 1938). de' Jierui,krcb'c' der .\,he,t.irhcite1 K? HTm!J1pmc11a-.' \\"S.plri.ng f"iOeltd'<, 'llIpIIa..tio1n'>a-l12.Tum"r' .wd \ilJ<,i ll1taL' ... Jl S"r' Ch.trk' ( "'0' Hueper, /',1tliol. ,\.. C. Polyvinyl 31.11-2-1 (19-11 ). alcohul athaomato,z< 111 the aricrie< oi ring<.. lrh 8-1. Hueper, \\'. C. Significance 17 218-242 I 1934). of ,ulfhydryl a< a ~Trr11 th fact<>r. .-lr,h f'atlwl !rs 85. Hmper, ,,., C. Xich:cl cancer, in rat- Tna( 1/i.fi ( 1932). /!1,1/ '""' .lied 10 .167- 86 Huqwr. \\'. C Occupational and cnvironnwrtal ;iulrn()nary cancen with ~ mimeciaoln rePfneereunmcoecotoniop,ni,e;u, m1o9c5o2n.iosJin<. prPer,o;;c. eedings of the 7th Saranac Sympo'c/. H5 u:1e5p7e-r1,65\\"(.19C-+. 8).Clinical a<pects of occupational c;..:Jcer. (Jr,11ratio11al Jf,d KS. Hucper. \\'. C., Allen, .-\., Rthsell, .\!., \\'ood11ard. <;. and Pl;<tt. .'.\f. Studie< ~9 "" gro1\th factors in embryo extract' Hw:pC'r. \\'. C., Zuefte, ]. H., .-1111 . .!. Ca11ur 17:74-105 (1933!. uranium cancers in rats. Lmk, :\. :\I., and John;;on, .'.\!. G. ExperimC'ntal J. .\'at/. Ca11ar Inst 13 .291-305 I 1952 ). CJO. H"nuepcchrr,om\Viu. mC,pr(o;treoignanc, umC.plHcx..e,a. ndTo}ohhme opllu,bl:t\,!!-.-eGd. In1mw1ochernical ,tudie, 91. Huguc-11iIJ. E, Fauvet, ].. and nourdm, ]. I<i'.e e\t"ntuel de< n,;hulJ,ation' de certaines huiles indu,trielles flu//. 111/111. soc. 111rd. lzuf'. dan< l'etiologie due cancer hrnnchopulmunaire. 92. lmpn,cia. S. Paris 65:1020-1022 (1 1!491. nronchogenic carcinoma and chrr1m f'/z_\'S 22 347-355 (1952). ate-; J Am. coll. Cltnt '13 Jc,a,ercJibnaocmhear., K..11.11]. .,J .Kl.lafurd'.. H15., :7a2n1d-7H32ard(y1,95I3l1.. L. _.\, bc-ir"i' and hronchr,g('nic 9-1. Kemahalnaaut.ionC.. lE'.-xrph<a'rnimdle.11dt,e1l1l1c EGrczsc. ugPuantlgzol.\01312:3L7u9ng-3-1-1\I5tum(rJ1r1<J.5:1(J1J. <lurch Radiun1- 95. Kr;a1w:rna:hraattnar,[TK:l<. ;-f'Vahernikeartiodni.e bc,e',1r1umftic3h0e .3E-1n1-t3-4te4hu1nlg'1.\dIJh, Ll.u{n'hgeernkr!r1eel"e' bei drr 1H1 ernl..oeir1geru(f,r1n1mc1312 L.1u67n-g.1e1-1171kn( IbC,Je3l{)lwi <;1Hrat<Jr-l;a, .\rfw1t('rIJ in dfe..!nt'\\ e"rtlialhiclh- 1!1i. f,;<1pJ;l\\ ay, X. ~I.. and K l'lllla \\ ay, E L. .'itu ~, ,f inczdenre ,,f <:ilJ<Lr oi laryn-.. and lung . .!. //yr; 36 zy,.2r,7 11 11.l!,1 ;-;t.,,;_, ,,f tlw ;," 1r!'"1Jc1 ,,f, ,llJ<'l'r ,,f tlic ltu11-r and lar_\ll.\. i:nt J (i1J11, r 5 l.'i.l-l '.~ l'J:il 1 J fJ7. 1--.:ltnqwrt'r, F". \\", ~fartui, ,\ P, ;nid \".n1 1\qwr l~tr.)l1111n1 !').t~rell1J;1 ~r: ;:t:1l'd.lh, ./r,/1 Ind //\'/ iJJt~i r1,(u/l11/111nal 1/,1i 4 2Sl-2_;r, 1(J~1 l 1 . , '_) , ) _) \ \ , " l!l'l:l'l"I~ ()~ 1\.