Document N2B7vqJD7j3jrdz7kwMxnGZgb

I'i uc Hexlth M'lM'i.Kvru \n ./" PLAINTIFFS * exhibit Mobil 1 -13 A Quest Into The Environmental Causes Of Cancer Of the Lung T****r? l > DLPARTMKXT I.f HF.ALTH. I-DI L ATION. \nd UKLl-AKE Prune Hf\ltii Sekvicc T T T API 06399 Public Health Monographs edited and issued by Public Health Reports G St.J. PUtfcOTT Ckuf, Dm/MN bf Pmilv Dimta* T*n5 Fcimas Eauor J*vtT V !U*inngr*pb Emi'-''* BOARD OF EDITORS o**o G McCjU'kak. M.D.. 0*pt Hilt C^i***" Lloyd Fiouo. M.D- O1.P.HQf*tr VlRKOM G- MACKtNXtt IF VtcroK H. Haav M.D. Baml C. M*cU**. M.D. M.PH AW IVi Cuy StAo F. Mill**. M D A Quest Into the Environmental Causes Of Cancer of the Lung W. C. Hueper, M.D. Public Health Monograph No. 36 The Author Dr. Hueper it head oj the Environmental Canetr Section of the Saiianal Cancer Institute, Public Health Service, chairman of th, Cancer Prepention Committee oj the International Union Against Cancer, and a past president oj the American Society jor the Study nf Arterioeclerosie. In his SO years oj clinical, research, and teaching experience. Dr. Hveptr has became vxll known, both in Europe and in the United States as an authority on environmental canetr and on arteriosclerosis. He is the author oj more than 200 publications in these and related fields, including the book "Occupational Tumor, and Allied Diseases." published in 191,2. Contents Introduction........................................................... .............................................. General epidemiological considerations.......................................................... Occupational evidence and respiratory carcinogens.. ... Epidemiological data on large industrial groups___ _ . ... Occupational respiratory cancers and carcinogens.. . ... <.-ope of environmental lung cancer hazards......... .. Pattern ami types of respiratory cancer hazards.................. Occupational respirators' cancers............................................ ...... Pliysicochemtral state of atmospheric carcinogens and topograph ical distribution of eanrers in the respiratory tract......................... Specific carcinogens................. ............................ . .. .... Inorganic chemicals . ................................ ... Nickel................. .. Chromium. Arsenic ,. . . . .... ...... .................................... . .. Iron........................................................................................................... Beryllium___ _ . ............................................................................... Orgauic chemicals................. Combustion and distillationproducts of coal.......................... Petroleum, shale oil. andnatural gas................................................ Carbon and silicon polymers.......... .. ... ........................................ Asbestos.................... . ........ ................................... Isopropyl oil . .............................................. ..................... Mustard gas................................. ............................. ............................. Radioactive chemicals .......................................................................... Comments and conclusions.............................................................................. Bibliography....................................... ................. ..................... .................... Pil I I 15 l. IS IS 2t 21 22 23 23 23 2-1 27 29 30 31 31 33 35 35 38 38 39 43 46 API 06401 Introduction ^Hiifitdlly acceptable. any theory f'1 f|)0|opv of lung cancer must reflect a t,4|tnreil and competent analysis of .f,K url, epidemiological. medical, and exih*' evidence concerning the types and prflB"nine11,*l distribution of and contacts ^'hdJ known or suspected exogenous agents **'' tr,, 1 m respiratory carcinogenesis for environmental, occupational, nr medical reasons. It is only through such scrutiny that significant and worthwhile information may be obtained as to the relative role which the various indi vidual respirator?' carcinogens have played and are playing in the production of lung cancer The following facts and observations form an im portant and integral part of surh an assessment. General Epidemiological Considerations 1 n*l. definite, and progressive increase in fluency of lung cancer started in most jjttftrialixfd countries around the turn of the ^uiiy (tables 1-'!>. that is. at a time when ^uriie smoking was still a habit of minor sigAnneal Probst. Berblinger: Grosze. Kthlau: ferhrr: Lirkinti. This nse was first clearly ^gtuzrd by pathologists of Central Europe jjnng the early 1920's through a study of ytropsy data collected during the first two fcsde* of the 20th century and was subse'trntly confirmed and elaborated upon by wsiiusncal investigations from America and farope which mainly used cancer mortality gu fig. 1 Published records indicate that this developmi revealed marked variations in the time i onset of lung cancer, in its relative degree of evenly, and m us progression rate for different sillies and countries. In Germany, for inuurr. an increase in the incidence of lung ncrt was first noted in Saxony and Central (rainy only. .Vs tale ta 1931, Fischer re nted that lung cancer represented U.3 periwof all cancers in Saxony against 6.6 percent * the rest of Germany. In Denmark, accord*fo Clemrnesen, a rise in lung cancer frewy was still doubtful during the first three ***<les of the 20th century and only became definite after 1930. Similar observations as to a late appearance of this increase were made in Italy. There still exist striking differences in the lung cancer mortality rates of different countries and different regions of the same country (fig. 2). In England, for instance, 25 percent of all cancers in males involve the lung; the corresponding figure for N'arwty is less thin 6 percent. Similar discrepancies exist for lung cancer morbidity rates for different metropolitan areas in the United Slates as well as for their relative progression rates (table 4). Another example of the existence of striking regional variations in lung cancer frequency is presented by the remarkable differences in lung cancer mortality rates between urban-industrialixed areas and rural districts. This has been demonstrated for England and Wales and for the United States, where lung cancer death rates were found to be consistently higher in urban areas than in rural areas (tables 5-7, figs. :1 and 4). Such observations have been made in Ohio. .New York, and Connecticut (Mancuso. McFar land, and Porterfield; Levin, Kraus. Goldberg, and Gerbardt) and were reported from England and Wales by Stocks; Kennaway and Kennawav; Fulton: and Philipps. Stocks reported the comparative mortality ratios for males in Health Monograph M. IIU 1 API 06402 Reinhard.. . Fuchs........ Wolf.............. Puller.......... Wolf.............. Perm*.......... Marchess m . Kilcuth.......... Feilcbenleld. Rieebeimann Sehrt............ Marehesani.. Redllch____ Sectaim___ Karrenstein. Kilcuth........ Slaehelio.. Bejich____ Probst___ Seyfahrt... Briese........ Be|ach.___ Bejich........ Mircbeuoi. Hsu............. Berblioger.. Miteroa__ Suebelin... Probst......... Seyfahrt... Assmaoc... Maternal.. Breekeroldt. Riu............. Berblioger.. Probst......... Miteroa__ Kikutb........ Marehesani. Suebelin... Lubarsch.. Setlahn.. . Berblioger.. Materoi... Breckwoldt. Probit......... Suebelin___ Table l. Fmp/ewr nice of lung cnaeen in autopsy material (Probot) Author Period I Number of Total ( Absolute I autopsies 'Carcinomas! No. Lung eaocers Percent of all Percent of all utoptai ' 1859-76 1854-85 1877-84 I 1881-84 ; 1885-84 1885-87 ] 1887-96 . 1888-99 . 1895-1900 . 1895-1901 `1898-1903 1888-1908 1353-1900 1716 1.......... 12,307 4.172 ;................... 9,348 870 7.228 ................... l. 948 5.022 7.790 1.741 3.337 511 711 159 5 ;------------- r atn * ;................... .OK !.................................. a IS. 1.83! .11 3i ..................* 8 i 1.27 .a .14 4 j.................. 10,..-............. * B 22 4.3 . 27 II 11 1.88 1 . . .11 6 !....................... .11 1908-1925 ... 1900-05 1 . 1900-06 ..." 1900-07 | . 1900-11 lQOft-tl 1904-08 ... 1906-10 . 1907-19 1898-1916 ... 1909-13 * 1900-16 ,, 1909-14 .. 1913-14 1913-14 . 1914-18 ` 1913-23 . 1913-23 _ 1914-22 j 1014-22 1 1930-21 j 1 1919-23 2.002 10,272 1 * : 2,739 12.971 6,608 5.801 4. ?JU 4. 816 1 2.347 866 3.448 1.667 6,083 5.518 3,280 4.989 1,809 3.336 _____ 2,429 1.049 j 6.359 3, 697 | 749 496 ' 934 566 715 f 265 . 1.287 692 588 552 363 46 218 389 70 ! 554 580 337 392 94 755 a, 801 287 75 892 502 31 1 32 ! 90 12 20 3 80 i 33 29 6 15 6 I 11 ' 13 5 21 27 10 24 * 146 10 38 456 24 6 26 36 5 6.3 1 1.5 5.1 3 42 .r ,ii 38 : .3? 2. 1 2. 79 i. is 6.88 A 51 . A8 A 95 .11 .9 ti .4 .5 .13 Z7 Z2 Z 08 so .21 .31 .It 3 34 i 11.23 .* J.91 .11 7.14 17 A8 29 .4 .41 S & 12 5. 31 e 3^^ 3 8 M 1 .3 4.9 5. 4 .......... .. 1 & 75 83 * 8.0 Z7 7. 17 . 4.9 , .91 . 5* .4 .9? 1946-49. wit mortality rati Croups of adj occupied dwe London. Ei Binning hat Broome Manchester Liverpool. Leeds. Bra Sheffield, aith NeeceastJe and dvrliingi. -. Aggro***1 of 6 occupied d * Aggregate or 3 occupied d. Aggregate of 40.000 occup Aggregate of 30.000 occup Aggregate of 20.000 occur In Ohio, McFarlane. TabU 2. Fee Author KoS!::::::: gerb*............. Buaehbek___ Purraanns__ Jhmrtns___ Weber mod K bchairer and c p,i*er. Loch r'Wtwl Kaorr ,.r*it Vn< Loch., t-cher;.;;; woeb___ ' From K fblU Beali 2 API 06403 9, with deviations from the average 'tv rate aet at 100, ae follows: of adjacent town* with over 300,000 pied dwellings: 'London. Ext Ham, Vast Ham. Croydon.. Birmingham, Smethwick, Walsall, Waat Bromwich.......... ............................................ Hanehaster. SaUord. Stockport............. .. Liverpool, Bootle. Birkenhead. Wallasey... hoods. Bradford. Halifax.._______________ 154 134 159 152 132 , arilh 124,000 occupied dwaUiu(x______ Haacaitie and Gatesbesd, with 87,000 occupied gj^deeiliafs.......................__ J^Mpegaie of 6 town*, eacb vilb 50.000 to 85,000 X esntpied dwellings-________ ________________ Of 3 towns, eacb with 40,000 to 50,000 if sampled dwellings-______________ ignpu of 12 towns, eacb with 30,000 to 40,1100 occupied dwelling_______ ____________ Igpcgite of 13 towns, eacb with 20,000 to 10.000 occupied dwellings 100 tggrrgur of 29 towns, eacb with less than 30.000 occupied dwelling!................................ 135 II4 113 107 104 89 In Ohio, for the years 1947-51 (Mancuso, UcPadane, and Porterfield), the standardized mortality ratios for lung cancer mortality of selected sites among white males 25-64 years of age in urban and rural counties were: Metropolitan counties (8).................................. 122. 9 Urban counties (71................................................... 81. 8 Rural counties (73)___________________ _____ _ 68.6 The standard mortality ratio is Obaerred deaths Expected deaths ,, ' The type of county is defined, according to degree of urbanization, aa follows: Metropoli tan county--containing cities with 1950 popula tions of 100,000 or more (91 percent urban); urban--containing cities with 1950 populations of 50,000-100,000 (66.2 percent urban); rural-- containing communities with 1950 populations below 50,000 (41.4 percent urban). Curwen, Kennaway, and Kennaway only recently recorded frost evidence supporting earlier observations. The new evidence indi cated the existence of positive correlations between population density in England and Wales and mortality from cancer of the lungs fable t Frequency rales of lung cancers in autoper material of German pathological institutes, 1956-52 Author City Period I Percentage} of lung I eanoen j among all i cancers I Set Male Female Jbcher-Wacclt......... Frankfurt. Bekaimr *nd" 5c"boc" Goettingen. Jena...----- nnii.......... Jwcfabik* ..... ***** od Knolill aeb*^i md Seboe* Berlin.......... Dujseldorf.. Zwickau----- Dresden----Germany... Goettingen. Berlin.......... Zwickau___ Duesaeidorf. Frankfurt.. Jena_______ t*h*r-Wals.... . J"-........................ .................. T3|er and Ein tS:. ..... Hnoli.. Frankfurt.. Duesaeidorf Leipeig. -Bavaria. Duesaeidorf.. Jens........... .. Duesaeidorf.. Frankfurt... Germany___ 1906 1906-12 1910-14 2013-17 1920-33 1924-37 1934-31 1925-33 1927-31 1937-31 1938-31 1931-40 1933 1932-39 1938 1942-45 1945-48 1945-48 1946-47 1946-48 ! 1948 1951 1952 1.6 0.97 6.2 3.61 12 9 19.79 12 0 9.83 15.4 12 0 1128 12 9 12 0 21. 86 12 0 ftft aa ix o 35. S3 32 6 12 94 2 38 21 4 4.8 ; ......................... 234 54 1 From Kablau. **** Health Monograph No. 36. 1*55 API 06404 4 WALE 3 Aj.sa. /Wales ORWAY 4ales DRWAY MALES ? I ; mil** lcmdles *od cancer of the Unas > utsles. *>ut not f females. This relation is i ,tn ipP*reDl wbea comparing relative lung ^acer death r*le* in the United States and gjgjsnd with the relative population density . Jjeae countries. Whereas, in the United ;ties with a population of 45 persons per I ^,,sre mil*. 1 cancer death occurs per [ j^OO inhabitants, in England these figures stand at 753 persons P*t square mil. mil ; cancer death per J.JOO inhabitants. It baa recently been observed that the lung cancer death rate for white males living in the downtown area of Pittsburgh is excessively high--twice the me for males living elsewhere in the city. It is somewhat uncertain whether this observation carries the same implication as the observations made in Ohio and in England and Wales. Such so interpretation is suggested TA* s` Luna Mom rain in owrojMj material af various German iuatltutm of pathology for the period WS-19SS Period i Total caann j i Litof caacen Percent of tan, ea&con smoof all canons Range Average Cjj": 15.131 ua { is}1 * *{ l M2 is ao-7.o ................ Apr-ftdjustcd death rale* far respiratory eaaeer par 100,000 white male* la the United State*, 1950. (Lew) | ...... 1 Oflritr 17 17-20 21-24 25 4 Ovar irland s 1 WALES USA' ALES L AMO :s j_---------------- 146 >950 4Rter of lh U>l hUic Health Mono^oph Mo. BA IMS HIIOS--S3----- 1 S TWf 4. Incidence of mpimon cancer, morftidiiv rate* per 100,000 population for * metropolitan center* by HI. \n~ and 1*41 Morbidity rate* Primary eite and city Male* Females 193* 1947 Pcreeu ioerewe 1937 1947 Percent inrne*e 1937 Total 1947 Percent mere*** Bcoothui and lung: Atlanta.......................... New Orieeru................. Dallas............................ Birmingham................. Denver.......................... San Francisco............... Chicago......................... Pittsburgh........... ...... Detroit........................... Larynx: * Allantt........................ New Orleans................ Dollar............................ Birmingham................. Denver.............. ........... Ian Francisco.............- Chicago...................... Pirnburgh... ............ Detroit..................... * 5. 0 111 19 45 9. 1 15.6 13.3 97 12.6 1.4 11.3 32 1. 4 2.0 4.5 6.7 44 35 13. 4 39. i 39-0 IS. 9 21. 9 34. 3 23. a 36 t 32.0 4.0 14. 9 5. 3 4. 0 4. 1 s. a 7. 0 8. 0 64 168 198 392 320 141 120 132 169 154 186 : 32 66 ms 105 96 4 82 S3 : 1.0 28 .5 2t 4-2 29 4. 3 4.9 23 .3 .4 1.5 0 0 2 *4 .4 4 10 400 4. 2 50 6. 4 1. 180 3.9 86 8. t 93 2 I 108 7.0 63 5.5 12 5.7 148 0.3 1. 0 4 1*3 U .8 .6 .8 .3 150 73 . .... ...... 300 50 too -25 2- 9 8 ft 7.6 20 5 3 1 17 2 3 3 tl 0 ft fi u a 9.6 20 S 18 in fl 7 3 13 6 7 6 in ft 9 2 ft 4.6 7 2.3 2 7 7 2 fi 8 *2. ft 2 4 4- fi 3. 5 3. 7 2. 4 4 4 20 3 4 JOT 174 455 233 1*4 112 105 m 150 1JJ 3t 1 1* < 271 122 . 92 6 83 ' 70 i by the fact that the white male inhabitants also had an abnormally high sloe cancer death rale (Patno). This is in agreement with the general experience demonstrating the dual role played by many occupational carcinogens, such as irsenicals, coal Ur. petroleum derivatives, and radioactive substances in the production of both cutaneous and respiratory cancers. An additional expression of this urban-rural pattern of lung cancer rates is contained in the recent report of Lew, who found that these rates were 30 to 50 percent higher among indus trial policyholders of the Metropolitan Life Insurance Company than among males holding general policies. Lew found, on the other hand, that suck differences did not exist for female holders of the two types of policies. He pointed oul that industrial policyholders represent, for the most part, urban wage earners and their families in the lower-income brackets and include a high proportion of men engaged in manufacturing, mechanical industries, mining, transporution. and personal service. In con trast. the general policyholders are drawn mostly from middle- and higher-income groups engaged in nonhazardous occupations. The apparent causal significance of these epidemiological findings has been demonstrated by several investigators. Appreciable amounts of 3,4-benipyrene have been demonstrated by Waller and Cooper (R. L.) among the air pollut ants of English cities: by Satin and associates in the particulate phase of these atmospheric constituents in Los Angeles, and in the exhaust fumes of gasoline and diesel engines (tables S i and 9). It has been estimated front these figures by Blacklock. Kennawiy. Lewis, and Trqubart that about 16 mg. of 3.4-bettzpyreor t t Table 5. Caneer af tune and larynx. England iJ' Wales 1946-49 (Kennaway and Kenaaway) I Type of community Lues can- Larynx can cer ratio' cer ratio* Melee Fe male* Males Femain . ` * Grenier London............... Counir borough.............. Other urban districts-----Rural district*.----- -------- 100 129 160 233 100 137 156 185 I 100 135 14.* 170 ' Number of peraotu producing 1 death. ICO Si 3 4! 6 Exnnuacalil Cxuct of Cancer af the L* - /torcr n*** i *3 $Uln of the L .-.4, l*1^ tod IW, erui} death rates per r^gsT 3la" IMS ms (odu$tniiid States ___________ 2JS?-.......................................... 8. J 4.5 2-*-"";::::..................... ?. i &<***-i:? gSff:::::::;;:;;;;:;:::;;. ^ fifsn 3. Cancer of the tuttf in males aged 13 veers **d **ff, Co|ltad. I92l40. Reproduced by prrmuMoa of Itw British Empire Cancer Cnpti(n. town 1 0 -uleJ with regional induitrialiiation 1946 1948 E8 7 4 fi. 5 5. 5 7. 3 9. 4 10.0 a 3 3. 7 8. 0 *f ilia* ns< rated **nounti rated br ir potlui. ^sociatai losphcrie e.thiua kblen 8 m thc*r wis, iad nzpvTrne m4 -*> .Agricultural States - 1M6 1948 Sx Vem..................................................................... (dCudiu............................. frith Dakota............................................ Ona---------........................ fcntb Cantina................................ fruhJagtoo...................................... Irauai................................... . 40 ' ,2xx-sSa . . 3X. I1 1 5. 8 1 41 1 3. 4 S. 1 . A9 S. 1 5. 4 XO A0 A1 A4 X7 A3 X9 Tkedmtk ntfi lor the year 1944 were taken from TW Anuncan Cancer Society. Inc.. 1949. Cancer } Hath Rate* (or each state io the Cnfted States by lie. those (or the year 1948 irrre produced by the VauonaJ Office of Vital Statistics. vnv raJi> - ratio1 | (atk i. Luo| cancer mortality nslea. per 1.000 dsilhs bj sex. in Austria, 1954 (HerMcb nod VakoU) Conusumtr I ' Total; Males! k^aitmr^kjftrcat^x^wjfMfrmo^OttnOtmm r n- tt - m > fi Figure 4. Oftwcr* tttd npactod iufemeu dttib* io urban sod rami Ohio, l*47l. (T. F, Mimwo) ...................................... ! 3X 7 i 491 0 12s 52 JSf*1 000 000................i * f 31- L1*" W.OOO-SOOOO.................... 18- 4 ! 3Z 3 ~wader ot Austria..................I IX 3 | 17. J Remainder of Ohio 728 la 017 the : Hank* Moaocmpl. No. , 1955 API 06408 Ttfak I* EiliinAld mmwI 1 of simmUc byiUo- Mifaow an ub|iI of nwlwf exhaust wUb vmcyiac cofinc vmiutiaa spaed* Revolutions per minute Pyrene Com Ban*- : Beni- pound X pynae, Aathaotb ito 300............... 1.000............ 1,300.......... 2.000............ 2.300............ 3.000............ 3.300............ 22i 439 SOT 374 tit 121 48 289 325 286 142 ;' 127 , 23 ' 5 120 1 81 , 33 i 40 ! 