(1lJ...,ch, F. l_u:.~t'lt:.. :th' und Tlend. ~ /,fd l ~iuJ lllti nz :1mtra Ca1l(nn11 3 ..?~J 1JOJ;~~ 99. Kotin, P, F.Lik. H. ;_ :\fader, P, and Thom;b, :\!. :\rom:nic l1ydn1carhrn1'. I. Pre .. ence 1:1 the ~/)'. ~\~1gelc-. at1nu... p11cre and the r1rci11o~cnicity of atm ...,plwric e:-.tr;,Lt, .'.1.h [,:d !lyo .111d c)ff11f11tic>11al 1/,d 9 IS3-163 (J<J,;4)_ !Oil Kotill, P .. Fal:.C. f !. I. and Thn'lla' .\!. _-\nmatic hydnKarbcm,_ I!. Prc,ence in the particn!.ltc' pJia,e of g.t,cl!llc engine e~hau,t'i am] the c.ininngenicity of e:-.hau't extract, _Ir.-:: f,,,,. !!_\',<!. a,.d Ou11patio11a{ J!cd. 9.164-177 l!954). 101. J(uroda. S. ()ci,:u11:iti<..);1;d p11ltJl<):l.1r~ cancer of ~enl'rator Q,i..:;, "Prke-r.;; !11rl JJ.-d. 6 :304-306 i ]0371. JO la. 102. Kuroda, S.. and K,, \\ ahata. K. l"eb<:r die ge\\ erbllchc Enste~rnng de-; Lungenkrcb<t,; bi:i (;e::eratorga,arheitern. 7-. J{rchsforsch. 45 36-39 ( 1936). Lancbteiner, K. "L>ie ~pez1titat rler 'erologi>chen Reakticnen." J. ]. ::;pri11ger, HC'rli11, J93J. 103. Lange. K. Kreh,erkranku11grn und ge,>logi,che \'crhaltni,;5e im Erzgebirge. 7-. Krchsfors,h. 42 :,~t'i-310 ( 1935). 104. Letterer, E. l'nta,;uchungen einer Chrom-Silikoselunge. Arch. Gc.-cr/icf'afhol. Ce;,""rbcl:y,1i,-1;<" 9.496-.'0S (1938-1939). 105. Lindemann. l.."tber Kreb,erkrankungen der Bergarbl'iter. Tl.-111. med. Frcssc 20:3-6 (1916). 106. Lin7bach, A. ]., and \\"edler, H. \\-. Occu1Jational cancer among a,!Jestos workers. VirchtJs .!rch. tathol. Ai;at. 11. Pliysiol 307 :387-409 ( 1941). 107. Lisco, H., and Finkel. ~L P. Obsenations on hmg pathology following inhalation of radioactive cerium. Fcderatio11 Proc. 8 :360-361 ( 1949). 108. Loiseleur, L. Les trar: ;porteurs et Jes fonctions-ant1corps corrcspon<lant aux molecuk5 minerales. _-J111z. i11st. l'astc11r 84 :333-363 ( 1933). 109. Lpkeu, A. C. Lungerkarcinom Hos X1kkelarbeidere Tidssl.-r .Yorske LacgcfvrcJ1. 70 :376-378 (1950). llO. Lorenz, E. l<:adioacti,ity and lung cancer; a critical review of lung cancer i(n19-t1h4e) _miner' of Schrweberg and Joachi1mthal. J. Natl. Ca11crr fost. 5 :l-15 llOa. 111. 