25 13 1 10 | 235 i 177 80 73 i 70 ' 85 39 j 153 102 36 27 31 14 13 ' Quantities are exprawed \n *sfa>. at 0 load. miy be inhaled tod retained in the iungs from these sources during t lifetime end that this quantity represents approximately 40,000 times the dose (0.4 microgramsj capable of producing cancer in mice upon subcutaneous introduction. It should be emphasized in this connection that 3.4-benzpyrene is only one of'tbe several car cinogenir chemicals isolated from atmospheric pollutants and that, therefore, the actual total amount of atmospheric carcinogens reaching the lung is considerably higher (Falk and Steiner; Kotin and associates). The benzpy rene content of the air was increased fourfold dunng smog days (Waller). It is difficult, if not impossible, to reconcile the obvious causal significance of this factual evidence with the claim that such regional, and .especially urban-rural, differences in lung cancer frequency are totally accounted for by differesces in the cigarette smoking habit4 of the two population groups or merely reflect local discrepancies in the diagnostic acumen of urban and rural physicians and in the availability of diagnostic medical facilities. Such explanations become eren less tenable in view of the fact that the annual age-adjusted increase in frequency of lung cancer deaths was higher in 1914-30 than in 193)-i4 (table 10). whereas the markedly increased cigarette con sumption during previous years should have boosted the annual progression rate above that seen during the earlier period. It has been suggetted (Liekint: Hammond) that this paradoxi cal behavior of progression rales is attributable to tbe fact that many cigarette smokers did not lire long enough to develop a lung cancer because of their precocious death from coronary sclerosis, which also is assumed to be elicited in , f * r j ( ' ( Table It. Annual ae. adjusted iaetaaae of Ilf fimey of tuBjt caaetr mortality Percent increnec Sex 1914-30> 1831-40' 1933-44' FMeamleas.l.e..!............................... 10. a ao 83 2.5 5- 8 20 * Dorn.. 1 Pottir. Table 9. Estimated amount1 at arenatir hydrocarbon in l-mlnute Minplcs of diced cxbauet with larvin* 1 toad and coftor revolution apoad and with fuel-injection inefficiency (kotin) j Lbe tcc of c Tab l If IV \ Xo Sw. Dc Fra C'ii & Revolu tion? per minute 1.000 1. 200 1, too Load Condition PtTine Com$ ound Bern* prime Beotperylene 0 Compnwatoo release.,........ .... t3;. ....do.................. -. ... . ... ; .... 0 ___ i, ....do-.................... ... ... '5 .... ! . ... *; .. . Q. ___ ___ yh.,1 .... .... 13T 267 538 1.800 2.500 205 257 448 888 1.912 188 177 220 734 822 22 148 22 78 465 42 175 772 124 640 1.320 610 639 876 I. 285 0 9 79 0 *7 40 278 437 I7| 488 432 930 814 1. 706 976 0 80 0 56 78 0 76 1. 372 368 337 982 1.071 346 1.887 044 Anthauthrtne i i 0 43 323 472 459 4.3 24 197 320 044 20 16 69 577 666 i 9 On Lei Ch. bri Ko Mi Jer. Ha 1 Quantities are expnaaed in agm.;min 8 Environmental Camera af Cancer of Ibe Land Pu API 06409 ;n.-0'iniJ for by ^ Hooking babas ,,, or merely reflect piosiic acumen 0f ^ al in tbe availfthilij'1' Siea- f t evrn lee. . i;f i-aies ny i.igarette m*>King. tP*` it*niucal evidence id*0* ^jpiauanon conveniently disposes ^tljoo challenging the validity of the t_% jjjaihulioii of lutit cancer in the .. |1. end Kittled tarrifn countries. Yer Author Mslefemale mio ytocftft*1 uacia----- Omds... (aaluid... 1953 1951 1947 1950 IMS 1951 1941 1951 1949 1941 Dorn............... Moore............ Humphreys... Beeler tl. .. Lmdskof........ Carlisle et at.. K&lpert........... Mcfiumey et *1. O* Keefe.......... F*rbe?o- nd ill 6. 6:1 7:1 11. 5:1 1. 3:1 29:1 14: l 29:1 20:1 115:1 1935 Veelv............ 1953 Steiner............ 1953 Krevtwrg___ 1925 .. .do............... 1947 Henschen........ 1931 Clemmesen... IM5 ., .do___ ..... 1953 ' Denk..."____ 1953 Grosze............ 1850-1899 . .do.............. 1900-1919 __ do... ..... 1920-1929 . ..do........ ....... 1930-1939 __ do................. 1940-1949 ...do................ 1952 Lemolne...... I Mg Gatfnon 1947 Santas. IMS Muon. IMS Fulton. 1:1 1:0. 7 4:1 1:1 2:1 5:4 3:1 15:1 6. 6:1 I 8:1 3-1:1 3. 8:1 1 8:1 8:1 50:1 10:1 7.3:1 Sfrocsn* living in Lot Angeles. cigarette theory and may perhaps momenunlt satisfy the protagonists of thtsiuncepi, although it cannot be taken seriously by anyone who has any competence in the study of arteriosclerosis (Hueper). It is remarkable, moreover, that after a considerable increase in lung cancer frequency in Russia observed during tbe first decades of this century, this development seems to have come to a bait during recent years, according to Anfilogow (cited by Lickint). Considering the recorded strikingly irregular epidemiological behavior of lung cancer in diff erent countries, states, provinces, communities, and population groups, it is obvious that this pattern scarcely corresponds with the patiern presented by the degree and spread of the cigarette smoking habit. If the action of en vironmental carcinogens other than those pos sibly contained in cigarette smoke should mainly account for the remarkable increase in lung cancer frequency and for the causation of u major portion of lung cancers, industrial and industry-related carcinogens would well fit this pattern since the growth of industrial establish ments and tbe use of their products in the economic life of different countries have greatly lacked uniformity in time, type and extent. This concept receives support from a crit ical evaluation of the data on the sex distri bution of lung cancers, the changes in the sex ratio during recent decades, and the probable reasons underlying at least s part of these phe nomena (tables 11 and 12j. Considering the remarkable variations which the male-female ratio of lung cancers has shown at different Table 12. Male-female tea ratio of tuns cancers la Germany, laaa-tftT and 1MO-SO 1886-1927 1940-50 City Auihor , Ratio I City Author R*tio Omdrs. . . .. ft'olf................................. Uw*......... ... Serfarth.......................... Da.... . ... Sehrt............................... , . Brim.............................. fcrius........... . ... Wait]............................... Do........... Da.................... anf............................... Do........... (aria......... .. lamrben____ fca............... laetmrs........ 6 7:1 ' Dresden..................... Lictiot................... 5.3:1 leipsig........................., Knott..................... .... 2.5:1 ........ <JO_______..-..a Merkel........... .... Z9:l Gcrbe..................... ___ 1 7:1 Beilin.......................... Bere...................... 23:1 Potsdam. .................. Ballasan............... .... 1 6:1 Keels.................... Breyer................... .... 5.2:1 Muenebeu............ ...... Aikkn............... .. 4. 7:1 ____ do.................. .. Ksmiseh........... .. .... l. 5: t Fret_____________ 80:1 Jcoo............... .......... Kuntsen................. 1.8:1 Baatburf...-............ Letliua................... .... 11:1 15:1 7:1 19:1 21:1 ? 1 18:1 12:1 the Us* ***> Bmiib Moaosnsh Kb. M. 19S5 9 times, in different localities, ud in different demographic groups, it is most unlikely that such discrepancies and changes are attributable to fluctuations in the intensity of one single (actor, such ss cigarette smoking. Instead, they appear to be due to alterations in the type and extent of the action of a broad spectrum of en vironments! respiratory carcinogens affecting the members of the two sexes to different degrees. The marked and growing predominance of males among lung cancer victims seems to be due largely to the following factors: 1. Males are more extensively employed than females in occupations which produce and use known or suspected atmospheric carcinogens. Also, males work more consistently and over longer periods of their lives in such occupations. 2. Males predominate in outdoor occupa tions. especially in urban areas, where they be come exposed to carcinogenic pollutants in the genera! atmosphere (effluents of domestic and industrial furnaces, exhaust from gasoline and diesel engines, dust from rubber tires and from asphalted and oiled roadsi. . :i. Males more often than females perform heavy physical labor requiring deep and fre quent respiratory movements facilitating the penetration of rarcinogenic air pollutants into the distal portions of the respiratory tract, tberebv inrretsmg the frequency and degree of exposure 5 Males more often than females work through the entire span of their occupational life within urban areas with proved carcino genic atmospheric pollution, while females stay for larger portions of their lives in the cleaner suburban dormitory communities. These considerations provide substantial sup port to the concept that local differences in general and occupational industrial air pollu tants may more plausibly account for an ap preciable portion of the observed differences in ( stuck rates for the two sexes rather than do , local variations in their smoking habits. The doubts as to the unrestricted validity | of the cigarette theory are deepened if critical i evaluation is made of another dubious link in I the chain of claims advanced to bolster this ' concept. It baa been maintained (Graham) . that squamous cell carcinomas of the bronchial mucosa are a specific response to cigarette i smoking since (a) this histological type of bron- chogenie carcinoma was allegedly rare before < 1920; (b) it has increased considerably since that date in relative frequency in comparison to other histological types of carcinoma, es pecially adenocarcinoma; and (c) it is more often found in males than in females. - The facts are as follows: Bronchiogenic ^ squamous cell carcinoma has commonly been found with all known occupational respiratory cancers (uble 13). However, many of these agents have also elicited other types of pul monary carcinomas, such as undifferentiated, round cell carcinomas and adenocarcinomas. Thus, there is no evidence supporting the view that any specific respiratory carrinogen elicits a specific and characteristic type of cancer. A | study of lung cancer records of cases observed figure 5. Ann, f Tahir 13. Hlilolaptal Irpti of occupational rcopiralory cancers. according lo carcinogenic agent Ateat Organ Squamous cell carci noma with or without coruifica I ! Round cell or oat cell carciooma Anaplastic . or polymer- phtt carei- I noma tion ! Adenocsrciooma i V Tar Itmes........................ . ' LUBf................................. Afbestos.............. .................. Radioactive aod dust. Nickel................... ........... tsopropvl oil............ ............. Nana and nasal sinus___ i __ 3 .... 4 ___ 11 H 3 .... 3 ___ q 2 9 3 > 6 4 ... 2* .> 6 \ \ 1*00 M 10 arimomenta! Csum of Cancer of Ihr LnnS Public Health API 06411 before 1920. or even before 1900, readily estab lishes the fact that during those years squamous cell carcinomas of the bronchi were by no means rare occurrences (Wolf, 1895--8 squamous cell Table 14. Coaanmptlon of lobamo la pound* per bead-year. Kn rente nit and United Kingdom. IM6-1950 (Eeeteott) Year Pounds of tobacco per heed-rear iKew United jVilanrt j Kingdom 1000..................................... 1910..................................... 1930..................................... 1930..................................... 1940.................................... 1930..................................... 23 ! 2 69 3.59 . 228 287 : 5.36 1.95 222 299 2 31 297 4.22 carcinomas among IS lung cancers: Probat, 1927--25 percent squamous cell carcinomas ba. tween 1903 and 1918; Watauji, 1903--23 percent squamous cell carcinomas between 1892 and 1899; Adler, 1912--approximately 40 percent squamous cell carcinomas among 181 lung car cinomas collected from the literature with ade quate histological data; Proc. First Nat. Cancer Coot., 1949--44 percent squamous cell caret, L nomas in males; 11 percent in females. ' While adenocarcinomas are more frequent is; females than in males, they also are more fre- . quent in young persons than in old ones (Lind-, skog; Proc, First National Cancer Conf., 1949). * The evidence on hand acarrely supports the l contention that adenocarcinomas arc of endog-. enous causation (Lickint) or that they have an ' etiology differing from that of squamous cell carcinomas (Exeyberg). The male-female sei! Table IS. Aveng* death rere per year par million pmotu (main) from cancer at tfar tuna. 193J-H. New Zealand compared with England and Tale* fEaaleotl) IN Period Country 35-44 45-54 i 1933-36.......................... - New Zealand.......................... .......... 1937-41............................ 1940-41............................ England and Wales........ .............. .......... `3 1 126 87 108 424 A*r 55-44 158 235 802 65-74 204 283 715 75 aed over 1 61 211 441 1943-46............................ 1943-46.................. ......... .......... .......... 1947-51............................ .......... 1947-51. ........................ England and Wale*...................... .......... 46 132 43 166 168 466 635 466 1.072 1.032 287 732 1.014 781 1.662 1.657 121 32? ns 1 i,on 1953-53 ... __ .......... 1952-53............................ England and Wales................... .......... 61 175 305 1.027 1.456 838 2. 171 2.650 1.116 l.SBS I Table 14. Observed and espeeled mortality from cancer of the liu*|t according to place of birth. | Nc Zealand or the Inited Kingdom (Eastcott) .... - - ---------------- --- - ...... .. -.... --t Age at em-y to United Kingdom T: li *> 0 h t t c 8 e V l Place of birth Obaerved Expected deaths i deaths 1' ii Under 30 Observed deaths Expected deaths 30 and over Observed deaths Expected deaths 9 , Xew Zealand.......................... | United Kingdom.................... ; 632 . 369 721- 8 ............................................................................................ . 279.9 201. 229.2 166 139*' Sort: The xlgnlficnnce of the difference between ofaeerved aod expected deaths in the two eoumnes ir p<0.001- v U Fnrirrmmnnlit Cautt of Cancer of the tart API 06413 I T'r'N ' *1. `m "iii rrtu ah`8 ^r. '"Cince, ,j carc|. idles e frequent ,n re more fr<_ 1 on (Lind! Conf., ig49) -upports ^ ire of endog. they here [uamous c|| U*-female lunn. 1932^ tijur''"- in wciecirri ensirvfirrwnui i'*cf>rv lane* " r*. iHjmniidH i. ,-74 75 &nd over 304 3S3 715 635 .033 0t4 657 456 650 SI 2U13l 3saw 735 t.073 1. tio 1. <69 Ucr of birth. lorn id over Expected dtkihs 139. 9 nea is p< 0.001. t of ibc UN jjtio of lung cancer (1:0.7) among Mexican! Bring in Lo Angeles, as well as the ratio of i.S;l for aabestoais cancers (Merewether), do Hi support the view that women have any gonnonaJ protection against the action of enritoomental respiratory carcinogens if identical renditions of exposure prevail. The claim that squamous cell carcinoma of the bronchi is in any specific way related to otarelie smoking thus mar be laid to rest, sure bo special histological type of bronebiopoic carcinoma bears any consistent connection nth any of (he recognized respiratory carrinogens. Finally, it may be mentioned that there doea set exist any parallelism between the annual per capita consumption of tobacco in different nuntries and their respective pulmonary cancer death rates (Herfaich and Neubold; Gilliam} (fig.Si. It has been calculated that the English long cancer rate ia apparently double that of the Coiled States, although the English smoke 3D percent fewer cigarette* per capita than Americans. This interesting and perhaps sig"ificant observation, which fails to support the validity of the cigarette theoty. is disposed of by its proponent* by assuming that exposure to cigarette tar is less sever.- for Americans who do not smoke cigarettes to the very end than for English smokers who, for economic reasons, indulge in this questionable habit. Recent epidemiological studies of EsstcoU in New Zetland provided the most important data on this point. It iraa found that the relatire consumption of tobacco in pounds per head-year for the population of New Zealand and the United Kingdom revealed an inverse relation id their long cancer death rates (tables 14 and 15). Eastcott, moreover, found when comparing the observed number of lung cancer deaths with the expected number fur native New Zealanders of British extraction and for immigrants from the United Kingdom that the immigrant group meets with a much higher incidence of broncho genic cancer than would be expected on the basis of equity, suggesting that the immigrant has an increased susceptibility to lung cancer (table 10). The chances of dying of cancer of the lung are 30 percent higher for all United Kingdom Mb H*hh HUN-49-------1 Ka U, 1955 21 immigrant*. but (or tboM who were 30 years of age or more oo entering New Zeeland, the risk is 75 percent higher, according to Eastcott. Difference* in habits of tobacco smblriog are unlikely to contribute to this picture, in the opinion of Eastcott. Herbich and Keubold pointed out that there did not exist any consistent proportional fre quency between cigarette consumption and lung cancer mortality for Upper Austria and Kaernten, on the one tide, and for Steiermark f and Tyrol, on the other side, although in all l four provinces there prerailed approximately the same per capita consumption of cigarettes. These authors suggested that the high lun| cancer mortality among the people bring in the marginal regions of the northern slope of the i Alps might be related to climatic-atmospheric , Fifurt Rise in annual production or enamunnttnn of earar-nlatad industrial chemicals bclntta IMS and 1*W. recover - UNIT I OTUUMS cost. -rWBUCTKM IN U.S.. mujons or Nrr raw 2 run. Movers-total rnaoucton. thousands or net X Carson Slack -reODUCTNM IN - MUJONS or SOUNDS conditions rinds, wbi sir of Vieo Alpine regie Similsr o prevailing * lung cancel Midlands * ind Neube cancer mor conununitif where the a films from dust and fu the inhabit remote froi rise in lun increase in constructio 0< The com or contribu by epidem eridence ol rates of vs; as well a* specific ant number of well-define> Epidemiol Industrial Epidemilung cancr groups am existence o of persons cancer ofstriking ill list tome o responsible Table If for seven 14 Eariwitl Ciwn nf Cmnw af the Law! NUk Bad IV :,ii na 'Id,. N -l.ho.ieh> ^,,,0114 e-> tie direction of prevailing r , uliitli hnng toe industrially polluted Vienna into the valleys of the northern 1 "Ppfotinn *9 'on of cigaret7> t th* high |7*- ople living ,n t*rn slope of 4tic-atm0sph( ie.1. bei,,n . **7 e regions. yPLlir observations on the influence of the 'eailiofl winds upon the relative frequency of f* cWJcen in different areas of the English Polands trere reported by Stocks. Herbich ^7Veubold. moreover, found that the lung ee'r mortality rates were twice as high in -^unities located along main highways, 7 (he atmosphere waa polluted with exhaust from gasoline and dieael motors and the ^ and fumes of asphalted roads, than among & inhabitants of villages and towns situated ^olt (mm such traffic arteries. In fact, .be ^ lung cancers follows more closely the l*LlSe in consumption of motor fuel and the function of asphalted highways than the consumption of cigarettes hi: n. ' nniiin*:. fig. 7, Hueper i and is similar to tin? increase m production of other cancer-related chemicals. It is apparent from the numerous observa tions and facta of general environmental nature cited (bat there exists an impressive smount of circumstantial evidence of different character and from various sources which stroDgly sug gests tbst several, if not many, environmental factors acting in varying degrees and combina tions causa or contribute to the development of pulmonary cancers and are involved in their recent rise in frequency. Much of the evidence on htnd, particularly the irregular epidemio logical pattern of lung cancer, points to an important role which industry-related factors and the growth of modem industry mar have assumed in these respects. Occupational Evidence and Respiratory Carcinogens H was its* lancer of lb* lee- The concept that environmental factors cause * oootribute to pulmonary cancers is supported ^ epidemiological, medical, and experimental ^jjeoce obtained from analysis of lung cancer out of various occupational population groups M veil is by studies of lung cancers and their strife *nd different causal agents present in a umber of restricted worker groups and in nil-delioed industrial operations. Epidemiological Data on Large Industrial Groups Epidemiological studies on the frequency of tag cancer among members of laige industrial poops and trades have brought to light the eostence of marked variations in the liability W persons engaged in different occupations to near of the lung. Tables 17-10 supply miking fllustrationa of these differences and ta some of the factors which may possibly be "feasible for them. Table 17, winch lists lung cancer death rates ta aareo industrial group* in Ohio, shows a *** Health Monograph No- M. 1954 striking difference between the rates for agri cultural laborers and for employees to the nonferrous metal industry, with rates for trans portation workers occupying a position directly behind the rates for nonferroua metal workers. It seems to be characteristic of inhabitants of agricultural areas to rank first in death rates from cutaneous cancer and last in rates for pulmonary cancer. This is in accordance with the relationship between soJar radiation and Table 17. Uu| raiiew dsalh nla par LOOQ deaths Cram ail eauaaa for 7 Industrial groups la Ohio, S.SM mwlss, 1947 (Manctiao) Industry Death rate MtmfetToiis metal.