112. p, .t Lorenz, E., Heston, \\'. E., Deringer, ~L K., and Eschenbrenner, A. B. Increase in incidence of lung tumors in strain-A mice following long continued irradiation with gamma rays. J. Xatl. Ca11ar Inst_ 6 :349-373 (1946). Lo\\'y, ]. Ueber die Joachimsthale Bergkrankheit. Jled. Kli11. (M1111ich) 25 :141 (1929). lJ<:r J:ronch1alkrdh aJ, Beruf,krankhcit. .!eta l:11io I11tcm. co11tm Ca11cru111 3:182-187 (1938). Ludewig, P., and Lore:iser, E. Cntenuc-hung der Gruhenluft in den Schneeb(1e9rg2e4r). Gruben aui den Gehalt an Ra<liumemanation. Strahf<11tlrcrapic -128-435 Lull, L, and \\'allach, A. ~Iontana State Health Department. Unpubli~hed data. 114. Ln1ch K. and rar>11,,r_ \V. }.f. .ls!.:"stu.1i.1 v;. CJ.,,1 14:1'/4-i\9u (19415). ] 15. Lynch, K .. and Smith, \V. A. Carcinoma of lung in ashesto-silicmi,. Am. J. Cmzcrr 24 :56-63 (] y,;5). Pulmonary asbe,tosis : A report of bronchial carcinoma and epith<:lial metap!a,ia Am. J. Canar 36567-573 (1939). 116. :\lachle, \V., and r;rcu<;nu,, F. Cancer of the rL,piratory syskrn in the l.J. S chroma!<: prJ<luc:ng indmtry. Puhl. Jlealtlz ffr,ots. 63:1114-1127 (1948). "\ \ ! I\ () '\ \I J '\ ! \I. l 1 '\ I ' \ ' ,, l l l~ ' ) _,) 117. :\L{i .. in. J ; (." l dlH,Tf..., i ){ I ~ r(""" j( ) J ] Jl 1,: j lt ' "' I" II:'. .\I anctt,n, 1 F. L~n11 1 1i " .. iwd iLtLl 1t'\ I 14 .:.\.j I J<l.).j I 110. 12\1 121. l.!2. 123 124 123 .\lancu,o. T. h;v,trd"' ir1 .l )..!artLotrl. 11. eel). 7th 1..'d. F and fl tit'!'< r. \ \. l (),,t:: chrrnnatc 1L111: fid . .lf,1i JI, ~ H.1dit1111 11(1\,1f'lJill!. z,r .. il ,~ p ,;~2-.:::.k/ ]li-l/ J-~:t: l'<1"' ...1. r .... nl '-''11/ 20 .;:.~- . ~r1,~ ,\ fi \~t\li~:r:\.' 1 1t1lt r 11q~1) i l\. I hl'.dtl t'1:cil ~fayer, R. L. Av1rn,ttic ;;mirw< anrl :uo-rl_\ < 111 a!k:~y "'I c.1:1\cr. Inst lnlcsf. /),T11:ilf11f 10 3K(J-_)t)fi ( ]tJ-J-K). \le Laughlin . ..\. l. (;, hdti-tn.ll worker'. Great Britain F,1rtory Sen ice. l T \I S.O, T.nnrlnn, 1950 lung di'"-<' <''. :r. i:1 ;p1d Dept .. '.! 1". '"'Y <>i 1 :1hc1ir ,1c-d f"tmdr: a11d :\;1tic)n,11 :\I cre\\'ether. E. H. _-\nnual Hepc>rt Chief Jn,; ...-. t.ir pf F.t:toric< f,,,. the Year ]</47. PI'. /1/-~J :\ferL'\ITlhcr. E. j{ 19.\8. pp. 0_?.93 \IHl!lal Jfrnprt Chid f11,; .ctor of Fact()ric' ft1r the ~ear ~lilkr. E C. Stulic, on the ionnation of pr..:<::1 hnuncl rkri1:itiH, of .'l.4-hcn"pyrcnc in the epidermal fraction of mouse ,k:-1 Ca11.-.-r Rc'l'rt1rri, ll-lil0-10-< ( 1951). 12h :\!ill<:r, E. C .. awl :\filler. J \. The pre,cncc ;,,1d '1g!liiicancl' ,,f hnund ami110azo dye, in the llnrs of rat> fc:I p-d1meth) Ian; 1oaznhc11,cne. Lan,-,.,. !<t.l'<"arth 7 :468-480 ( 1947 ). 12i. \!organ, (;, Pcr,:onal conmrnnication 12K. :\fueller, F. H. Tahakmissb~auch und Lur:i!cncarcin.,m. 49:57-85 (1939), Z. Krebsfnrscfz. 