___ Transportation_______ Rubber and plasties. . Iran and steel..... .......... Minins end quarrying. Agriculture.......... Stone, elaj, glia*......... Total. 3.22 2. 91 134 118 1.53 .82 .68 1.76 IS Fiaurt X. kracitay. T'irnrr .Her: D'fCho Afltj ir-1 Graham: Mrw and nfocillt' lui ktDaaat Bricaaiar.a 'ifiicrhn*. Miller, it i nor? ..-f. D-iO.ir. at': nir? at r 'ira- nnv f.llot. fita'-irar-t ,?nt*nj near of lh* Luna ir-four lune cancer cases were found among 5 000 dock workers at Hull. England, of whom 2.j00 were reposed to grain dust There were to boiier sealers with lung cancer With the urrotion of 1 hoder scaler, none bad any radiological evidence of pneumoconiosia and aoly 5 had a slight degree of pneumoconiosis upon Histological examination No luog can cers were .itiserved among dockers who were ooi rtooeru (o grain dust. it miy be possible urn oo:lrr scalers sustain a carcinogenic txpouir* to rliromate-cooiaming scale, if chromates acre used as anttrtuttng agents, or tbst these workers sustain a pulmonary deposition of non oxide. Whether specific vegetable matter or some carcinogenic contaminant of the gram, web as residues of rbrmical fungicides or other processing ur preserving agents, account for the abnormally high frequency of long cancer among grain dockers is at present a matter for speculation. Mention also may be made of the recent observation of Faulds on the excessive fre quency of pulmonary cencer among English iron ore workers employed m mining activities at two different locations. Necropsies performed on these miners during 1832-53 showed a lung cancer incidence of 9 percent (192 necropsies with 17 lung cancers), while post-mortem ex aminations done on 2,378 males of comparable age who were not employed in these mines revealed that only 44, or 1.85 percent, bad primary lung cancers. It is remarkable that there did not exist any parallelism between the degree of pulmonary fibrosis observed to tbe iron miners and their liability to lung cancer ^aU*c Health Monograph No. 3S, 1955 17 (degree of fibrosis is cancerous lungs, 1 plus; in tuberculous lungs, 2 plus; in fibrolic lungs without cancer and/or tuberculosis, 3 plus). The absence of a positive correlation between pulmonary fibrosis and lung cancer was noted when the evidence on lung cancer among the radioactive ore miners of Joachimsthai and Schneeberg was analysed (Hueper). Although the actual causal factor responsible for the lung cancer among iron ore miners remains to be determined, it may he mentioned that Levin and bis co-workers recently recorded a positive statistical correlation between an occupational exposure to iron oxide and heat and cancer of the lung. - The studies of Breaiow, Bosglin, Rasmussen, and Abrams on 518 histologically proved cases of lung cancer in California suggested the existence of an increased liability to lung cancer for members of the following occupational groups: welders, sheet metal workers, ateamfitten, boilermakers, crane operators, and nonferrous metal smelter workers, that is. individuals who are exposed to metal dusts and fumes; oilers, oil field workers, wipers, and marine engineers, who have contact with oil fumes, mists, and sprays; asbestos workers; construction and maintenance painters, who inhale vapors or various organic solvents, mins, lacquers, plastics, and rubber, as well as finely dispersed inorganic and organic pigments (chromium, nickel, copper and arsenic compounds, carbon black, aniline dyes); and commercial cooks exposed to fumes and mists of overheated vegetable and animal fats and mineral pan greases. A recent study of the causes of death of the members of the International Fhoioengravers i'mon raised the suspicion of an excessive lung cancer liability for members of this occupational group. From ike different lung cancer death rales listed for the various occupational groups, it is obvious that the total number of workers possibly exposed to occupational carcinogens of known or still unknown nature is evidently very large and comprises workers employed in basic and processing industries, construction, trans portation. services, trades, laboratories, and pro fessions (fig. 8). It is, on tbe other hand, equally dear that the quantity and quality of information available on the occupation*! I aspects of lung cancer causation are deplorably defective because of an absence of extensive and prolonged analyses of lung cancer deaths among various industrial groups for specific causal futon. He evidence on hand nevertheless adequate for demonstrating that the wide varia tions in lung cancer frequency apparently existing between different industrial population groups ere attributable to differences in more or lees well-definable occupational exposures ud not to differences in ctgarette smoking habits. Occupational Respiratotj Cancers and Carcinogens Conclusive evidence of the existence of exogenous carcinogens and environmental re spiratory cancer hazards is provided by tbr epidemiological, medical, and experimental data concerning occupational respiratory' cancers. A genera] view of the occupational respiratory cancer panorama, including causal agents, and organs affected is presented in table 19. Scope oj Environmental Lung Cancer Hmarit An indiscriminate acceptance of tbe figure given in table 20 as reflecting tbe actual scope of these identified and recognized respirator)' cancer hazards, however, would be seriously misleading, despite views expressed by several protagonists of the cigarette theory (Ringeru; Wynder and Graham; Levin; ud others). 1 ` Although a definite demonstration of specific , occupational ,,tung cancer hazards has so fat been made for only relatively restricted worker groups, tbe evidence on hud is not only un equivocal but also indicates that other worktf groups exposed to the same causal agents or subjected to identical or similar working condi- J tions are subject to the sime hazards. I" I contrast to the apparently low carcinogen)' potency of the suspected, but unidentified, I agent presumably contained in tobacco smoke, > the occupational respiratory carcinogens I evidently highly potent, as shown by their higb respiratory cancer attack rales (table 21). t Since environmental carcinogens have bees j shown to produce cancers wherever they opei*1* , in adequate intensity ud duration, ud <0* i sidering the fact that muv of tbe occupation*' ^ respiratory car, related general i justly be assure, eent the cause c cfnrers among n lion, especially jupblv industrial Table *> OcTMP* teem Arsenic... . . Asbestos........ Chromates.. Nickel........ Coal tar............. Petroleum oils. Isopropyl oil... . Radioactive chemu Total.... Carcinop Aromatic hydroearl Coal Ur fumes.. Petroleum oils.. Csrbon and ailicon Isopropyl oil... Asbestos___ -MewiAetenip.. .. (.'Iiromates. . Nickel Voicing radUtioo: Radioactive ores is EorlNUwUl Cw of faarae of At tv** ^be Health Me API 06419 fif*wr.v .ari-raoirens occur as industry- "pkfibly it*, general atmospheric pollutants, it may *ir knt) -4i *xnoug -I**,., be assumed that these pollutants repre I trfW. c_a__u_s_e__o_f__a__s__ig__n_i_fi_c_a__n_t__p__o_r_t_io__n^ of lung fic C1aij ^4-rs smong members of the general popula- rthie)j ^ | (Specially those who live and work in "ide industrialized areas. The approximate scope of occupauoaal expoturts to the various respiratory oiauiogcns may be estimated from data supplied bv Bloom field and his co-workers. From a survev of 1.503,304 workers employed in all industries of 10 States, it was found that 7,976 were exposed to fumes sod dusts of chromium compounds and pparentlj. wpuiitiojj us more 0r fa**1 Occupational respiratory uidiufeflj and canmu mgcM during past 75 yean, their causes, sites. usd i ` ' " Hid -habits. Ascot Site of cancer Yeardiscovered Number of recorded cairn United Other States countries Total -wnee 0f leutal re. d by the Qt&l data cancers, spiratory rats, and 9. Hazard^ " figure* iscope of spiratory seriously t several gem; theraj. specific is so far d worker only unt worker gents or g coadirds. In inogenic ratified, smoke, .-ens are uir high ie been roperate od COD- ipational UWOit........ uiesio*..- ...................... Luog............................ ......... ................ ..do...................... ......................... do.................. ................................. do_______ _______ Nates and nasal sinus. jur.................... .................... Luo*............................. rooleum oils.............. ............. . Lung and iarnyx. lurprop.'1 oil....................... Ut&Y.'.... Xaasl sinus. jdiosrtive rhcttucsls.. ..... Luo*-- Nasal sinus. Total. 1930 1934 1932 1932 1936 1936 1946 ' > ; ' 1879 . 1931 ; * l' 32 75 0 0! 0i r: l 4i 8 D. 31 125 i 16 74 65 54 31 53 33 0 0 0 625 0 I. 001 33 96 140 44 51 53 40 t 4 d 625 3 t. 136 Table XI. Respiratorr cancer attack rates, by environmental (smoopM Carcinogen Sites of cancers incidence in population at risk Percent of all cancer deaths Attack rates Rate per 100.000 Morbidity . Mortality .nematic hydrocarbons: Coal tar fumes...................... Lung...................... 500:100.000 Petroleum oils...................... Lung...................... 3.000:100, 000 ' Cuban and silicon polymers: Isopropyl oil........................ {**! *'"*" } 10:100 '. 1m3_4a_.t_5_6_t._5a_)o. r- Asbestos............................ Luog.'.--................................................... -.-------- (13.2-30 percent beatoaia autopsisd . (0.8-3.4 perceat 1 normal)) Detail ; :" . Anuroic............................... .. Lung........................_________________...I-------------- - 145.* males (10-9nor* 1 :! mat) Chromates..........................Lung...........__________ ____ ........................i (42X nor- 146-333 ` mil) ....................................j{ sinuses. HLub|.ss..s........... | i t 574:100.000 .............. ! (20X nor- 1...................................... mal). | faunae redfatioa: j deaths). 4c Laos* PaUie Health Monograph No. 34. 195$ 1* API 06420 3,356. to Fumes end dusts of arienicals. For industrial workers of ftU 48 States, respiratory health hazards existed from the inhalation of dust, fumes, mists, and vapors for 35,000 indi viduals employed in asbestos operations, in 33.000 haring amtact with arsenical*, in 240,000 inhaling various types of metal dust, and in 2.500.000 harm? cutaneous, respiratory, and ingesuve exposures to various combustion and distillation products of coal tar. pitch, creosote oil, soot, and to petroleum fuel oils and lubricat ing oils, greases, and cooling oils, to name a few. The highly defective state of knowledge con cerning theactual number ofoccupational respir atory cancers is. moreover, demonstrated by the fact that information on the existence and cumber of such cancers in specific industrial operations with recognized respiratory cancer hazards is distinctly spotty, not only as to data available from different countries but also concerning those on hand from identical opera tions of the same country. The following ob servations may illustrate this point. The existence of an excessive liability to can cer of tbe lung from en inhalation of coal tar fumes by retort attendants of gas and coke oven plants has been established hr a few re ports from Japan. Canada, and England. Apnrt from these isolated data, no others are available for similar operations from these or any other highly industrialized countries (Ger many. United States. France. Italy. Poland. Russia). Likewise, there is no official record available concerning the occurrence of respir atory cancers among carbon electrode makers and attendants in aluminum manufacturing plants, where workers become exposed to dust and fumes from the pitch and petroleum asphalt in tiie electrodes, and where, according to in formation available from four different countries, ur and asphalt cancers of the skin have been observed as the result of such contacts. It is. moreover, surprising that data on the occurrence of lung cancers among producers and users of arsenical insecticides have been re ported almost exclusively from Europe, al though tbe United States has been for many years the main producer and consumer of these products. Similarly, reports as to iIif existence of respiratory cancer hazards from an occupa tional inhalation of mists and fogs of lubricating and cooling oils have so far totally originated from Europe, despite the fact that American industries offer ample opportunities for identical exposures, that an excessive Lability to lung cancer has been noted for paraffin preisers em ployed in oil refineries, and that the survey of one oil company has shown that there was a marked predominance of operating refinery workers among the lung cancer victims of this particular organization. / Finally, attention may be called to the fact that the entire evidence as to the existence of lung cancer hazards for radioactive-ore minen has come from the observations made in Schneeberg and Joachimsthal. However, mining of uranium ores has been carried on for 10 to 20 years in the Congo, Canada, and the United States and extensive milling operations of tbe African ores have been conducted in Belgium for many years without any official record of similar respiratory complications among tbe workers employed. Additional incompleteness of the existing rec ords on occupational respiratory cancers may be related to the possibility that pulmonary cancers may have their causation from agents entering the body by an extrarespiratory route. While all known respiratory carcinogens are of environmental origin and are inhaled as air pollutants, there exists some suggestive occupa tional. medicinal, and experimental evidence indicating that agents introduced by other routes may be effective in eliciting lung cancers. Several cases of lung cancer are on record which developed after an oral administration of are senicals and which appeared in individuals with arsenical dermatoses and skin cancers fNeubauer). Lung cancers also have been observed in some aniline dye workers suffering front primary occupational bladder cancer (Mdlim } following prolonged cutaneous, digestive, and I respiratory exposure to dusts and vapors of certain carcinogenic aromatic amines. The | possible scientific and practical significance of ^ these findings is suggested by the experimental observation of lung cancers in 10 percent of > rats given the potent carcinogen, 2-acetylaminc | fluDiene by an extrarespiratory mute (Biel* i schowskyj. A cutaneous as well as parenteral | introduction of coal tar and several polycyrlic ^ hydrocarbons as well as of urethane resulted >B SO EaiinniDtiiul Caam of Caaw aT itir la* g precocious a ber of pulmou Pattern and If a map of centration of luiants were p exhibit a son the general i< Dish the over: depth betweei rural districtatmospheric j scribed field irregularly ar shaped *potsuperirapoed It stands to i exposure pan portsnt infiuci acter and inn of various r>carcinogens u oiogicat scau> spread of cai production fo The followi to environmei be distinguish 1. General posurea to c hydrocarbons incomplete cr and industrial exhaust fumeabrasion prod from asphaltarsenical* con of burned coi meial smelte: use of arseni radioactive n front the soil t ing tbe atmt explosions. 2 Special exposure to t PuUic HuUlb Milas--; API 06421 fnr ,h.l,,r TM pr-s5..N `'V ' it-- 5un.,,rri'it lhf>r,. j * '1 -*1"* * C * nmms iS, W "> the r. r `Sls`-nr, ` ",rdrpW" -'SrO "V m'nirKr ",for 10 l0 v ,h" f *4 atIOns of th` '"I frrocj * Among ,h,, '"xisiing r,,, rwr`" mar u Pulmonsrj1 from og^nu r&iory rou,, ifloeens am ol `taJ'-d as occupy. -il Tjdanw hX otbrr <* cancer,. ford which ntioa of arimduaJs n-ith wrprs f\,u. *en observe iffshng from r i.VOiler, mive. and id vapor, ol """PS. Ttlr fmficancr of experimental -* Percent ol etylaminoOute (Bid1 parenteral I polycyclic to-Jr appi aruni-'- iind an miT-u.-ctl numpulmonary tumors in nun-. ogttr11 l,'"` Types nj Respiratory Cancer ` Hazards jf a roP of 'hr distribution and relative '-on* ,ration of the different carcinogenic air pol ' ,n(= "'i-nf prepared for a gtren area, it would &- a fort orf crazy quilt patte__r_n__to ,,wLh.-ic-kh rdt'1 ^oeral atmospheric pollutants would fur* jjU'the overall background color, varying in ^nth between darker urban areas and lighter \pl districts. Other types of carcinogenic ttnospherie pollutants haring a more circum^jbed field of distribution would appear as jpvgularly arranged aod variously sized and j,aped spots and islands of different colors superimposed upon the general background, j, stands to reason that such locally differing fjposure patterns are bound to exert an im portant influence upon the epidemiolopral char ter and incidence rates of pulmonary cancers jl ranoiis regions: each one of the various mrinogens would produce its own epidemi ological scatter pattern showing a diminishing tprrad of cancers from multiple carcinogenic production foci. The following three main types of exposure to environmental atmospheric carcinogens maylie distinguished: 1. General environmental atmospheric ex posures to certain aliphatic and polycyclic hydrocarbons released into the atmosphere as ^complete combustion products of domestic md industrial and ship furls, as pans of the exhaust fumes of gasoline and diesel engines, as ibraston products of rubber tires, and as dust (mm asphalted and oiled roads: exposure to usenicals contained in tbe mineral ash and soot of burned coal and in (he effluents of certain acta! smelters, and related to the large-scale aw of arsenical pesticides: and exposure to tadioacttve materia) either naturally released ham the soil and from bodies of water or pollutiag the atmosphere as tbe result of nuclear explosions. 2. Special and locally restricted atmospheric exposure to carcinogenic pollutants of the air exists in the vicinity of finnierruus nn ial -niclters releasing in their effluents and from their slag heaps fumes and dust containing nickel, arsentrals. chromium compounds, and berylli um. Similar exposure exists in the vicinity of carbon black plants, oil refineries, tar distilleries, gas plants, and similar industrial establish ments producing large amounts of soot or other polycyclic hydrocarbon containing effluents, and in tbe vicinity of rodioartive ore mills and atomic energy plants. The individualized type ol air pollution con nected with the smoking of tobacco, with its suspected carcinogenic hazard to the lung in the special form of cigarette smoking, may be included in this type of exposure to atmospheric carcinogens. 3. During the last 75 years, an increasing number of specific chemical and physical agents have either definitely been recognized or are strongly suspected of being responsible for the appearance of cancers of the nares, paranasal sinuses, larynx, and lung among members of certain occupational groups. These specific occupational exposures are associated with the inhalation of coal tor and pitch fumes and dusts, mists and fogs of petroleum derivatives, soot, vapors of isopropyl oil. that is. the crude liquor from which isopropyl alcohol is distilled: arsenic, nickel, chromium compounds, asbestos, and ionizing radiation. Since the available evidence establishes such carcinogenic connections with only some, but not with all. inhalants, such as silica or coal dust, it is apparent that carci nogenic activities ore not associated with all atmospheric pollutants. Occupational Respiratory Canernt The respiratory cancers of recognized or strongly suspected occupational origin are im portant, not only as industrial disease manifes tations but also as prototypes of etiologically and topographically identical cancers affecting workers in other, similarly hazardous occupa tions as well as of those cancers involving an indefinite portion of the general population sus taining tor environmental reasons contacts with the same industry-related carcinogens. I Physicochemical State of Atmospheric Ojrcinoftehi and Topographical Dittrihution of Cancerf in the Retpriraiory Trad In agreement with observations made as to reasons for the topographical distribution of environmental cancers in other duct systems turogenous and alimentary canal i. respiratory cancers of environmental origin are preferably occupying sites where (o t the flow of the inhaled polluted air is interfered with, that is. in the normal narrow; of the respiratory tract, such as the region of the nasal turbinates and the larynx or its bronchial bifurcations, or (b> where the respiratory tract forms dead end saccula tion; surb as the paranasal sinuses and the peripheral bronchiolar regions of the lung, in which inhaled carcinogenic mailer may accu mulate. condense, and precipitate. The traffic pattern of air pollutant; in thp respiratory tract hu- rorrespond; if the distribution pattern of respiratory rancer- elicited by atmospheric rarrmopeii;. The second principal factor which determines the localization of an environmental canrer within the different sections of the respiratory tract represented by the physicochemical statu- of a particular carcinogen, since this con dition largely influences the site or sites of rhief exposure to-an atmospheric carcinogen Carctnogrnit dusts consisting mainly of coarse pantries are mainly arrested in the Dares, where they cause cancers of the turbinates The nasal cancers obsprred among copper-nickel matte refinery workers inhaling the coarse dust of the roaster; illustrate this interrelation. Tlf excessivt incidence of larynx cancer amons mule spinners inhaling carcinogenic shale oil sprayed from the revolving spindles likewise provides another example of this mech anism because it is likely that the relatively large droplets of this oil are anested in the upper portions of the respiratory tract, making the narrows of the iarynx the part of main exposure Dusts or mists composed of particles having a diameter below 4 microns, on the other band, penetrate into the deeper parts of the respira tory system and therefore are mainly responsible for the cancers of the bronchi. Thp bronrhio- gentc cancers found among chromate manufac turers. asbestos workers, and coke oven and gas retort workers are representative of this type of exposure. Atmospheric pollutants of gaseous and rapor types noi only penetrate into the lungs but also into the nasal sinuses, where (her may be deposited by degradation into solid; (radioactive gases), by decomposition into solids (nickel carbonyl), or by condensation and poly, mentation into liquids or solids (aliphatic epox ides contained in crude iaopropanol liquor*. In assessing the relationship between the physicochemical status of atmospheric raremo- genic pollutants and the localization of cancer- within the various parts of the respiratory tract consideration also must be given to the fart that gaseous and liquid rarrinogens may become ad- I sorbed to the surface of carcinogenically inert solid dust particles and behave under such ton- ' ditions more like solid particles Such com binations. for instance, occur in relation to tht i exposure to radioactive gases adsorbed to rock * dust in uranium mines as well as concerning the inhalation of liquid or solid aliphatic and poly, rydic carcinogenic hydrocarbons adsorbed to the surface of mineral road and industrial dust or of carbon constituting the bulk of soot. The first evidence indicating the existence of causal relations between environmental factors and the development of cancers of the lung was recorded in 1879. when Hirting and Hesse established -the cancerous nature of the lung diseases prevalent among the radioactive-ore miners in Schoeeberg. Saxony. This discovery. _ of historical importance and great present sig nificance. attracted little attention at the time I because radioactivity was still an unknown feet and cancers of the lung were comparatively rare , before the turn of the century and therefore of little medical interest. > It was not until the third and fourth decade; , of this century that additional, well-defined occupational activities and environmental agents were again related to the eausation of * cancer of the lung and other parts of the respint- , toiy tract, that is. the nasal cavity, paranasal sinuses- and iai III!' list of en ,,-ere th<> lung faviurvr; i |9.'i` arsenic workerinrs (19361. tie na;ai sinuses, smelter workii nasal stnusr(|p:tl . the rat and lung ant ilP-JH . and among work' spray- or mt;t- Specific Cart N'ickel.on> tnetai; and p district of Ot alloys (iron, cobalt ; molyi facture o( staforgings, cast; tubing, rods, plating: ratal) pigments in p and so on. Exposure umetallic nirke carbonyl vapo trial workers < lions. While salts not infre' of an appareinhalation of been responsil vote ami of ntonarv manii tion of aiveol exudation ini eosal hptnorrli l the toxic formed from konyl upon tl S3 Environmental Cane of Cancer of the U*l `"Mi* Heehh i API 06423 r-ii.^ muniifa,. own U(l'l g*, I |b ie! larvnx Aiming these atldiiiuns to ii environmental respiratory canrers me lunit ' inert? among chromate manu- of thu iyp. r,f I ^[urers '19-la- of asbesto-i workers ilfkJSi. of mi.- of nspo\)s * 'tLoir workers < I9i0i. and of rolce oven opera- ..-rraip mtn e}lfc ^ ; ipjo the rancers of the nasal cavity, para- i#ey whrre the* :ion into solid* Orion imoo)irt^ -nation and poly, 'aliphatic epo*. mol liquon. p hcuvccn ihf sinuses, and lung among copper-nickel f"ffiepi'ee workers (I932i. the carcinomas of the aasal minuses among luminous-dial painters ig3j'. the canrers of the nasal sinuses, larynx. lung among isopropanol manufacturers .ig-ldi. dn(l cancers of the larynx and lung iniong workers exposed to lubricating oil .p^vs or mists I1936. 19-49). pphcrir rurrtno- at ion. of rancor* ppiraiory lrac( fpccific Carcinogens no the fact that, nay become ad- Inorganic Chtmical* acpnirally inert inder such con~ ';uch com. . relation to tb l?orbed to rock i concerning' ibe >hatic and poly. ns adsorbed to industrial dust ,1k of soot, ibe existence of i ental factors | ,t ibe lung was | ne and Hesse re of the lung radioBeti re-ore This discovery. at present sig* on at the time unknown fact oaratirely rare J therefore of MCKCl Nickel. one of (be most industrially important, mrials and principally mined in the Sudbury district of Ontario. Canada, has many uses: jjoys (iron, copper, chromium, aluminum, lobaiti: molybdenum (employed in the manu facture of stainless steel, heat resisting steels, forgings- casts, wires, sheets, structural shapes, robing, rods. bars, strips, and so om: electro plating: catalysts: ceramic enamels and colors; pigments in paints and inks: storage batteries, tad so on Exposure to nickel fumes and nickel dust of metallic^ nickel and us compounds or to nickel carbonyl vapors is therefore, frequent for indusml workers of many types and in many opera tions flTbtlr skin contact to nickel and nickel nils not infrequently results in the development of an apparently allergic type of dermatitis, inhalation of the volatile nickel carbonyl.has been responsible for an appreciable number of scute and often fatal poisonings. The pul fourth decades t. well-defined environmental e causation of s of the respiravity. paranasal monary manifestations (congestion, desquamauob of alveolar epithelium, fibrinous acellular tradition into alveolar spaces, bronchial mumsal hemorrhages I are apparently attributable to the toxic action of finely dispersed nickel formed from the disintegration of nickel car bonyl upon rile pulmonary structures. Krafft -uggestfil thal ilu-c ri'o' tion.- ar- the r"->ii? .if a nickel allergy having the lung as ns tliu<-k organ. The first report conrerning the occurrence of an excessive number of rancers of the nasal passages (nasal cavity and paranasal sinuses' and of the lungs among workers of the Clydteh plant of the International Nickel Company, located at South Wales. England, was made by GrenM in 1932, although (he first appear ance of these neoplasms among tbe nickel refinery workers was noticed in 1924 (Bsadrrj. Subsequent reports dealing with these cancers were made by Stephens: Amor: Cooper iE. H.i; Carozzi; Bridge: and Merewether. From 1923 to 1948 inclusive, there were reported to the Chief Inspector of Factories a total of 47 cases of cancer of the nose and 82 rases of cancer of the lung from tbe nickel works. By the end of 1948.46 of the workers with nasal cancer anil 72 of those with lung cancer had died. None of tbe patients with nasal cancer and only 2 of the patients with lung cancer had rommcnretl work in the nickel refinery after 1924. when a recon struction of tbe plant bad been carried out The average exposure period for the nasal can cer patients was 23 years (range. 3-26 yearsi. and for the lung cancer patients. 25 years (range, 1-33 years). No cases of cancer of the larynx have occurred, and only 1 cancer of the naso pharynx was observed at CJydaob. The nasal cancers involved the turbinates, nasal septum, aod paranasal sinuses (ethmoidsi. Of these, the majority were of the undifferentiated cell type (6). some showed a squamous cell character (3). while rolumnar cell carcinomas were uncommon (I i Of the lung cancers, of which histological studies were available.in only 4 cases. 3 were of the small cell, pleomorphic type, while 1 was a squamous cell carcinoma. Similar observations were recently recorded from a Norwegian nickel refinery, where 3 cases of lung cancer were seen (Lakeui. In one of these eases a squamous cell rarcinoma was associated with sarcoid lesions. Goldblatt and VTagitaff mentioned that so lar cancers of the respiratory tract have not been noted among the workers employed at the German nickel refinery at Ludwigsbafen, itr of the Lm| hUit Health Monograph No. 36. 1955 a ! Dor has ibere been reported an unusual fre quence of respirator? cancers among tbe work ers of the Sudbury nickel ore mines and smelters in Canada, although several cases of nasal sinus cancers were recently seen in one Canadian nickel plant. Amor pointed out that the majority of indi viduals employed at Clvdacb who developed respiratory cancers were not exposed to the inhalation of nickel carbonyl but to that of nickel matte dust or dust from the nickel matte roaster (Lekeni More recent data communi cated by Morgan confirmed this observation, although exposure to nickel carbonyl vapors bad occurred more frequently among'the af fected workers than was apparent from tbe data previously given by -Amor. The rela tively high incidence of cancer of the nasal cavity indeed suggests that a rather coarse par ticulate dust readily arrested at the region of the turbinates may have been active in the production of cancers at this particular site, while nickel-containing vapors or a very small particulate dust m-*t likely account for the cancers of the lung and nasal sinuses. As to the causative agent, various theories have been advanced. Amor favored tbe con cept that the inhalation from arsenic-containing suifunc acid used in the refining process was the actije carcinogenic agent. It is mast unlikely that this is correct because the nickel refinery workers do not suffer from perforated nasal septa and display no evidence of chronic anenicism such as dermatosis and cutaneous cancers, which almost always have accompanied tbe occurrence of lung cancer among workers exposed to arsenical dusts or fumes (Huepen. Amor stated that the refined nickel-copper ores are free from radioactive matter. The res piratory cancers observed among nickel refinery workers thus are not identical in etiology with those seen in miners employed in the radioactive mines of Schneeherg and Joachimsthal. Workers employed at tbe roasters, in the nickel carbonyl operation, and in other pans of the plant, on the other hand, become exposed to the inhalation of dust, fumes, or vapors con taining nickel. N'ickel is the common denomi nator for all of them. It thus is most probable that tbe respiratory carcinomas observed among nickel refinery workers are reaction products in more or less finely dispersed nickel particles or vapors. There is no evidence available, how. > ever, which indicates that the inhalation of nickel in particulate or vaporized form is ac. companied by pulmonary changes of a pneumo- ' cooiotic nature. , The concept of a nickel etiology of respiratory cancers was tested in animals bv Campbell, who 1 exposed mice to the inbslation of powdered . nickel matte and observed that these animals had a lung tumor incidence significantly higher 1 than that of the tuiexposed control mice. The , recent experiments of Hueper seem to demon strate more conclusively the carcinogenic prop erties of metallic nickel. When pure metallic nickel powder was implanted into tbe femoral and pleural cavities and subcutaneous tissue of 175 rats, cancers developed at the site of injec tion in 50 of them. Whether or not nickel assumes a carcinogenic ' role for cancers of other organs and following exposures by other routes is uncertain. It mar be mentioned, however, that Araki and Mtur demonstrated, by specirograpbir methods, nickel in human and animal cancers of various types and sites. Tbe nickel content ranged from 6.273 mg. per kilogram of fresh tumor tissue to 0J3 mg./kg. ` So assessment of the degree of occupational nickel cancer hazard can be made from tbe data available since tbe number of workers at risk is . unknown. Likewise, no definite opinion can ^ be expressed as to the possible existence and > extent of-respiratory cancrr hazards for persons j having for other reasons contact with dust fumes and vapors containing nirkel or its com- [ pounds. caaoMicst / | Chromium as a metal, alloy, or compound i* used for many purposes in industry. It is for 1 this reason that a large number and variety ! workers have contact with chromium and cbm- mium compoundsand that even restricted group* of the general population may possibly be * come exposed to these agents in the form of dust ` vapor, fumes, mist, liquids, and solids (Bourn* and Rushinj. Workers most likely to be W>* posed to chromium and its compounds arc t acetylene workers, aniline workers, bleacher*- blueprtniei chromate i on makers workers, g ers. pottei battery m ers. ink m ers. pholoi workers, s canizrrs. v welders, u railroad ei stallations An env non with from the rtrial waMrefineric1 catalyst henvironmi follow the agents iti costing o industrial!' a corrosiv and .'or inh developme nasal sept proof of i menting oi lions amoi chromium Factories his report hazards in s well as for it woulis not rec. been dotn relearnt ai This refl appropriai existence individual? 'rial opera lislied data The ob? ^`OnnpciKl **PeciM||y two tyj rhromates u EariroonMmu) Ciam of Gutter of the Lu*f P"tllc Baal API 06425 PartjPi `Jebl* , * 'i form j, T0UPn*C ,of resPir4t0 fi ,anii-v hi^ l mire. Ti. rm > d-n,ofl. mogenie prnfk pU[e mnt,||il> th<> f-nac !,-us *`l<' f inj.v. " -"rinoge*, md folio*,,, rtft'n Iim.r uki and Mlu, ,l,r mvhor|, '*ers of :n ranged fmn, 'imor tissue f occupation*! ' 'm t be dan *s at risk a opinion rss existence ind vis for persons t with dim it*! or us <tim- * compound a try. It is for md variety nf mm and eluo-tricied croup* possibly be e form ofdusi olids i Bourne -;cly to be rJimpounds are ers. blearher*. er of the Irrs i iipnin '`iKrrf..-nromium platers. maiiiifseiuiers. chromite miners, crav- Jn^\ers. dye workers, eiertroplaters. enamel (D v>*\ and pottery frosters. glass rolor- #e**r t0er,- glazers. artificial flower makers, * maker!. linoleum workers, paint raak***^ makers, painters, photographic work- ifi- 'u0|oetiFta,rers- polishers, printers, rubber d*\p steel workers, tannery workers, vula1** ' a-aterproofers of textiles and paper. 0t*"' users of chromate antirust agents in oy. jngines. automobiles, steam beat in- Hdous. and bitumen and oil refinery workers. (ncironmental atmospheric contaminaw chromium compounds may result "D ^ release of chromium-containing induswaste* of chromate plants and of oil . ,,tt using a chromium-containing silica for the catalytic cracking of oils. An * " jjmcnial spread of chromates may also 2j,,w the use of such compounds as antirusting u in automobiles and for anticorrosive (eahag of airplanes. Since many of the ^mindly used chromium compounds exert corrosive action on tissues, skin contact ^d'or inhalation of such agents results in the inlopmeot of chrome ulcers of the skin and gpd septum which in turn provide definite poof 0f *n existing health hazard. Com- on the appearance of such tnanifestaopos smoog workers in new industries using cfeionuiim compounds, the Chief Inspector of factories of England and Wales remarked in k report of 1944 that "the control of old ttisrds in Dew industries is of interest to others * well as to the student of industrial health, lor it would seem that in many cases the hazard not recognized until damage to tissue has km dooe. when old principles have to be niranii and adapted to new uses." This reflective observation seems to be quite appropriate when contemplating the possible nateace of respiratory cancer hazards for diridutls employed in the numerous indus e's! operations for wbicb no pertinent pubUud data of any kind exist at the present time. The observation of apparently occupationTMted cancers of the respiratory organs. `'V'rially the lung, has been limited so far * two types of operations, the production of ^wnates fronr chromite ore and the manu facture "f vrtsin .-iin'mmni piemen i - cm*1 chromate, barium chromate, lead onromute-. In these operations, both water-soluble and insoluble chromium compounds are inhaled by the exposed workers. The chemical nature of the actual carcinogenic agent which is respon sible for the excessive liability of chromate and chromium color workers to cancer of the lung is still controversial. Although all investigators believe that some chromium compound or compounds are causally involved, it has remained uncertain whether the compounds suspected are hexavalent or trivaient, water soluble or insoluble, mono chromates or dichromates. Water soluble chromium compounds (monochromates, di chromates. and zinc chromate) are most often incriminated. Manruso and Hueper recently pointed out that it may be more likely that earrinogenic effects are elicited by chromium compounds which are either not soluble in water or are only slightly so. because such chemicals, when inhaled as dust, would he retained and deposited in the lung and thus exert a prolonged effect upon the pulmonary tissues. Such chromium compounds present in s chromate plant would be represented by chromite ore and its early conversion products preceding the formation of monochromates. These little water-soluble trivaient chromium compounds occur in the material present in mixers and roasters and are contained in the slag which usually is stored for future use in the yard area of the plants. Supporting this concept as to the chemical nature of the carcinogenic chromium compounds is the fact that workers as well as animals ex posed to the inhalation of chromite ore dust have not only a high.chromium content of the lungs but also an excessive blood chromium level (Mancuso and Urone). Recent experi ments on rats which inhaled finely powdered chromite ore dust showed that after 18 months a chromium level of 13.0 and 17.0 gamma, re spectively, in 100 cc. of blood was found in 2 rata studied. This finding, moreover, definitely establishes the fact that a fraction of the chro mium contained in chromite ore is solubilized in the pulmonary tissues and discharged into the blood. N**' Htakli Monofnph No. X6, |95S IS API 06426 Additional support of a causal role of trivalent compounds may be derived from the ob servation that 10 of the 20 chromate workers with lung cancer reported on by Alwens and Jonas in 1038 were not employed within the manufacturing buildings or were repair men or maintenance workera (blacksmith, glazier, driver, welder, or manufacturer of sulfuric and hydrochloric acid, produced in a nearby build ing!. While all of them probably had some exposure io chromates, it is likely that their roman with chromite ore dust or with dust from the slag heaps containing more or less "insoluble" chromium compounds was much mote pronounced (Manruso; 1`rone and Anders: Bourne and Tee: Buckell and Harveyi. As the result of the retention of "insoluble" chromium compounds in the lung tissues, there develops a blackish spotty pigmentation and a spotty fibrous thickening of the peribronchial and interstitial tissue where the chromium dust particles are deposited This pneumonconiotir condition railed chromitosis was described by Andrievskaya and Mislavskaya in chromite ore miners, and by Lukanin; Letterer. Neidhardt. and Kleit and Manruso and Hueper in chro mate manufacturers It was produced experi mentally in rabbits by Lukanin. Letterer re ported a rhronte silicosis in a polisher in an iron foundry olio inhaled silica and rhromtum oxide dust While the attempts of Gross and Koelsrh and of Campbell to produce lung cancer in mice by exposing them to chromate dust were unsuccessful. Srhinz and Vollmann. who im planted powdered chromium metal into the femoral cavity of rahbtts observed after more than : years. 