129. Xa<h. P. J->..perimcntal pro:luction of rnaligna:-:t tumor< Ly kryllirnn. J_ancrt l :.;J9 (J95(J I 130 Lclten:r, E., :\eiclhanlt. K" and Klett. H. Chrc,matlmH?tnkrd" und Chromat;,taublung-e. Arth. Grwcrhcf'alhnl. Gri,rr/Jch_rn:c11c 12 :.123-.161 (1944). 131- X eitzel, E. Berufs,d1adigung-e11 <lurch rarli,-,;,~:ti,e Sub;tan1.en :\ rbeihmerl. H ('ft I. FJ.F. 132. :'\('ubaucr. 0. :\r,crncal cancc-r: A re\ic\\'. Rrit. J. Cancer 1:192-2-14 (1947). 133. Newman, D. A Carci1wrna of the left infuior turl1inatecl body am! perforated na,al <;cptum in the per,on of a worher ir1 chrnate 1';rn1ent'. G/asyo Jlcd. J. 33 '469 (1890). 13-l. :\"nrdmann, \f. J,tl/ll!l'na,J1l',\<"e trnd J,unf!en'.:rcl,,_ Rh I11t~rnat Ko11gr f. l'nfallrnc<! u n"nrf,krankh. \'ol. 2, p 983J1<:;.; Ce<>rg Thiemec. T.C'ipzig-, 1039. Occnpatio'1al ca'rcer 111 a'hc-to<; \\orLcT< 7- f:rihdor,,ii. 47 2"K-29R (JCJ.<8). ] 1 ~ Oppu1liei111('r. I! '.' .. (lppcnheimer, F T .. S1,-1'. \. P. an<! Dani-Iid-ky, I. :\I alignallt tumor' n''nlting from emlwrldi!1g p!a-tic' i11 rod< ll(,, 118:305-306 (19531. Sci<'Jrrc ::c.'. 136. Peller, S. "Cancer in :\fan," pp. 11'2-187. frternati"r:al l'ni\'er,ities Pri" "'_ip.;I k, l 1J,':'..2 l-'"" 137 l'"rry, I\ . J:<J 1.\'ler, R. <;. f~nrL('ll, 11. '.'If. Drue' If \ and Sd1ilii11g, f.t <.; F ~tuc!Jl'-., in tlie i11cidt11cv ui c;n1(c r in a i.!1 tJr_. iiaJJrll.- in'Jr~;111i~ < t>!IJJ111llJ1d'l <Ji :tr"nic nr1/ .I !111/ '1[,d 5:1-l:i (]'1-J:-;, Pircl1an, .\. a11d ~il...1. l f. ( 'a11iir of tin ~i::.:: 11 1 _lo.u l1111ht.11 J. npiJrt t1i (a .. 1-., (,b-.,(r\td 111 1 1l 1J 3fl 722 ( ]fJ.\2) f'' JJL\;1 r-, <)f f;~( :1in1.iv Ill J ( <l>I ,r 16 11-:J . w '.'!3..J. \'. 11\"l l'EI{ 139. P,ittcr, V. I~. of p-d lnlnhmon ni -uliliydryl-cuntainmg in1eth} l.un111oa?nht11?.('r,c:.' J.fll. Prub>t, h'.. Di< l lam Cd,11(1 !~t',~.ir,!: ('!l!YTll<'' hy <plit 2 :("\~~-6').) ( j()..t2 I !'rudu<'t< (1927). igkeit de' l .ungenharLinonK 7-. !\ r,-!>sfor.1"ch 25 :-Ul--1~3 1-11. H49ajt3"1w5,kIy\,ClHJ<. L]<ni..ej(r))idit uher .\.c :'drneehcrger l'ntersuchung<'TL /. f\, ,:,_,.r r.1(/z 1-12. Rzeajueg1u1-nsgkyd. ur1c3h.. J~<c:ihnraatnu1bu.ng .\\"(.Hi ,r!n\addnnKnaehlau, (;. Experirnentclle Ce,,hwul,ter- 171 ( 19-13). 111anation .\"at11rtl't~!}-,'JZS(/1 11ft,n 31 li0- 143 f{i;,el, cited hy Thiele. -\ clu chcmi,c p ... s~ 1 i:1cd.JC1gc:1 Lun!'enkr,rnkhr J J. hen lm\u,tne. \lc-rhhlJtter Springer, Berlm. 