1 animal with cancer of the lung, ami 1 with rant er of the femur. It is definitely surprising [list an excessive liability to lung cancer has been established so far only for chromate workers in Germany (Pfeil; Alwens and Jonas: Teleky: Carozzi: Gross and Koelscb: Alwens. Btuke and JonBs; Lehmann: Martineck: Gross: KoeUrh: Alwens and aaaociates: Goldblatt and Wagstaff' and in the United Slates (Machl; and Gregorius: Gregorius: Baetjer: Hueper: Manruso and Hueper; Impreacia; Division Ttf Occupational Health. U. S. Public Health Serried and in chrome pigment workers in Germany (Baadei Gross and Koelsrh; Letterer. Neidhardt and Kleit). Bidstrup found a single case of lunc cancer upon X-ray examination of the chest or 321 chromate manufacturers employed for more than 10 years in English plants while no date exist on this point in regard to cltnraate-produring or -consuming plant- in otln-i countries, such as Switzerland. Italy, ntnl France. Apart from the excessive frequency of lung cancers among rhromale workers whirh hi cording to American observations, ranges from 13 to 31 times the normal frequency of limp cancers among the general male population. ar> occupational origin of these cancer? is strongly suggested by the shift of the age distribution toward younger age groups This is part nularly striking for the lung cancers present among German chrome piemeni workers, since 50 per cent of the cancers affected individuals before the age of SO years, when lung ranrers of un known etiology are relatively infrequent table oo i The quantitative data on the rhromtum con tent of various organs and blood of persons with chromium lung cancer have been reported by several investigators (Alwens and Jonas: Lct- Tftblr 22. Sac distribution of ease* of chromium eonccrr of the tuna, areordina to tape of *orlrr T* p* of * urker A*e i csr. 21-30 | 31--10 4I-S0 At--00 ttl-70 Tl-fcO Total American chroma ir................................... .......... German chromate...................................... .......... GtrtD&n chrome pigment...*.................. 0 } fc 16 1ft 10 1 5* 3 7 14 12 1 3? 5 3 1 1 ... lerer. Niedlu Hueperu Spi behavior of tl and urine in r the developin' that in chron excretion of rl ment of lung hlood chromi confirmed, th importance in iTfpWlf With the . the nares '* maxillary sinlung was the. observed ant> number of tl 125 cbscs fr> reported as ulcers. Chromium accompany t lung in rhrui farturers L l he pneumom or modifying process or wl of coincident Arsenica Is product of tl zinc, silver, nickel, tin. a in the smelti extensively i tngpast dev vermicides hail, rot poiIv for clearin are applied and are tius Corn, soyheiii ployed as w failure of t bronzing an and cosmeti and its con "Environme for 35.251 26 Efivironomitit Caum* f Gmcer of the Lunf Public Hdlh API 06427 . Viedltartil anil Klett; Mancuso and i esidbliih^il ^ **j,r pannaeet recently noted a peculiar in Genna^ Jj^nor of the chromium content of the blood eky: Csro*^, *2urine in chromate workers before and after ` and Jonil.' development of lung cancer. It was found ch: Aiw*,^ in chromate workers the normal urinary ftptaff) ^ ! 'lotion of chromium ceaaes with the develop- Bd Gregohu,. of lung cancer while simultaneously the dncuw ,nii' fjHd chromium level becomes elevated. If |0ccuptiOn|j \ggrmed, this observation may have distinct rice i and ^ ^portsnee in causal, metabolic, and diagnostic nv (Btadrr. adbardi an^' t0fte'M' . jgjlb ihe exception of 2 cases--1 cancer of of Jun j,r nares (Newman) and t cancer of the the rj,^ (#iJjllary sinus (Goldblatt and Wsgstaff'--the nploi>d [plants "-bile d 0 chro. jjggwas the exclusive site of respiratory cancers ^iwed among chromate workers. The total number of these cancers is at present around 15 n oth^p Italy. and rr of lung which. nr. pcs bom of lung puiation. an > il strangle "atributioo artirularjv lgj esses from all sources. None has been sported ss originating from nasal septum ulcers Chromium pneumoconiosis thus seems to jdompsay the development of cancer of the lung i chromate and chrome pigment manuJsctureis. It is uncertain, however, whether (he pprumonocomotic process plays an essential or modifying role in the specific rancerizatioo process or whether it is merely s phenomenon of coincidental coexistence at among 1 SO perbefore of un- t < table Arsenicals represent a byproduct or waste product of tbe smelting of many ores {copper, one. silver, cobalt, antimony, iron, bismuth, nickel, tin. and lead). .Arsenical) are present Bilim con. 3ns with in the smelter fumes and slag heaps. They are extensively produced and used, especially dur ing past decades, as insecticides, fungicides, and acted by vennicides (sheep and cattle dip, grasshopper Jfonas: Leu twit, rat poison!, ss well as * herbicide, especial ly for clearing railroad nghu-of-wey, Arsenicals wter in applied as sprays to orchards and vineyards sad are dusted from airplanes upon cotton, mm, soybean, and potato fields. They are em ployed as wood preservatives, in the manu Total facture of glass, lead-base alloys, dyestuffs, (mating and paint pigments, and medicinal and cosmetic preparations (Mote). Arsenic ud its compounds constitute, according to "Environment and Health." a health hazard for 35.251 workers employed in American in- dustrtes. Tb ilelinitvlv ts a very conservative estimate ol the number of expoeil workers, considering the long, although incomplete, list of different occupmtions entailing contact with srsenicals given by Chamberlain. The estimate, moreover, does not include the rather consider able number of persons who are exposed to srsenicals for purely environmental reasons by ingesting arsenicals with foodstuffs conurainsted with arsenical insecticide residua, by consuming drinking water polluted with arsen ical! leached into drinking water supplies from mine and smelter dumps, or by inhaling arsen icals released into the air from industrial establishments or by small- or large-scale dust ing operations of arsenical pesticides. From the published evidence, it appears that environmental and nonoccupational contacts with arsenicals have been responsible in recent decades for the majority of cases of chronic arsenicism and cutaneous arsenical cancers iN'eubauer: Hueper: Arguello. Tello. Macola and Manzano: Butzengeiger: Baader; Xieberle; Hofmann; Prell; Holmquist: Montgomery and Wgisman: Cannon: Arhelger and Kremen: Straube; Bohnenkamp; Hatiaer and Simon; Gonnet; and many others). While the causal role which arsenic plays in the production of cancers of the skin on the buis of chronic arsenicism of occupational, medicinal, or environmental origin has long since been firmly established, it is rather recently that exposure to arsenicals has seriously been considered as a principal causal agent of cancers of the mucous membranes, such as those of tbe bronchi, stomach, and bladder. Indeed, today there exists as yet only highly suggestive but not conclusive evidence linking cancer of the lung with an occupational exposure to arsenical dust. However, in' almost all cases of lung cancer for which such claims were made, there existed stigmata of chronic arsenicism in the form of arsenic dermatosis with or without skin cancers. The inhalation of arsencial dust and fumes induces rather frequently the develop ment of perforated nasal septa as well u chronic irritative conditiona of the bronchi, thereby creating a symptomatic cancerigenic pattern similar to that seen in chromate workers. Under such circumstances, the existence of a causal relationship between cancer of the lung >b< Lan# bUt Health Monofrmpb No. H, 1955 3? ) API 06428 and chronic arsenicism appears 10 be a reason able conclusion. Chesi and X-ray examina tions of 40 workers employed in an arsenic smelter revealed a mild degree of pneumoconi osis fSaupe). Although Saupe himself did not. discover any evidence of lung cancer among the workers studied--even though they often were afflicted by hyperkeratoses of the skin and perforated nasal septa--he cited the autopsy observations previously made by Schmorl on 2 arsenic smelter workers who died from cancer of the lung fTelekyi. Frommel briefly mentioned the occurrence of a cancer of the lung in a taxidermist who used an arsenical powder for dusting tbe pelts of animals. Four additional esses of lung cancer in sheep dip workers with arsenic dermatosis noted in one of these were reported by Merewether. while Hopkins and Van Jtuddifard observed in s fanner living near a cotton field sprayed with insecticides, arsenical dermatosis, epitheliomas and cancer of tbe lung. The occurrence of 5 esses of lung cancer Merewether: Hopkins and Van Studdiford' among only 24 individuals suffering from occupational arsenical dermatosis and epitheli omas caused Neubauer to wonder whether this is mere coincidence, because only 2 cases of lung cancer were observed among 143 cases of medicinal arsenic cancers of tbe skin 1Russell and Higher;. or whether under occupational conditions the irritation of the respiratory trart by arsenical dust was responsible for the phenomenon. Henry, commenting on the occurrence of skin cancers among sheep dip workers (1910-231. recorded 2 additional cases of lung cancers among 10 surh workers who bad cutaneous cancers He mentioned, moreover, the pres ence of cancers of the left foot, abdominal wall and lung in a furoiceman in a sodium arsenite factory. Analysing the mortality ex perience of a sheep dip factory, Hill and Fin ing found that ", or 31.8 percent, of tbe 22 cancers causing death among members of this group were located is the respiratory organs, while 3, or 13.6 percent, were situated in the skin There were during the period 1910-43 a total of 73 deaths from all causes among workers in this factory. The proportional excess of cancer deaths was mainly attributable to an excessive frequency of cancers of the lung and akin, which were confined to workers in the chemical processes and were absent among members of tbe general group who would be unlikely to be exposed to any specific hazard. Peny, Bowler. Buckell. Druett, and Schilling concluded from the clinical evidence obtains! that, after many rears of exposure to arsenicah these sheep dip workersmay develops squamour cell carcinoma in the bronchus' The most recent addition to epidemiological investigations on arsenic cancer was made by Snegireff and Lombard in studies of cancer deaths among employees of several metallurgi cal plants of unidentified type. Of the total of 109 deaths from all causes recorded during the last 23 years. 12 were due to cancer of all sites, and of these. 6 were located in the lung! The investigators concluded from this evidence | that "there are indications that biologically tbe human race made the adjustment te arsenic in the environment and that only | rarely, when associated with other contributing I endogenous factors such as systemic disease, j or possibly factors such as radiation, it may be capable of upsetting tbe biological equilib rium"; and further "that the handling of arsenic trioxide in the industry studied does not produce a significant change in the cancer mortality of the plant employees: hence other factors in addition to arsenic must be con sidered significant in the causal relationship to cancer." In view of tbe fart that 50 percent of all cancer deaths among employees of one plant sur veyed were caused by cancer of the lung, the observe lions made in fact strongly suggest * csrrinogenir action of inhaled arsenic trioxide upon the tissues of the lung of the exposed workers. This interpretation of the data of Snegireff and Lombard is supported by the , high incidence of lung cancers among the population of several counties in Montao* where copper smellers and mines were operated for many years, creating an occupational and environmental pollution of the atmosphere and soil with arsenicals. Prolonged inhalation of arsenical dust and fumes appears to produce an increased liabilitv to cancer of the lunf <table 23). ' However, the existence of such connection? i TaMr : County am population Pact Lodge. 1. Silver Ban. 33 Cascade. 41.49* Gallatin, ls.3* ` Personal - The e*tm 10.9 per 100.00 * The av.rl ore and rriea->- slituiid In existed at * histological : arsenicism such evideiu cism among by cancers sinuses, and smokers wit it is most dust, fumes production of these pop The exten types of iror frequent op dust and fu and compou grinders. p> workers. The resul pulmonary respectively pueumwntn and which ible. Tindoes not el marked fib dust also siderosilieos The coes the long ha 38 Emimnnial Cauaea of Cancer of the Lual * Public Heali I API 06429 r Tabic 34. Death* dwr lo caneer of the iunjr anaocv iron or? miam and resident* of MiaaaUi (Brower) H5fr54 Year Number of death. *" Minne sota rest- dpnu St Louisltaaea County miners Minorota resi dent* St. LouiaItasea County minen 1930 .. 1931, ..., !93i. . 1933 . 193-t....... 32* 289 329 367 343 3 11- 0 4 9r 12 11.0 X IX 3 6 n. e 37 6 3a a 90 I 60. 1 60 1 hemaiiii- ntist. Campbell reported an increase in titp number of lung tumors in mice exposed to iron oxide over that of the control series. When the available evidenre is viewed critieallv. it i$ still uneertain whether an exposure to iron dust ronvpys an abnormal liability to lung caneer Although Warren and Drake recently coneluded that the development of primary carcinoma of the liver as a sequela of hemochromatosis apparently depended in part on the intracellular deposition of iron, such considerstions may not necessarily be applicable to pulmonary siderosis and cancer. However. thorough and comprehensive epi demiologies! data on the incidence of lung cancer in workers exposed to iron dust are not available. Hence, a definite conclusion on this problem must be withheld. The availability of conclusive information on this point appears to he urgent, id view of the suggestive evidence recorded hv Faulds and became of the fact that damages have been allowed in the past by rouri action in at least one case of rancer of the lung, in ihe production or aggravation of which the inhalation of steel dust was alleged to have played a significant rale SEaYLLlCM Beryllium is a metal which has found signifi cant industrial use only since about 1920. It was not until about 1940 tbit beryllium and its compounds were extensively employed for numerous purposes and products (berylliumcopper. beryllium-aluminum, and berylliumnickel alloys, glass, phosphors in fluorescent lamps and neon tubes, atomic energy products, ceramics, refractories. X-ray tube windows, vitreous enamel, radio tubes, textile fibers, gas mantles). It is evidently for this reason that untoward effects in persons exposed to the in halation of dusts and fumes of beryllium and its various compounds have been recognized only during the last decade. These manifesta tions were of both acute and chronic nature as far as the respiratory organs'were concerned (acute beryllium pneumonitis, rhronir pneu- moroniotic granulomatous, berylliosis- Some investigator* used the term "sarcoid" in de scribing the histologically peculiar, pulmonary manifestations. It if remarkable moreover. ' that chronic beiylliosis has appeared not only among exposed workers, but also among per sons living in the neighborhood of fluorescent lamp factories and inhaling their beryllium- containing effluents fEisenbud. Berghout and Steadman: Eiaenbud. Wants. Dusian. riicad- man. Harris, and Wolf). Similar observations on occupational beryl liosis were reported from Germany. Italy England, Russia, and Canada. Not mfr-- quently. similar granulomatous lesions have been observed in other parts of the body after 1 the usually traumatic introduction of beryllium ' dust, especially of beryllium phosphors from broken fluorescent tubes. The skin of the fingers and hands was the most frequent j extrapulmonary (oration of these reaction? 1 Beryllium granulomas have also been found in ; the nose and in the anterior ocular structure. | It is noteworthy, that beryllium apparently , oore inhaled is retained over a long period of time in (he human body, since beryllium ha? been detected in the urine up to 10 years after cessation of exposure (Klemperer, Martin, and Van Ripert and has been demonstrated in tin- lungs of rats 1 year after the inhalation of beryllium oxide (Dutra. Largrm, Cholak Hubbard and Roth) as well as in tbeir hone? (Stokinger, Steadman and Root; Barnes - where it may replace calcium. The skeleton retains the bulk of the beryllium in the body (50-80 percent) if the inhaled aerosols arr soluble compounds, sucb as beryllium sulfate and beryllium fluoride; the lungs retain tl>p bulk of beryllium if the compounds are in* soluble, such as beryllium oxide. Experiment? of Aldridge. : shown that certain tissue plasma prot blood. Tlies from hemp p Thp nietab pounds obtai fart that Gat non of osieo intravenously ing powders hum sitieaiquentlr coot and other oxide, bi-ryl. introduced u respiratory t Sissons: Hon; Largent. and period for lit- Comment; osteogenic si of beryllium noted the fa dying with 1able amount following ct years, consi* been exposei pounds of throughout fact that cas been reporieof poorly sol eventuate in sumsbly. tli< would be co rabbits, am over a periowhether per beryllium ar Barnard a coma from possibly be far. only rah upment of administrate direct introd too the femcavity, and 30 Cnviroantenlal Cause* of Cancer of the Laos Public Hsaltf of coal tpitch. tor. soot, creosote oils, anthracene oils, ter oils, sod highly viscous oily tod tern* fractions obtained by the direct hydrogenation at coal employed by the Bergius process). The carcinogenic action of these oombustion and distillation products of cool on man and experi mental animals has been established beyond any doubt. Although the bulk of the casuistic and epidemiological human evidence of occupa tional coal tar and pitch cancers has come from England and Germany, it cannot justly be assumed that American-made coal tars, tar oils, creosote oils and pitches differ fundamentally in their carcinogenic properties from those manufactured abroad. -The exposures sustained by tbe numerous types of American workers in a great variety of occupations and operations do not seem to differ from those found for their European colleagues, nor ore the carcinogenic effects on tbe skin of these workers at variance with European observations. However, in addition to skin contact with these products of processed coal, there exists for some groups of workers a considerable exposure to these agents in the form of dust or fumes (Ur distilleries, ur paint, shingle, roofing paper, paper conduit, and battery case manufacture, gas works, coke oven operations, rood construc tion and repair work, roofing, brickmaking, foundries, furnace attendance, railway engine driving, roundhouse operations, pickling of lumber, chimney sweeping, cork brick manu facture, electrolytic meulproduction, and soon). Since the high boiling fractions of synthetic oils produced by tbe direct hydrogenation of coal through the Bergius process have been shown to be highly carcinogenic to the skin and or subcutaneous tissue of mice and rats, respectively, certain types of workers manu facturing and using sudd products and inhaling fumes or mists of these carcinogenic petroleum and tar oil substitutes may have a special lung cancer hazard. Manufacturing plants using the Bergius process have been operative for some 20 years in Germany and have recently been constructed by several industrial concerns in tbe United States. Not only the environmental, but also to a greater degree, me occupational inhalation of dust, soot, and fumes produced by the incom plete combustion of coil results in the develop ment of a "soot lung," called bitummosis. 32 which is characterized by the deposition of finely dispersed carbon particles contaminated with hydrocarbons normally contained in coal tor in the interstitial lung tissue. Roent genological changes may appear in the lungs after many years of exposure to high concen trations of soot in the air inhaled. While the pulmonary deposition of small to moderate amounts of soot in tbe lungs, such as is com monly found in inhabitants of iadustrialixed regions, does not elicit any appreciable fibrous f proliferations, massive storage of soot particle; | in the lung tissues may finally be associated , with an increase of the interstitial connective tissue and with pseudoglandular formations of j peribronchial alveoli. , Tbe human evidence relating exposure to cool tor and pitch dust and fumes with on increased liability to cancer of the lung is not extensive and is in part controversial. The human evidence relating exposure to coal tar dust and fumes with an increased liability , to canrer of the lung is equivocal. Kennaway and Kennaway stated that, "coal tar in the atmosphere, whether derived from roads, domes tic chimneys, or any other source, does not cause an exceptionally high incidence of canrer I of tbe lung." A similar statement was made by Hugounenq and by Husted and Biilmann ' in regard to tbe liability to cancer of the lung for workers employed in the tar industry and in the construction and maintenance of tarred roads. McLaughlin did not find any lung cancer among 3.OSS foundry workers subjected to clinical and X-ray examinations, although there were 3* deaths from lung cancer among * 64 deaths from all causes.. Menz recently reported that of S3 workers in Swiss gas plants who died during the 1926-46 period. 21. or 22.6 percent, died from cancer of all sites, thereby confirming previous English experience that ( workers in tar and pitch operations have an excessive liability to cancer in general. Iso lated observations of lung canerr in workers exposed to the inhalation of tar fumes were made by Koeloch (blacksmith, tor workeri. Rodenacker (briquette factory worker), and ` Mfillscbitzky (tar worker). In an analysis pf lung cancer deaths among members of different occupational groups for the years 1933-38 Kennaway and Kennaway, on . Environmental Catnea of Cnnetr of the Loaf the other linn, i inn lung; m following orrn pas stokers 2 rrnnr opera toij3fi: printers asphalt workpainters. 120. t and outomohli moreover, n n antone entplnt Additional s viHcd liy the nl generator pas plants ami am Canada uni! E Kownlniia; C'r investigator* ( rnscs of lull.workers win- hot tar fumes , lung rancor ri employed in o; general inrul.i generator gas ' employed. >, occurred in vvr (33 percent apt lung cancers varied from 0 being 16.6 ye: recently made i ers. Of 14 cas workers. 6 wer> cancer of the ethmoid sinuse upper and low- It is likely li rates mar axis Following a vt25 skin canrer' lmd been oltsduring an b-yn of lung cancer, company offirii cancers in litis cases of canrer Front tbe ev the inhalation < of certain open plants, gas plar Public Health M API 06433 ......... P'>-i!inr, * ' onuminh, ntatned in tissue Ro.ri *r in the Iq/ 10 high cone, led. While | U to moderi >ucb as is coJ f iadusrrialijJ irecisble fibro >f soot particl, " be associn u nisi connect)^ r formations ^ ,1it lie i-iiui ,,i Ion 'I * lull an ahnvf-;i\vr:c*' fr-i|Mrn,-v existed for the .......tpnunn# ^:ishoti< workers. 129-. -'>4: gas producers. 202: gasworks operators MS: gasworks superintendents, Tje- primers. 119; chimney sweeps. 119 ' nhnll workers. 164; metal polishers. 174 Winters- 129. tanners. 141: street cleaners. 169 jutomnblie drirers. 149. They recorded. wl>rporer. a ninefold increase of lung cancer ^neitg emplovees of a Canadian gas plant. Additional supporting information was pro.' nded by (be obserrat tons made among Japanese puenitor gas oven workers employed in steel k|*n!s and among gashouse retort workers in panada and England (Kawahau: Kuroda and S' exposure utnes with ^ die lung is nij, rsial. tposure to con eased liabfiit,. I- Keonavar al tar w ihf i roads, domes, irce. does not ence of rancer was made and Biihnana *r of tbe lung industry and ire of tarred id any lung :ers Jubjected ns. although ancer among rnr recently ;se gas plants I. 21. or 22.6 lei. thereby rieoce that a<vabiiia: Cruirkshanfc: Dolli. Tbe Japanese iorrsrigators found, within a 6-year period. 21 rtft$ of lung cancer among generator oven Barkers who were exposed to tbe inhalation of jxu tar fumes when stoking coal. An excessive lung cancer rule was absent among workers fmployed in other parts of the steel mills. Tbe general incidence of lung cancer among the generator gas workers was 5 per 1.000 workers Employed, .'even of these 21 lung cancers occurred in workers aged 40 years or younger 1.13 percent against 15 percent in cryptogenetic jung cancers, tHupperi. Tbe exposure time ttried from 9 years to 23 years, the average being 16.6 years. Similar observations were reeeotlv made among Canadian gashouse work ers. Of 14 cases of cancer among retort house mrkers. 6 were due to rancer of the lung. 1 to cancer of the larynx. and 1 to cancer of the ethmoid sinuses <57 percent were cancers of the upper and lower respiratory tract). It is likely that similar lung cancer incidence rues may exist among American tar workers. Following a visit to a tar distillery where some 36 skin cancers and more than 80 pitch warts ns hare an had been observed among the 300 workers neral. Iso- during an 8-year period, there was found 1 rase tn workers of lung cancer. Subsequent inquiries made by fumes were ar trorfceri. orkcri. and company officials brought the number of lung roncers in this and other tar operations to 6 esses of cancer of the lung. From the evidence available, it appears that atbs among oupa for the nnaway, on the inhalation of tar fumes sustained by workers of certain operations (coke oven, generator gas plants, gas plants, tar distilleries) seem to have an ,,xre-*iiv liahtlitv lo nn> er l" the re-pir-iinrv tract, ft is not unlikely that a more thorough amt competent analysis of the death records of other worker groups, which have so far been found to lark such tendencies, might extend the types and number of tar and pitch workers having an abnormally high respiratory cancer rate. A recent observation of lung cancer in a worker exposed to heated pitch and asphalt points to another source of occupational pulmonary tar rancer of definite practical importance t Pat chi. FCTHOt-ECW. 1IMLC OIL. ISO StTCMlL ati The carcinogenicity of certain high boiling fractions of petroleum and oil shale, as well ns of the combustion products of some of these petroleum derivatives, such as oil shale and natural gas. have definitely been demonstrated not only on experimental animals but also on workers developing cancers of tbe skin after prolonged contact with these agents. Known carcinogenic chemicals, moreover, have been isolated from these petroleum derivatives as well as their combustion products (Berenblum and Schoental: Fischer. Priestley. Ebv, Wattless and Rehner; Falk. Steiner. Goldfein. Breslow and Hykes; Waller; Rehner: Kotin and as sociates.) In addition to skin contact with carcinogenic petroleum derivatives many workers are also exposed for occupational reasons to an inhala tion of oil mist or fumes (workers in paraffin pressing operations, certain groups of oil refinery workers, spinners, metal lathe workers, foundry workers, metallurgical workers, printers, and so on). In spite of this established occupational respiratory exposure to petroleum and shale oils, there are on record only three cases of oil pneumonia among suah workers, although such conditions have rather frequently been obsrrved after repealed medicinal instillations of mineral oil containing nasal drops (oil aspiration pneu monitis or paraffinoma of the lung). In fact, two cases of cancer of the lung apparently developing on the baaia of a medicinal mineral oil pneumonia have been described (Wood; Ssate). The occupational evidence available or pub lished on this aspect of cancer of the lung is rather scanty and in part controversial Kennawav and Kennaway found a relatively high of tbe tiui Nfclic Health Monograph No M, IKS u ratio of laryngeal but not of pulmonary cancer in mulespinnrrs. who inhale a mist of the carcinogenic shale oil lubricating the spindles. Southern noted that tnultspinners occasionally develop multiple primary cancers involving the stomach or the lung in addition to cancers of the skin. Scott, on the other hand, stated that be had not observed a single case of lung cancer among shale oil workers Huguenin. Faucet and Bourdin. who ana lyzed a series of 112 lung cancers for possible etiological factors, found that 18. or 16 percent, were metallurgical workers exposed to the inhalation of nebulized lubricating and cutting oils. 8 were chauffeurs. 5 were mechanics, and I was an engineer. Huguenin and his associ ates concluded that their observations indi cated an excessively high frequency of lung cancer among worker? exposed to vaporized or nebulized lubricating oil. While the study of Gafafer and iitgreaves on cancer morbidity and mortality among the male employees of an oil refining company did not reveal any abnormal liability of tbc members of the occupational group to canrer of ihe lung, this judgment may haw to be revised, at least for certain types of refinery workers according to more recent and scrutinizing observations. Roscb observed three primary cancers (skin, stomach and lung1 in a paraffin worker. Touraine and Bout also attributed the development of pulmonary cancer among certain worker group? to lubri cating oil mists. .Such exposure conditions may account also for the excessivr Jung cancer morialtiy among male metal grinders observed by Turner and Grace There is. moreover some evidence available indicating that tbc inhalation of mists or fogs of certain processed petroleum oil fractions also conveys an increased liability to canrer of the lung During a recent survey on cancer inci dence among employees of a large oil refinery, the surprising observations werr made that there was not only s highly excessive incidence of scrotal cancer among employees of the paraf fin pressing department but that incidence of cancer of the lung was also excessive. Paraffin pressere, who represent about one-tenth of the total employed worker group, furnished 56 percent of the lung cancer observed. Since soot as a waste or commercial product &4 ha? been found to be carcinogenic and to contain known carcinogenic hydrocarbons, a thorough and competent survey of occupational groups particularly exposed to the inhalation of soot (operating railroad personnel; stokers; carbon black manufacturers; rubber, paint, and ink makers; painters; soot burners; printers: diesel engine drivers; carbon electrode manufacturers and users in aluminum plants; smudge pot operators; phonograph record makersi is an urgent necessity. The negative conclusion? ' reached by Ingalls as the result oris survey 0f the carbon black industry are baaed on evident J of dubious merits, because only 79 of the 677 evalusted workers have been employed for 10 | years or more in tbe industry. Since tbc major- , ity of known occupational lung cancer? haw an average latent period of over 10 year?. Ingalls' conclusions arc actually based on 71* living and active workers. It stand? to reason that an analysts of tbe death record? of former carbon black workers may have told a different . story, especially if the diagnoses were based on autopsy findings. .Such investigations would also add to our knowledge a? to the existence, extent, and type of bituminosis which might he expected to exist in workers inhaling finely dispersed soot panicles. ' At the present time, exposure to tsr. pitch, asphalt, heavy fuel oils, lubricating and cutting oils, soot from domestic furnaces, incinerators, industrial power plants, oil refineries, steel plants, metal smelters, carbon black factories, oil dumps and smudge pots, a? writ as exposure to the effluents of diesel and gasoline engines, represents tin- most widespread occupational and environmental contact with carcinogenic material. The specific carcinogrntc agents con tained in these carbonaceous matters are certain specific aromatic hydrocarbons, winch not in frequently are attached to carbon particles giv- k ing rue. when inhaled, to bituminosis or amhra- cosis; or they are constituents of oily matter which, when inhaled and retained in the lungs, cause oil pneumonia or paraffinoma of the lung. Since pure antbrarosis is not causally related to cancer of the lung, the pneumoconioses ac companying respiratory carcinogenesis by aro matic hydrocarbons do not play a primary and eaaential role in this process, although the pneumoconioses may lower the intensity and I ERTironmenkal Cause* of Cancer of ihr Uil 1 prolong the dur carcinogenic rh Since our it been built arou basic carbons r lives, it does it plcre prolcrnr rareinogenir cb prophylactic n praniral ami There is. how. remain? to h.-. are still ratlin maximal anion sure to the rest carbons conui.substance- ni<: t O rb' Rreent stuill dry. Homer. Bose, and IVu a new and in combinations ( through the linkages betwe chemicals and chromosomes, from evidence. genesis by nitn ethyleneinunes view of tbe far by which thespecific action zation. it is asdiaiti? might ntucoprotein? linkage with m by rau*'* miirr action of one meric rnolectth may start a pn followed by a epoxide groups These ronci'l with respiral u reasons. Sinn Druckrey and shown that i various polyi Public Health M API 06435 duces- asbestosis only if ihe inhaled fibers are sufficiently long. In the absence of fibrous structure, the dust is said to be inert (Wyers; Vorwald. Durban, and Pratt). Since the larger fibrils are arrested in the bronchioles (Gardner,, the granulomatous reactions form peribronchiolar fibrous cuffs with giant cells and asbestos bodies. These bare a fibrillar core and an iron staining proteinic or colloidal silicic acid sheath. Whether the iron in the sbealbs originates from the asbestos fibers or is derived from blood or tissue elements is still controversial. These two observations deservp special mention because of the apparent dependence of cancerous changes in the lungs of asbestos workers upon tbe presence of tsbestosis and in vies- of the possibility that tbe proteins of tbe lung tissue may specifically interreact with free groups of the filamentary asbestos molecules fDruckrrv and aaaociatesi. The coexistence of asbestosis with cancer of the lung was first reported by Lynch and Smith in 1935 i'l case. They later recorded 3 addi tional rases ,'Lvnrh and Smith: Lynchi. Simi lar observations harp subsequently been re corded from this country (Stoll. Bass, aod Angrist. 1 case: Holleb and Angrisi. 2 cases: and Homburger, 3 cases): from Canada (Desraeules. Roaseau. Gilroux. and Sirois. 2 cases; Cartier. 4 cases; Rousseau. 1 case); from Eng land (Gloyne. 17 cases: Harrison. 3 cases; Merewether. 31 cases; Cureton, 1 case; Owen. 1 case,, and from Germany (Xordmann. 2 cases; Linzbarh and Wedler. ] case; Homing. 1 case: Welz. 2 cases; BShme. 1 case; Domenici. 2 cases; and Baader. 1 case). Thus, there is at present a iota) of 80 cases o( asbestosis cancer of the lung on record. To this number must perhaps be added Ihe 6 cases of cancer of the lung complicated by asbestosis which Kennawav and Kennawav discovered in an analysis of the death certificates of males registered between 192! and 1936. Eleven additional cases of asbestosis cancer of tbe lung in workers in two English plants were recently reported by Doll, who fell from bis statistical analysis that there exists a definite causa] rela tion between these two conditions (table 25). Mereweiher noted that the mean age of males with asbestosis cancer of tbe lung was 55.2 years (r*Dge 22-72) and that their mean expo- sure time was 20.1 years (range 6-40). while the mean age of female cases was 44.6 years (range 32-71) and their mean exposure time was 7.6 years (range 0.5-48). However, in many cases there elapsed a long exposure-free interval rang ing from several months to 20 yesrs before tbe lung cancer became manifest (Wedler; Wyers-. The age distribution of ssbrstosis cancer of the lung was: Ctmtf tout Alt tuutr 25-54.............................................................. 2 35--4-1........................................................................ 11 45-54.............................................. -....................... IS 55-64........................................................................ 65-75 ........................................................................ 17 5 Tots]............................................................. 51 SiDce lung cancer of unknown etiology orcurs rather frequently before the age of 40 and since 26 percent of tbe asbestosis cancers appeared before tbe age of 44. it seems that there exists s moderate shift toward younger age groups for cancers associated with asbestosis of tbe lung. The exposure lime for asbestosis lung cancer, excluding tbe series of Mereweiher. was: fUil 1 EtfmartUnt (fmrti m\ur%t*t I- 3....................................... ................................... 4 4-10...................................................................... 5 II- 20...................................................................... 21 and over......... .................................................. 4 7 Total............................................................. 21 Tbe exposure time of ibis series covers a wide range (1-23 years), indicating that type and intensity of exposure to asbestos as well as perhaps an individual susceptibility to asbesto sis play an important role in determining the development of this pneumoconiosis and thereby the possibility of a secondary carcinomatous sequela in tbe lung. There were 37 males and la females among the 52 cases tor which information on sex was available. The male:female ratio is thus 2.5:1. which represents a marked shift toward the female side when compared with the usual sex ratio of 5:1 to 10:1 for lung cancers of unknown etiology. Equalization of carcino genic exposure as represented by asbestosis. for tbe two sexes, thus resulted in a trend toward equalization of liability to lung cancer. It is of importance to note that the mean Tcblr 25. Cuuutf Luos cancer '-----Other respiratory ' With mention o! Without menitoNroplajmi. other ' Ali other disease- : All cause-. i locludinp 1 > Including pi * Iccludiof 2 not thoufht to ha< age of 126 not, was only 44.2 ' conclude from these individua tosis before tin develop (Linzh Additional # between asbesv derived Irora tl among 266 cast 1924-46. 31 ca lung (11.65 peror lung cancer years among 6. cent) which cs that asbestosis 14 cases, or 15.2 on which neert the normal ra: ra&trrial was e- Lanza. Vorw: quite skeptical an excessive asbestosis to ) Homburger arChlier investipi cept or ronsii relation as hi (Kennawav: M Hueper; Gross; Linzbacb and I Welz; Doll). The histolog 36 EniiwMUd Cmw of Cucer ( ike Lain* [ Public Health M API 06437 ......... r'n*` ;r*1 cioi** wa* t in mam* r*h. ' r,`*' inet-rval rar.j, v*dff before n* tVriiler: Vy^** **sioi$ canri.,. nj ?`*'*4> r,trn 2 II I; ............ ->t it etiology occur, v of -10 and sine* sneers appeared tat there exists r age groups fnr <>sis of the lung, osis lung ranrpe tlier. was: Cmfbt*#l|( rinm .................... 4 .......... A ................. 4 .............. 21 ics covers a wide : that type and 31os as well aa tilitv to asbesto'letermining the tosis and thereby carcinomatoua females among non on sex was ratio is thus ed shift toward : with the usual ung cancers of ion of carcinov asbestosis. for a (rend toward cancer. that the mean bbt r Ibe Lanf 1 -u--' of Jraib amoac male aabeataa worker* rainpared eiih (be tnurulitv rx pretence ,n' jtl men 2- in Enaland and Wale* (Dali) Caure of death Number of deaths Number observed Expected on England and tt'iits rate* Tret of -jemnranre of ilifferenre hetnepn ob-erverf and expected value of P. lu"f r^mtat<>rv dineaaee < and cardioraaruiar dieeaaets-- <.*!&, mention of asbestwis................................................. it- !* mention of Mbe.it*o................ ........................ '\oasBU, other than lung cancer......................................... ............................................. All causes......................................................................... US -:o. ooougi 14 7. S' } <aooi V )t-l 4 >0 1 39 15. 4 ;U. OOOUU1 --Tjneltidinf 1 ease with pulmonary tuberculosis, t Including pulmonary tuberculoid. i Includinf 2 cases (benign stricture of esophagus and septicaemia) in which asbestosis was present but was ggt thought to hare been a contributory cause of death. ^ of 128 noncotnplicated cases of asbestosis ,"aj only 4-1.2 years (Merewether). One may vorltide from this observation that some of ne individuals apparently died from tsbes^,4 before their lung cancer had a chance to jfrelop (Ltnzbach and IVedler;. .tdilnional support for a causal relation between asbestosis and cancer of the lung is arrived from the fact that Merewether found, among 266 cases of asbestosis observed during 1924-16. -31 cases of coexisting cancer of the lung (11.65 percent), while there were 91 cases of lung cancer with an average age of 59.4 rears among 6.864 cases of silicosis (1.32 permnt1 which came to autopsy. Wedler noted that asbestosis cancer of the lung occurred in 14 rases^or 15.2 percent of 92 cases of asbestosis so which necropsies were performed, whereas the normal rate of lung cancer in autopsy naterial was estimated to be 2-6 percent. Lanza, Vorwald. Warren, and Cartier are all quite skeptical as to the actual existence of an excessive liability of individuals with asbestosis to lung cancer, and Cureton and Homburger are undecided on ibis question. Other investigaLon. however, favor this con cept or consider the existence of a causal relation as highly probable or established (Eennawav; Merewether: Telelcy; Nordmnnn; Hueper: Gross; Lecoeur; Smith; Sails; Wegelin; Linzbach and Wedler; Stoll, Bass, and Angriat; Wei*; Doll). The histological types of lung cancers ob served do not deviate essentially in their relative frequency from those seen in cancers of unknown etiology. There were 22 squamous carcinomas. 7 oat cell carcinomas. 4 anaplastic carcinomas, and 6 adenocarcinomas. In view of the fact that one of the Norwegian cases of nickel cancer of the lung was associated with pulmonary* sarcoidosis, it msv be mentioned that Skavlera and Ritterhoff reported the combination of an asbestosis with a sarcoidosis of the lung which, however, was not compli cated by a carcinoma. Attempts have been made to refute tbe claim of a causal relation between asbestosis and lung cancer by determining the frequency of pulmonary cancer aiming tbe total worker population of the asbestos industry (Cartier: Vorwald). Such a procedure is bound to give misleading results. It is quite immaterial how many workers employed in the industry develop lung cancer, since an undetermined portion of these workers doubtlessly sustains either no exposure or only a low intensity exposure and thus does not develop asbestosis of tbe lung, which is the prerequisite for the subsequent cancerous development. Asbestosis must be considered u the essential stigma of an effective exposure. It is. moreover, necessary to know tbe sex and age distribution of the worker population studied and evaluated as well aa to know the duration of employment and exposure. A marked labor turnover in the industry is not indudve for obtaining reliable information on NU Health Monograph No. 56, 1955 S? the actual number of lung cancers and asbestosis cases which may result from effective exposures. For these reasons, no definite conclusions can be drawn from the observation of Cartier, noting 8 cases of lung cancer among 4.000 workers studied for 10 years, especially as the frequency of ashestosis among effectively exposed workers increases with the duration of exposure fB&hme). Eennaway and Kennaway reported that 8 lung cancers mar be found among 4.000 males of the age range 45-04 years. The evidence on hand, at any rate, has con vinced the West German Government to make asbestosis cancer of the lung a compen sable disease (Tabershaw). The experimental approach to the problem has so far given equivocal results. Vorwald and Karr, using guinea pigs which were exposed to asbestos dust, obtained negative results. Xordmano and Sorge employed mice for this purpose and claimed to have produced bronchiogenic carcinomas with pulmonary fibrosis in two mice This observation needs to be con firmed before it can be accepted. laoeaoru. oil Through the recent discorery of cancers of the paranasal sinuses, larynx, and lung among jsopropano) manufacturers, the occurrence of earbonpolymy cancers has probably been exextended to man. Isopropyl oil--the crude liquid from which isopropyl alcohol is distilled and which is a slightly turbid, viscous liquid, slowly turning, upon standing, into a brownish to Mackisb tarry material--contains polypropy lene compounds as well as propylene ether, whirl may be oxidized into propylene peroxide and propylene epoxide having a tendency to polymerize. Polypropylene, merchandised as Oppono) K. is used commercially as an oil for cable filling. Workers employed in isopropanol manufac ture have been exposed to the inhalation of vapors, mist, and dust of isopropyl oil escaping from leaky pipe connections, defective pumps, and gaskets, or spilled on the floor at the occur rence of breaks in pipelines and during repairs on pipes, pumps, and stills. Weil, Smyth, and Xale reported that, between 1828 and 1850, a total of 7 neoplasms affecting various parts of the respiratory' tract (nasal sinuses. 4: larynx, 3; and lung 1; came to observation among Tl employees, or in S.4 percent of those who worked more than 5 rears in the isopropanol plant. Five additional cases were observed in another isopropyl alcohol plant, making a total of 12 cases, 7 of which involved the nasal cinuses, 4 the larynx, and 1 the lung. It was calculated that the incidence rate-of cancer of the nasal sinuses and larynx for the second group was 134.5 per 100.000, against a normal rale of 6.3, and that the incidence of these can-j cers exceeded the expected incidence 21.3 times, j From the evidence available it is likely that : these cancers as well as those associated with { asbestosis belong to the sew class of "polymer 1 cancers." Mtrataao oas The alleged carcinogenic action of war gas poisoning figured prominently in the specula- , lions as to the cause of the increase in lung cancers observed during the early 19304 (Eikuth: Brockbank; Elotz; Derischanoff, Hunermann; Reiche;. Residuals of warfare gassing were noted by Matt in 10 out of 138 j cases of pulmonary cancer among American I World War I veterans. Four out of 64 cases of lung cancer, recorded by Brockbank. were gassed badly during this war. Macklin noted that war gas poisoning occurred in 5 percent of 164 cases of lung cancer among males, while it was present in only 2 percent of soldiers without this disease. Koelsch con ceded that a few cases of lung cancer exhibited a doubtful etiological relation to war gas injury, which was claimed to have caused also two cancers of the larynx tSpamer: Tillery No distinction was made at that time as to the particular chemical nature of the various gases ( used during World War I. These contentions found little acceptance s< that time. From a carcinogenic viewpoint, special interest has to be attached to the various arsenic-containing gases, especially Lewisite, and to mustard gas (dichlorethrl sulfide;. The arsenical war gases, when inhaled, theoretically may not only cause nonspecific chemical damage to the respiratory tissues but also may produce there a specific delayed carcinogenic reaction. such as that seet with these pasc belong to the gr A possible ct gas upon the h band, may be t radiomimetir efl that demonstra animals exposn mustards of al According to t repts. the caus these cancers ri possibly active i During the I bronchiogenic i. cancer were ni pioyee# of tin Manufact uring Lewisite and Y| workers was 30 old. All three poisoning due (Yamada. Hirothese observatt carcinomatous exposure to mu products deserv While the fui cancers" is a t supported by ai data are aufficie: attention from viewpoint. TL production and natural and ay and cross-linkii rubbers, rosins, brings a consul lation into dire< type. It seemstudy these f coming decades particularly tl system. J?. l*p to some : sure to radioac lively small gt sional workers active ores. in< U Environmental Caotc of Cancer of the UU Public Hntbb M API 06439 ( i..i: .umirijj 7( .r. arinal etcepiionally after skin burns tuesc gases. Cancers of such an origin -f "-h,, j^lpnc <o the group of arsenic cancers. isopmpan^i vc observed Jr) making a total nlvfd the nasal * lung. It v.ai rate of ranrer ,,f for the second leainst a normal nee of these can. ienre 21.3 tunes. >t is likely that associated with lass of "polymer non of tvar gat in the specula. ,/icrease in Jung - early 1920-S Derischanoff; jals of warfare n 10 out of 13% mong American nit of 6-1 cases of rockbank. were '.farkiin noted i in 5 percent among males. - 2 percent of Koeiscb coocancer exhibited i war gas injury, aused also two tv Tilieyi. No time as to the - carious gases [ .. acceptance at i me viewpoint. * J to the carious tally Lewisite. 1 sulfide;. The *d, theoretically hemirfil damage Iso may produce ogeoic reaction. ncer of ihe Long j possible carcinogenic action of mustard ^ upon the bronchial mucosa, on the other jj^Dd. may be related to its cross-linking and ^otnimeiit effect, and may be identical with tli*i demonstrated to exist for experimental $0jiBiJ5 exposed to several sulfur- and nitro- pustards of aliphatic and aromatic nature, ^carding to the mentioned theoretical conrtpi*. >he causative mechanism operative is these cancers resembles in some respects that -^jbly active in polymer cancers. IJuring the last few years, three cases of bronrhiogenic carcinoma and 3 cases of larynx ,.*ni'er were observed among long-term em ployees of the Japanese Army Poison Gas Manufacturing Plant on Okuoo Island, where j^wisne and Yperite were made. One of these corkers was 30 years old and a second. 53 years 4y. All three suffered from chronic war gas poisoning due to contact with mustard gas Viinada. Hirose. and Miyanishit. In view of these observations, the distinct probability of ctrvwomatous effects upon the lung following exposure to mustard gas or chemically related products deserves serious consideration. tThile the fundamental concept of "polymer cancers" is a tentative one and needs to be supported by additional evidence, the available data are sufficiently important to require serious attention from both a scientific and a practical viewpoint. The rapidly expanding industrial production and industrial and general use of natural and synthetic polymerised substances and cross-linking chemicals in plastics, films, rubbers, rosins, adhesives, textiles, and so on, brings a considerable part of the working populauou idto direct contact with chemicals of this type. It seems to be advisable, therefore, to study these population groups during the coming decades for the occurrence of concern, particularly those affecting the respiratory intern. Radioactive Oumiealt Up to some 10 yean ago, occupational expo sure to radioactive agents was limited to rela tively small groups of industrial and profes sional workers (miners and refiners of radio sINesnUviec Hoereaslt;h inMdounsotgrriaapl haNndo. mMe,d1ic9aSl5 consumer* of radioactive suiirtatitc---j;tr ttiar.i!,- ni.ir.'jfacturcrs. luminous dial point its. rs>ii tube makers, physicists and their assistants, radiolo gists and their assistants). Sure me advent of successful atomic fission and the ready produc tion of synthetic radioactive subsianre*. the number and variety of individuals who have occupational contact with radioactive matter hare rapidly and greatly increased (uranium and thorium ore miners, smelter and refinery workers, atomic energy plant employees, mili tary personnel, and agricultural, biological, medical, chemical, meiallurgic. oil. pharma ceutical, and other industrial research workers employing radioactive isotopes, as well as operators handling directly or indirectly ma terials or technical devices giving off ionizing radiation, such as radioactive static eliminators (Silson; Berman and Ernest; Bryan and Silver man), sewage disposal workers, paper and textile manufacturers, and so on. It is an established fact thst cancers of the skin, connective tissue, and bone and blood forming organs have resulted from exressice exposures to radioactive substances affecting the organism or parts of it by various routes. There exists a great deal of highly suggestive, if not conclusive, epidemiological and experi mental evidence relating an occupational in halation of radioactive dust and gases to the development of pulmonary cancers. Although excessive medicinal and occupational exposure to ionizing radiation (radium, X-radiation) alone may produce in man and experimental animals a fibrosis of the lungs (Ealbfieisch: Doenecke: Belt; Bergmann and Graham: Engelstad: Warren and Gates; Leach. Farrow, Foote and Wawro; McIntosh; Warren and Spencer; Widmann; Bauer; Bauer and Schraer; TfingeS'and Ealbfieisch; Freid and Goldberg), occupational exposure to radioactive dust and gases has often been complicated by simul taneous inhalation of dust containing various metals (chromium, nickel, iron, arsenic, cobalt) as well as silica. Pulmonary cancers observed among radioactive-ore miners, therefore, have been complicated in an appreciable number of eases by silicosis of a minor to moderate degree. It is for these reasons that the radioactive genesis of the cancers of the lung noted among these miners as well as among uranium and API 06440 radium refinery workers has been doubted by Mini' mvesttgaiors. who frit that one of the various nonradioart ive metals or the silicosis represented the main causal or an important contributory agent fSchinz: Lorenz: Schmorl: Rostoski and Saupe i or that the available evi dence did not provide absolute proof of a radio active genesis (Larassagnc. Several investi gators fell that the lung cancers among the radioactive-ore miners in Schneeberg and Jo achimsthai acre principally attributable to a hereditary predisposition Treated by inbreeding of the mining population (Marklin and Marklin: Lorenz: Vesui-. _ The "mala metallnrum" causing death at an early age of the miners in the ore motmtoins of Saxonv teas first described hv Agrirola during the early part of the I61I1 century and was sub sequently mentioned by other investigators CHenckel: Ncheffler: Thiele . However, it was not until 1679 that its malignant neoplastic character was corrertlv recognized (Harluig Dd Hesse This judgment n. subsequently confirmed by Cohnheim: Aurke: Arnstein: Uhlig: Risel: Schmorl: Beyrouther; Rostoski. Saupe and Schmorl: 1-ange: Neitzel: D&hnert: Baader: Telekv: Hueck: Rostoski. .Saupe. and Schmorl: Tbielr: Weber: Koelsch: Linde- mann: Doubror: Brandt: Brezina. Although the miners of the uranium orp mines in Jo- acbimsthal (Czechoslovakia! also were suffering from a fatal lung disease similar to that observed among the cobalt ore miners in schneeberg. Saxony, it was not until 1926 that the cancerous nature of the pulmonary disease among these miners was recognized fLovrv), Additional confirming evidence was provided later by Beutel and Waldrirh: Ziel: sikl: Saupe; Peller: Firrhnn and >ikl: Baader; Bebounek and Fort: and Telekv. Evidence supporting a radioactive origin of the lung earners among these two groups of miners was provided by the observation of lung cancers among employees of radium refineries and radium laboratories. L6wv reported the occurrence of two such cases among the workers employed in the laboratories of the Joachimsthai mines, where the ores are refined and the puri fied material is tested. One of the rases had chronic radiodermatitis. leukemia, and lung cancer. A similar observation was recorded by Telekv and bv Xeitzel in a Gemitm technician I of a radium laboratory. The cancerous lung 1 was found to be radioactive. Four cases of lung I cancer have recently been observpd. according j to Baader. among the workers employed in the I radium ore processing plant in Belgium, where the occurrence of such complications was pre viously said to he absent (Maisin. cit ing Delaei . Perhaps the development of a bilateral alveolar carcinoma of the lung in a woman 16 years aftei the intravenous injection of 75 cc. 0/ Thorotrusi may also supply suggestive evidence that lung j cancers may originate from radioactive motprtul | used medicinally, when such materials become arrested in the lung. I Mention may also be made in this r-onnrrtion ; of a report of Martland relating the occurrence of cancer in tbe ethmoid cells in a luminous dial painter, and of two additional rases re- ; ported by Auh. Evans.' Hempelmann. and Martland Dial painters not onlv ingested radioactive materia! which became deposited > in tbe bones and produced osteogenic sarcomas, but they also inhaled ibis matter wbirh. thus, may have produced the carcinoma of the paranasal sinus. . The four cases of cancer of the lung recently * reported in an industrial population at in ' atomic pile site, however, are definitely not causally related to any specific radioactive ex posures sustained by the workers concerned. In these cases exposure and latent period were insufficiently long to cause lung canrer (Love:. On the other hand, the argument that thesr workers were, in part, not directly concerned , with radioactive material carries little weight. Doubtlessly, they bad at times environ mental contact with such a materia) when the meieorologic conditions were unfavorable for the ready dispersal of radioactive wastes at ibis particular operation. < In favor of an occupational and radioactive origin of the lung cancers among the Schneeberg and Joachimsthai miners is. moreover, tbe fact that the excessive liability to pulmonary neo plasia is limited to the workers employed under ground and is absent among the workers employed aboveground, and among the popula tion at large of Schneeberg and Joachimsthai. including the employees of the cobalt pigment plant usmgthe Schneeberg ores(Bauer; Schmorl). excessive lung not beer, found at' Johann Georgcu* have a low rode more, no valid es of arsenic-, ehrew containing ores at s rate even rem among the two m The attack rat M lineeberg null' 1 worn fU' of rite Joachim SI 1 range from 4f' " incidence rate nu recent statcniciii during the perio-. of lung cancer said,1 disease? an :tJ.i miners entj'l" critic the fact 1 period of lung 1 range* from to I* sullied that the?1 in a miner popul -tnti members wo U*2ii and 1930. . at M-lmeeberg is war- ior the maji ally to be as short Seiiraub. and K The total nunt died from cancer 1939. according < approximately 4* acltirrsthal miner has reached 22. number of these at a relatively n- data given in ttr the definite shift Measurements Schneeberg and oust rated that, h have mi excess'1' passing many tin t-Joachunsthal 3 Bchounvk and I Lorenser: Lam h was suggests of pneumatic di 46 Eaeinmmalal Carna of Canter of tfar Lnnf Public Health M01 API 06441 greater significance in ibis connection are the findings of Lisco and Finkel, who found meta plastic aDd neoplastic proliferations of the bronchial epithelium in rats inhaling an aerosol of radioactive cerium. Similar results were obtained with plutonium brought into the lungs of rats. Since uranium ore miners inhale not only radon and radium dun but also uranium, which mar be retained in the lungs, Hueper, Zuefle, Link, and Johnson injected metallic uranium powder dispersed to lanolin into the pleural and femoral cavities of rats and obtained sarcomas at the sites of injection in 13. or 24 percent, of the 54 rats surviving the minima! latent period of 6 months. Evidence thus produced shows that focal accumulations of uranium, which is an alpha-radiation emitter, may exert a cancerigenic action upon the surrounding tissues, but it does not discriminate beta-pen the influence of metai toxicity per ae and radioactivity in the genesis of these lesions. From a critical evaluation of the epidemio logical clinical, and experimental evidence available, it appears that a prolonged inhalation of radioactive gases and'or dust may elicit pulmonary* cancers in man (Martiand; Evans). In commenting on the production of lung cancer by atmospberic carcinogens, an editorial lLancti. 