1930 uber herntlidie 1t, in F;ihrikarztt" Erkrankungen . .'rd ed. J-1-l. Ho<l1H'Y, (;, alld Fell, X. J. nnmologic f!15tamine-protein complexe'; lu11111111ol. in H> tigations uf 47 :2.51-259 ( 1943 J. i cta-1 5-imidazolyl ethyl sr1ithe<is d!lU 1mcarbamido-pr11tei n. .I. 14.'. J{oesch, H. c/i llrei ver,chiedt:'le Cafl'inome hei einem 146. m('S .!rd1. patliol. RonJoni, P., an<l B ,-foal. 11. I'h1s1ol. 245:1-8 (1923). Paraflinarbciter. I ir- on SH-activate<! arbieri, G. P. The action enzymes. En::y111,>ln,r;ia of some carcinogenic com1v11mds 14i. Ros>, P. Occupational 374 (19-18) skin lesio11' due 14 :10-14 \ 1950). to pitch and tar. Hrit. 148. Hostoski, 0., Saupe, E., J!cd .1. 2 :.169- leute in Sclmeeberg in and Schm(;rl, G. SacJ1,t:n. Z. Krch Die Bt'rgkrankheit der E.,lwrg- 149. H23ou:1s8se1a1u-1, 81L4. (Q19u~e7l)q.ues Considfrations _,ur sfi'oarmscinha. nt2o3s:e..)60S-h31814. (d1'h9o2f>6.) (!'ans) 150. l{msell, B. F., and Klaber, R. 128 (1938). Pro.- l<n)'. Soc. JJ,d. 38 Xo. 3, 151. Sante, L. R. The fate of Sc<' Jlcrm. ship to the denlopment oil l'articlc;; in of brc,nchiog the lung and their IJ<w;ihle relation- 62 :788-797 ( 1949). emc carcinoma. A111. J. Roc11f11cnol. 152 Saupe, E. an den A Gew~rbehygieni,che und klt111sch-roe11tgenologi,< Sachsen. rbeitern der A.rsenikhutte Fortscltr. (;eb der staatlichen 'he Unter:'uchungen Huttenwerke bei Freihe 153. Schinz, ll. R., and iefp Ro11tgo1strahlc11 Uehlinger, E. 60163 (1939). rg in 437 (1942). Der ~fetallkrt'h;,. Z. Krcbsfnrsch. 52 -12.i- 154. Schmorl, G. tioual Pathological study of Sch11eeherg lung c Bri>tol.Cancer Conference, Lornbn. 1928. p. 272. ancer. lfrport l merna- Jolin \\"right a1H! :-;,,II,, 55 Kahlau, G. Experirnentelle Erze-ug-u l.td, 56. emanation. Klin. ft' oclnchr. ng wm 27 :551 ( 1949) Lu11gentumore11 durch lhlium- Sac' hreetiko,loRg.i.c Bfaacker, L. A., Ballard, G. P., and Do!goff, S. Tob 57' Srntt, A. tor in disea>e: Cancer. <kn1pat icrn ca1v-r Ca11ccr l<crcarc/1 10 :49-SaRrmI 1"91~1(1okI mg ml mdustry. oi r,arafl;z, Brit. lfcd. J. ii ll<J~-ll09 lid oil WtJrken of Scotland -hale ;SqK_ S(e1y9f2a4r)t.h, C. Lung cancer~ in L<'l{J.<ig. (/J1r9r2tf2.1.med. Tl"o1hst'hr 50 14'J:C-l-l9<1 S"'i'k~l',ia If3.2.6U0e9!-Jfe,1r3deIn1?L31unJ.g(nkreb, rler bergkute in Jr1achinhthal Ts< ii<, :,,,,/o- E.\\Jl{()'.\\IJ''.\r\L J,t',\c, L"\'.\IJ:R .!3.~ j()ll jl_; 1. 111.? 16.' '1~-- 1 1b, }1 _\ I n1 nulll' ..,,trt'L>I ',l pn>dth'crl t'\.]lt:rimcnt:ti 1 /Ji.'1'111 ~ncgirefF. L ~ o111fro ( 11no1un 7 171-172 ~, _.nd t 1''::;0). y :n - ,! l ,I I" t J, 1,1 Lorllhdrd. () ~l " d1.d (!, <i!f'<I1i<'Jl<lf .