19521 remarked, "radioactivity of Joacbtntsthal mines is stated to be 30 Umes the tolerance dose. It is scarcely surprising, there fore. that in the past more than half tbe miners died of lung cancer." It stands to reason that this effect on the lungs of workers will prevail wherever similar conditions of exposure to radioactive gases and dust exist. The excessive suicide rate observed in the past among the miners in Joacbimstha) (Siklt aptly reflects the human nuserv produced if such hazardous working conditions are permitted to persist. While there thus can belittle, if any, doubt of the principal role of ionizing radiation in tbe production of lung cancers among radioactive ore miners and similarly exposed occupational groups, some comments on the possible signi ficance of pneumoconiosis in eliciting or modi fying this effect may be indicated. Reports on the occurrence of pneumoconiosis among the miners in Schneeberg and Joschims- thal are contradictory. While Scbmorl as well as Rostoski. Saupe. and Scbmorl in tbeir early reports (1926. 1925) noted that .Sclmeelieig miners suffer from more or less intense anlbracosilicosis and that this condition was causing or fivoring tbe development of the bronchial cancers. Rostoski and Saupe staled in 1930 that pneumoconiosis was usually not very extensivr in cancerous lungs. Because of the relatively alow course of tbe pulmonary tumors. Rostoski and Saupe felt that pneumoconiosis may slow the intrapulmonary growth of tbe tumors. Hueck, on the other hand, remarked that silicosis does not represent a precancerou? con dition for the Schneeberg lung cancers. -Some of the miners had silicosis but not lung cancer, while others bad lung cancer but not silicosis. Similar discrepancies seem to prevail con cerning tbe Joacbimstha] miners. Ziel in 1935 reported that marked silicosis among these miners is quite frequent and that asbed lungs I contain large amounts of silicon oxide. Pircban ' and Sikl. on the other hand, maintained that no l pneumoconiosis could be found, in spite of an , abundance of pneumatic drilling, and that pneumoconiosis has no role in the production of tbe lung cancers. This opinion was shared by Lowr. Sikl. in his most recent communication j on the subject, stated that some degree of j fibrosis suggestive of silicotic origin could, of i course, be seen in the cancerous lungs, and there were single cases of marked silicosis combined with cancer. On tbe whole, however, silicosis was not a prominent feature in rases of cancer: on the other hand, the lungs most heavily affected with silicofibrosis were generally free from malignant growth. Bebounek and Fort noied that' pneumoconiosis was recorded as tbe cause of death in only E.2 percent of 63 miners who came to autopsy between 1929 and 1935. This statement contrasts strikingly with the observations made by Saupe during a chest X-ray study of 39E Joarhimstbal miners a conducted in 1939. He found that 43.4 percent of these miners presenled roentgenological evidence of pulmonary silicosis. However, silicosis was of minor degree among the V miners who were suspected of having pul monary neoplasma. Although the data are in part contradictory, it seems that silicosis does not play any sig nificant role as a direct or contributory cause of rancer of the lung among the radioactive- ore miner:- ui Whether it tm* canrerizatmn | the establish.-. Finally, it m cancers vary a iurr. Many < others, round while a fp* . The radioacti' this respect t other orcupnti- The rapidly radioactive m tinned, ntorke limited work. population to . radioactive nr represents a )> of serious prop cancer from su lo past expen ores. Theref. the degree c>f active conton neighborhood and operation supervision rc> active effluent men is, are urj the health of t Tin- i-omps analysis of th and cxperinietuous refpirn1 leave no dnut occupational general pnpuh contact? villi For most o sive proof of by epidemiolt data. One 43 Environmental Causes of Cutter of the LhB| FnUie feftlth !TI<xllUirt inn r*WSmi{ the hni-hilt 10 'lu>*'**b*,rtr and Ji'iichimsihuJ. . ijj,r it ha? an antagonistic effect upon tbe **^rull,ln process or modifies the course of 1 pstablisbed cancer rrmama problematical, oil in 1910 iKi, ^finally- it niay be mentioned that these lung very exiensiv, vary a great deal in histological struc- ,f the relative^ ``y Many were squamous retl carcinomas; Table 26. Latent periuri* of environmental re-piratore rancera, in muatba iHtieper) Cancer of -- Agent Lung Narer and naaal muse* irnors. Rostoslij ilosis may stii% ,{ the tutnooir* remarked lhat cancerous cancers. Jintnt iot lung cancet< t not silicosis. precai) con. - Ziei in 1935 *7^ round cell or anaplastic carcinomas; *Tjjf a few were of adenocarcinomatoua type, f^diosctive lung cancers, thus, follow in respect the genera] pattern set by all ?er occupational cancers. jjk rapidly growing production and use of ijosrtive material and the thereby eondi- ' markedly increased exposure of some jjpjttd worker groups as wrell as the general population to gases, dusts, and mists containing Atrnge Range Aveng* Rante latent ot latent latent oflatrr period period penod periov Asbestos............ ....... 18 Chromates.________ 15 Nickel--.................. Tar fumes.............. 22 16 Isopropyl oil................. looming radiation... 25-35 15--18 --......... .......... 5-47 .......................... 6-30 11 3-26 9-23 ........................... 10 .6-16 7-50 25 19-32 among these Jsdicaccive matter of long half-life doubtlessly Intensive studies also are needed for deter .at ashed lungs "presents a potential respiratory cancer hazard mining whether, through radioactive fallouts, side. Pircbtn 11tamed that q0 in spite of an 0I Krious proportions. The attack rate of lung osBcrr from such sources is very high, according B past experience with miners of radioactive the inhalation of highly radioactive dust par ticles diffusely settling in tbe bronchial mucosa and producing there minute foci of high inten mg. and that gps. Therefore, a competent assessment of sity radiation may elicit delayed cancerous e production of vras shared by .omniunicittots nine degree of rigin could, of ungs. and thert oosis combined wever. silicosis sses of cancer: degree of exposure to atmospheric r&diopctive contaminants for worker groups and Mtgbborhood populations of radioactive plants pid operations, and the continuous and strict aipernsion concerning the amounts of radio active effluents emitted from such establish ments, are urgently necessary for safeguarding the health of these individuals. reactions. Since radiation cancers, like other occupational cancers, have a long latent or induction period (table 26), it is essential that all possible precautions be taken against en vironmental contamination with radioactive matter to prevent a possibly permanent con tamination of the human environment with dangerous amounts of radioactive matter. ost heacilr dneraUy free .nek and Fon ;S recorded as percent of 63 Comments and Conclusions ween 1929 and strikingly with tpe during a mstbal miners 1 43 .4 percent Tbe comprehensive panoramic view and ualysis of the total epidemiological, medical, tad experimental evidence available on exog- chemicals has been isolated from several agents representing variable chemical mixtures tsoot. coal tar and pitch, petroleum oils, gasoline and ,-nigenological However, .imong the 7 toous respiratory carcinomas and carcinogens leave no doubt of the fact that not only large occupations! population groups but also tbe diesel engine exhaust). Wherever a definite identification of a specific causal agent, such as isopropyl oil, asbestos, and chromates, has having pul- patera] population have definite and prolonged not yet been attained, the epidemiological evi contradictory, play any siglUtory cause of e radioactive- contacts with one or several of these agents. For most of these agents, adequate conelu- sre proof of their carcinogenicity is provided by epidemiological, medical, and experimental fata. One of several specific carcinogenic dence based on an evaluation of cancer inci dence of relatively small, occupationally cir cumscribed total populations at risk is suffi ciently reliable to prove the presence of an occupational respiratory cancer hazard causally r of the Lattf HkUc Hodtfc Meoecnph N*. S* 1*55 45 r-;jr. -i <i a .panne industrial operation. Epi<i-nui>ioL'i<'al medical. and experimental data . on' ernme these respiratory carrinogens attest ihnir high rarcuioeenic potency under occupa tional conditions, particularly when acting on humans. It is therefore reasonable to assume that inhalation of the same agents, in a miti gated form as air pollutants, by the general population is responsible for a considerable portion of the lung cancers attributable to such contacts. If this coherent and logical picture presented by the evidence supporting the various occupa tional respiratory cancers and. especially, the coal tar fume cancer of the lung, is compared with that available for the cigarette smoke lung cancer, even upon superficial examination, several additional serious defects and inconsis tencies not previously pointed out become apparent. It is surprising to note the absence of positive statistical associations between lung cancer and cigarette cough, although this latter symptom is clinically characteristic of chronic chain smokers. Despite the fact that the lips and oral mucosa are constantly bathed in the tarry liquor oozing from the tip of the cigarettes and despite the contact of these parts with the smoke coming from the cigarettes, there is no consistent statistical association with cancer of these parts. The assertion that no tarry material exudes from the cigarette tip is belied by the evident fact that chronic cigarette smokers are observed to have brown-stained fingers. There is. on the other hand, not a single record available of cancer, of the fingen attributable to cigarette tar. Such cancers of the fingers would be equivalent to the numerous coses of coal tar cancers of the bands for which records are available. In an attempt to provide as explanation for this discrepancy in the carcinogenic behavior between coal tar and cigarette tar, Lickint resorted to the speculative assumption that cigarette tax possesses a special tissue specificitv so that the skin of the first three fingen. although impregnated with cigarette tar, is immune" to its carcinogenic action. It also would be medically unsound to con clude upon a sort of racially conditioned tissue umnuniiv for explaining the observation of Lipsehitz. who reported in f'iwt 'If iv-ip*, records of a large Jewish hospital in tVansw ft* Poland, showed a lung fancer frequent-v of | pr percent of all cancers for Jews against a fee. 1 c*vl quenev of 13.3 percent for non-lews, espenallv o! in view of the fact that Eastern Jews are par. ticularly prone to develop thromboangiitis obliterans, which has the best established causal relations to tobacco smoking. The claimed absence of a positive associi tton poi Ur ol th* between lung cancer and the habit of minding ; cigarette smoke also is inconsistent with the I rule that the incidence rate of occupational * cancers increases with the intensity of exposure ' to a carcinogen. The medical consideration* on cigarette smoke cancer of the lung thus ^ reveal a number of serious and fundamental ( defects and contradictions. The best that can be said about the ex}wn- | mental evidence on hand regarding carcinogenic .* properties of tobacco tar is that it indinnes the i carcinogenic agents in some cigarette tars ` through the use of hyperreactive animals | There is no evidence that these observations of | the skin of a strain of selectively inbred mice have any equivalent in man. Thus the prac tical importance of these observations as to cancer of the human lung is at present uncer tain. especially since Passev. io recent experi ments on mice painted for 16 months with tobacco tar, was unable to elicit a single cancer of the skin. From these considerations, it is apparent that any final decision concerning the relative role of cigarette smoking in the causation of cancer of tbe human lung should be kept in abeyance until a great deal of additional and more valid, and especially medically conclusive, evidence becomes available. The data on hand make it unlikely that cigarette smoking repre sents a major factor in tbe production of lung cancer and in its recent phenomenal rise in frequency. For these reasons, it would be most injudicious mainly to base tbe future preventive control of lung cancer hazards on a theory of such doubtful scientific merits and to concen trate the immediate epidemiological and experi mental efforts on this apparently overprop agandized concept. Tbe apparent wisdom of such an attitude is readily apparent from the fact that not only a great deal of the circua- Eaytme--nl Csam ml fnnt rf tba Leaf API 06445 I Bibliography Adler. I.-. Primary malignant growth* ol the lungs and bronchi. Longmans, Green A Co.. 1913, p. SB. London AtartdtfTTr. Barnes. J., and Deni. F. A.: Experimental beryllium poisoning. Brit. J. Exper. Path]. 30; 875 368 (1H9Ahrens. W.; Her Cfaromatiungenktebs. Proe.. 3th Internal Kodkt. I. Vnfallmed. u. Berufskrankh.. Budapest. 1938 Leipiig, Georg Thieme, 1939, p. 973-982. Alwens. 77., Baulee. E. E.. and Jonas, W.: Audalleade Hiofuoa eon Bronehialkrebs be! Arbeltern der ebemiscben Industrie. Arrh.f. Geirerbcpath. 7; 68 84 (1936 . 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B.: - iriih cicarette 1953). ' mniihi. M An mm found in m mi tnumimrd mm* i. " -= bei den BersJinik 31: 1535 I 'eon* maligner lurch Drurkreis ` ! Path u Current Title* Public Health Monographs No. 19. Medic*! service are** tad diatuces traveled for physician care in western Penoaylvania. Antonio Cioccu mod laidore Altman, i Public Health Service Publication .Vo. 248) 1954. 32 pages. Illustrated. 25 cents. (Published concurrently with Public Health Report] 69: (3): are page* 321-322 for summary article.} No. 20. Gamma globulin in the prophylaxis of poliomyelitis. Report of the National Committee for the Evaluation of Gamma Globulin in the Prophylaxis of Poliomyelitis. (Public Health Service Publi- - cation .Vo. 358) 1954. 178 page*. Illustrated. 41215. (Published concurrently with Public Htabb Repatu 69: (5): tee pages 519-520 summary.] No. 21. Why some sanitary engineers leave the field- Irwin M. Rosenstock and Arthur P. Miller. (Publie Health Service Publication No. 359) 1954. 16 pages. lUusiraled. 20 cents. (Published concur* rentlr with Publie Health Reports 69: (9); see pages 865-866 for summary article.) No. 22. The BetbesdaiBallerup group of paracolon bacilli. Mary G. West and Philip R. Edwards. (Public Health Service Publication No. 362) 1954. 35 pagea. 30 cent*. [Published concurrently with Public Health Reports 69: (10); see pages 1012-1013 for summary.) No. 23. Biological factors in the tranamiaaioo of American arthropod-home virus cncephahtides. Frederick F. Ferguson. (Public Health Service Publication No. 372) 1954. 37 pages. 30 cents. (Pub lished concurrently with Public Health Repans 69: (11); sec page* `1095-1096 for summary.] No. 24. Appraising the clinical resources in small hospitals. Faye G. Abdellab and Eugene Levine. (Public Health Service Publication No. 389) 1954. 39 pages. 30 cents. [Published concurrently with Public Health Repons 69 (12); see pagea 1215-1216 far summary.] No. 23. Sickness experience in (elected areas of the United State*. Selwyn D. Collin*. Katharine S. Tranlbom, and Josephine L. Lehmann. (Public Health Service Publication No. 390) 1955. % page*. Illustrated. 50 cent*. [Publiabed concurrently with Public Health Report* 70: (1); eee pagea Bl-82 for summary.] No. 26. A history of plague in the United States. Vernon B. Link. (Public Health Service Publication No. 392) 1955. 120 pagea. Illustrated. 60 cent*. (Publiabed concurrently with Public Health Reports 70: (3); see pages 335-336 for summary article.] No. 28. Tularemia in abeep and in sheep industry workers. Tilliim L. Jelliaao and Glen M. Kohl*. (Public Health Service Publication No. 421) 1955. IT pages. Illustrated. 20 cents. [Published concurrently with Puttie Health Rtpotu 70: (7); see pages 720-721 for summary.) No. 29. Mortality from cancer in the United States. Harold F. Dora and Sidney J. Cutler. (Public Health Service Publication No. 418) 1955. 121 pages- Uluttrated. 65 cents. (Published concur. ready with Public Health Reportt 70: (7); tee pages 721-722 for summary.] No. 30. Major causes of illness and of death in six age period*. Selwyn D. Collins. Josephine L. Lehmann, and Katharine S. Trantham. (Public Health Service Publication No. 440} 1955. 22 pages. Illustrated. 25 cents. [Published concurrently with Public Hmlth Report! 70: (9); see page 857 for summary.] No. 31. Illness and mortality among infants in tbe first year of life. Selwyn D. Collins. Katharine 5. Trantham. mud Josephine L. Lehmann. (Public Health Service Publication No. 449) 1955. 20 pages. Illustrated, 13 cents. [Published concurrently with Public Health Reports 70: (10); see page 1028 lor summary.] No. 32. Disposition of first sdmitsiouf to s State mental hospital. Morton Kramer. Hvman Goldstein. Robert H. Israel, and Nelson A. John son. (Public Health Service Publication No. 445) 1955. 25 pages. Illustrated. 25 cents. [Published concurrently with Public Health Report! 70: (11); tee pages 1135-1136 for summary.} No. 33. Survey and appraisal methods for community fly control program!. H. F. Schoof. (Public Health Service Publication No. *43) 1955. 18 pages. Illustrated. 20 cents. [Published concurrently with Public Health Repent 70: (11); tee pages 1137-1138 for summary.) No. 34. Housing rehabilitation and enforcement of housing laws. Ralph ]. Johnson and Roy O. McCaldin. (Public Health Service Publication No. 451) 1935. 34 pages. Illustrated. 30 cents. (Published concurrently with Public Health Report! 70: (121: set pages 1247 1248 for aununary.J No. 35. A study of selected borne care programs. Alice M. TTaterhouse. Eleanor C. Bailey. Jeanne T. Palmer, and Mary C. Gillis. (Public Health Service Publication No. 447) 1955. 128 pages. 65 cents. [Published concurrently with Public Health Reports 70: (12is see pages 1249-1250 lor summary.] No. 36. A quest into tbe environmental causes of cancer of tbe lung. V. C. Hueper. (Public Health Service Publication No. 452) 1955. 54 pages. Illustrated. 45 cents. [Published concurrently with Public Health Report! 71: (1); see interpretive article. i * j ! * I API 06457 ll.lv d. I L. itlOD hed -T21 and 418) irur. for i D. lam. iges. -^1* wyn jan. izes. cillh non ihnget. tilth JO. *ith ,ry.j h J. 1IQQ bed *e, lie Us. C. ith 1 l 1 t * Public Health Monographs arc -dilrd and t-sued by Public Health Report! under the grnrrat directum ..I the Board of Editors. The monographs present ronlributiims In L1nn.le.l2e in thr fields of public health, particularly material that is cvtrn*ive. detailed, or specialised. All manuscripts considered for publication as monographs receive thr same trchnical and scientific review as paper* submitted to Public Hmlth Rep.>ru. Thr opinions represser! are those of thr authors and do not necessarily reflect the views of Public Health Report! or thr Public Health Servirr. Trade names are used Tor identification only and do not represent an endorsement by the Public Health Service. luthort will facilitate review if they submit three copies of their manu script*. double spared, with each page beginning with a new paragraph. Public Health Monographs are listed in the table of contents of the issue of Public Health Report! with which they are concurrently published. They are alao listed in its annual index, in the Quarterly Ctmularite Index Medicus American Medical Association), and in the Current Liu o] \ledical Literature Armed Force* Mediral Library), Single copies of most Public Health Monographs ate available upon rc< quest to the Public Inquiries Branch. I'. 5. Public Health Service. W ashington 25. D. C. Orders for quantities should be sent to the Superintendent of Documents. I'. S. Government Printing Ollire. Washington 25. D. C.. wherr they arr available at the prices shown, with a 23-percent reduction on orders for 100 or more. In ordering, give title, monograph number, and Public Health Service publication number and enclose rash, rhecL. nr money order. Stamps are not acceptable. 1 fcPl 06458