\/,d 4 l'lO . .?(I~ .\r . . u111' .i:d tdil1.'t'~- h.! I J C:.tcplkll', (;. J/,,d ( )<J,;j, l'r,-,., ,url , 1r, 187 :.?lo-.?11' r!1. J. :StocUba, Vie J oacliirrn,thaler Hc.:deut1mg der I ]'13,)). l .uitra<lioakriv1tJ1 hci der 1 : .. 1199-120() und il'i.l.\). '."ch1wrhcrgL"r Ikrgkra11kheit TJ.-ut ?.t:1n111 g dn 11 .-J. i; "-i: ~l l: ; 59 104 ~tock'. P. medical 1-~egional a.ncl local d1ffen 'lCe:-i 1n rancl'r dea and popul;ition suliiect>, Xu 1. p. -lli. th :-:lt(' .:'turlu:..;; i111 General Hq.;;,, 1t'i. Lo1 HHr.i.t\.l .Sl..OC. 11J1cJ..<fir. 6E:9n9d-c1m11iolIo1g4y.'.?uf cancer of the lun.l( in Eng1anri< ~nd \Y1cal"k11, 163 ::;tokl!lger. H. E .. ::;1wague. (,_ bery I F, ancl llall. R \\". . J tifi. llium _/rd1. Ind. llyp Stull. IL B;is<. R, and O,-mf'alw11a1 \cute inhalat':1 tuxicit~ .1/cd. 1:379-.W7 (lG:'-0). ,.f genic rarcinu:na . .~rcahn.dJ1.11\,nng1r1i1s/ t,_lf:,\d.. :\. _.\,be,tnsis as,ociatec'. \':i~ 1 bro11chn- 167. Southam, .-\. H. pp. 831-834, 19.~l. .\Jule spinrier>' cancer. ''RP 168. Conference," London, 1928. p. 2110. Sultzer, .\I., port on 111ternatiY~al John \\.right and Som, Ltcl, Cancer and Hursh, ] B. radon. .-lrch. Ind. Jlyy. and Polouium in the urilie of mirnr,niCi',-tlo'"l'ed t 169 Tahershaw, J. R. Report Occ11patio11al Jfcd. 9:89-100 on industria (19;;4 ). n liO. Germany. Te!eky, L .frch. !nd. H.wJ. and l hygiene Ocrnf'alional .if ed. in the 1\c;tern 3 :2<Jg-313 zone ui 171 Tourame, Occupational cancer of the lung. A., and Bour J. (1931). Ind. llyr1. 19 :i8-2:'- ( 1937) . H. franc 20 283-292 ( 1939). Les cancers par huile,; de grais<agc Rh mid. 172. Tk<recbhseel.nitzS,tr1H1./i!{'lB1/elrmcrearfk'iucng53en.26z9ur ( :1\9et3w5l)o. ;.:ie ckr St. Joach1mtha.l:r Lu11ge11- 173. Tinurnraetrs,. F!.. CX.atlS. arCcaonmcear a1t'1s,il.tcs2 :8o1f-P.sJubcuta11eou,Jr 1111plantt-d h;,.-el1k di,k' 174. Turner, H . .\[., and (jrace. IL G. male> (19-11 ). All ime>tigation of in certain Sbeflield trade<;. J. JJyg. 36 :90 cancer mort<.lity among ( 1938). 175. lA'hnlaigt., 11~.f.f>hty:seibo!e.r 23d0ell:76S-9c8hne(1e9b2e1rg)e. r Lungenkreb;. T'irc/1oz"s .-Jrch. f'al/101. 176. \'cr,!uy<, J. J. Cancer and occupation 3:161-185 (19-19). 111 the '.\l'thcrland, JJri1. J Conc,r 177. Vu!lrnann. J. depot. Tierexpl'rimente mi t intrao,,aerem .\n( 178. :-,'clt<l't'l::. Vorwald, :\. J. Z. P aflur111. l'athr,f. 11. 1-iailtcnol. l IJ-, Chr'l!ll - u .d K u1Jalt-l-10--1-13 ( 1';3i-'-19-l ulmonary ca11cer in experimental expu,urc- to 01. L><T) ll iwn. li9 \VPraolcl,eeLd.i,nga>nd S~efnag-natth, ~Sf.aranEaffcecStsymopf matioumm. In prns. _l nly Fl.'J, i,. >. ic rarliat1n11 on P"l)rnU, "P!a,un." i81J \IV1a9l5ie2r),. R E. The !Jen.<pyrrn<' cu11te11t ,,f t"""" air. lint J C '" <r 6 8-21 !Kl \3V5el'>!2e9r-, 7~L1 . (F1.937E) xtanal cau'c' uf dermatJti, . . Jn It /1,r111arol anrf )1/i.i/,,/. 11'2. \\'edkr, H \\". _,7{, 119-<.11. A,]Jl',to"' urni l.llllf!<'Tlkrth' !Joi! 111<d 11 ,,,ii,,-,.,,. 69 ~7:0- ' . ..?3< \\'. ,. 111 T!'l I~ IK3 18~. ]."\~, !XI>. 11'7. 18X. 1X9. 190. --+". \l\''ec1H"lC.iPli.~eSn ., S. m!r.,'lt:h. , I1n1d, F/.,/\'a1/1d ,p~-;t,/it'.r J.T1 .. t\d\/'1,.i;,1(1]/u<_',1t,'tdf,.,,. 5a53'll:'iP-S<.'l.lf<i '<{I l<iJ1S.1.?dJthtrial \\'d1, .\. \\'clll're Jktrachtullgcll u)l\'l' dcII ner\ll>kt'tlb dcr .\.]\c,tar1 t'll<'L . f,"f: t;~1.._trl 1 trdt'11l c( il'tr/111:_, 011-ili' 11 _;3(,_:;_::;o ( It..)-f..?). \\ <)01~ F. l I l"n1i...u,d cl-.,e of car.._11~oni2 pf hdth lurig:::; a~ ...n'-1atcd \\1th 1ip1lid p!lt:ll!l1Jllia ;,a(!111/()!l.\' 40 :103-ICJ.; ! }(;-f3 ' Shapiro, J. H. .\11 l'\'alnatio11 oi the pulmcmary Ltdi.llit>n dthagc from rarlu11 and 11< <laughter r;r<>clucts. l'.R.-.:?01\ .\wmic Energ} Project \\'-7401-cng p. 1-ll. The l'ninr>lt\' oi Enchctcr. F!Sl. \\_y 11,:ex, J~. L., ;u1d C1rah.u11, 1:.. J. 1 \ 1!iacco :-.111okn1g as a P''""'1hle t"ttol(1~:c facttff in bro11chiogt:1ic carcinom:t J, .1111'J,d..-!ss''' 143:3.:?0-336 (19.'0). Et1u:ug1c factt>r.., in brn11chiu.f2c:1ic carcinutna \\ ith special reference to indu,tnal expo-ure' . . lr11r. Ind. lf_\'!1- 011d (),-01f't1fi,Ji1.1! Jfrd. 4:221-23.S (J9.:;J). \\-yer>, JI. _\sbetsi< ]',.,,/ ,,r,1 i .'![,-./ J 25 li31-ti37 (1950). Zid, R. Zur Fr.tge dt I .ungc11l;nhl' l>ei den lkrgkuten in Joachim,thal. Jf,d. J\li11, (Jfuuich) 31 :1535 (193.'). Zollingl'r, IL 0 Experimc::1telle Erzeugung maligner Xierenkapscltu1111Jren bei der lfatte r!urc11 Drud. rei l ( PJa, tic-Kap;eln). !: ,- lwci~:. Z. Putlw.'. 11. l:ia!daiol. 15 .666-671 ( 1952). Problems Arising From a Study of Tumor Host Relations !{. \\'. ]:].<;<; /1i fdrt11!1'nl \1f -~f{,fit"ur' Ni'\\\Irl h, /,'[~ l'r,1/.l df u(',\f1'IJI ( ld.1tTJ'/ 1, }_,,,,i_ 11: l ',)1":dt1 To reire~hcn your mcrnories. and perhap" add :--011wthit1g l<l ehrit_\. I \\Ot1ld like to dt'lirn: and di:-;c11-.,; tt11ll<>r-ho-.t nhti<>'l' ior thl' J>lll'J'"''' ,.f tlii::- p.tjltT. \\ e regard tun1or-l10"t relall 11" I \lr, in tlw older tl'nninohg\-. "~y,;tc1nic cfftct, ni tttm< r,_", a" tho,.t ch:t11ge.- pr()(liict1l in ti,.,u,-.. nt1'1<>te from the ttll1l< r. in \\ hich 110 c\idencc 'i 111''\a,.ta: ic 111alig11ant cell-; i:o found. The~c effect:, ll<a\ he a11atu111ical ,,r L>inclll'111ical in nature. \\'e lnn added llln recl'ntly tlL11 thc1 -.huld he di,01ccd ir0111 the dl'l'Cls of inanitH>!l and :uw111i:,. _\,, i;tir J..:nu'.\'kdgt <>i tumur-hust relations incrc;hc.;, and :001nc understanding io o1ita!llcd oi the mechani:,m of their ]JJ'ud11cti<Jn, \\ e 111ay he'. al >le w talk al'' iut primary and secondary effects. For example, t lie inyo]ut ion oi the thymus gland seems to be sec<Jndary tu an incn;,,cd acti1ity of tlw adrenal (9). Thus adrenal hypcracti,ity \\'ould he cJa,.;l'd a" a ]Jrirnary effect and the thymus i11yolurio11 as 'econdary. Hut it i.; probable that the h_q1crf11nctional adrenal i.;; due to increased pituit;try acti,ity. The adrenal tlien bc1.omes ~c~ondary and the thymus tertiary. It may k that the intrnducti<Jll of the terms primary and sc<:'m1dary 11ould lie useful in organizing the expanding ]Jody ui our knm,:kdge, hut they 11ill he onh relati\e term,,, tu lie di-carded as prugre.;s i,, made. The study of tun1or-ho-;r relations may J,e cJa,,_,ified into thrc< approaches to the problem: (a! the <Je,criptiun oi different t) pe;, of dfrch prudund by the tumr1r, a routine, IJUt nec<::s,,ary catalo.~ue; ( b) atkmph to understand ho\\' the"<:: cfkcb are produced in thl' curnpl.-..:ities of the n1an1rnalian organi~m: and ( c I de1lning the pri1nc cau;,e of the effects. ~ufficiern j, 1101\ kno1\n of (a 1 :,u that 111orc ,.,ork and inforlllatim ;,re Ill'< kd abrJut (Ii 1 and ( c 1, particularly alJout tl1e lattvr. There i.; e1irl<"nce t<> 'upp0rt tlw crmccpt that srm1c material is rekac,('<] into th(' lilo"d "trcm1 fr111 the tll!llor ( l, .21 ), <Jr <m the other hand that sonw co111p<1nent 1wn";1r:' fr1r the normal functi()n 'Ji ti."tH"i i, ah.;tract('(l irom the J;loorl IJy tl1C tlllll'Jr (30J. :\o one has produced a t_q>ical tw11nr lwaring rat li1' the dm>ni1 a<l111mi,,1rat1on (1! a tlllll<Jr e\.tract. .\final \1ord about 'l"'citicit) -;tn)<>!H' 11iv, \1qrk, in 1lw fir-Jr] i' ;,11are that urnw <ii tlw efftch d<''nilwd 1" date an 'J>('l'itic for canc1r: in<l<"l'd if thi' \llT<' "J !lw l1;i,j, i"r a dia~>l"'llt' lt'\l f"r t;rncvr 1u111ld lw <-.1.iliJ1,lHd 1 lt i, pr"lial1l tl:;tt 1lw 111,.ratun <111 d1a~111"'1i, 1<"-.1' i"r c111ccT 11,1, 1i!')t],-d !Jl()rt' to tli(' t11111<>r-lJ<>,t -\l11l1<, 1l1;1n 111 c:111<1r di;1_~11"'h I;-/, _? ~;-