Document RJwLMDVxpJ6DEopvBJjR7EKpa

FILE NAME: New York State & NY Times (NY) DATE: 1952 DOC#: NY011 DOCUMENT DESCRIPTION: Journal Article - Survey of Some Current British and European Studies of Occupational Tumor Problems [Author - Dr. Smith of NY] i j\ hi -t " T4r ^" ?' - *' l ;,F si U-Jit - I*. > U- Tfy nDi-wM: f-h. Vf r UUeW<./.i SURVEY OF SOME CURRENT BRITISH AND EUROPEAN STUDIES OF OCCUPATIONAL TUMOR PROBLEMS W ILLIAM E. SMITH, M.D. NEW YORK p j x JU N E 28, 1950, I sailed from Xew York with the object of visiting indi^ viduals engaged in the study of occupational tumor problems abroad. Experi ence gained from these visits provides the material of this report and will be presented under the following headings: I. Shale Oil II. Petroleum III. Asbestos I \ . Dyestuffs \ . Sources ui Statistical Data on Occupational Factors in Cancer. I. SIIALE OIL Skin cancer.- m parafhn workers in the Scottish shale-oil industry were noted as long ago as 187(>. In 1923, a detailed study ot this problem with a report of 65 cases was prepared by Dr. Alexander Scott ' at the request of the Scottish shale-oil industry. Dr. Scott has continued since that time to serve as medical consultant for the industry and as works physician. 1 had the privilege of visiting him at the Pumpherston Works in Mid-Calder, Scotland, where 1 also had the pleasure of meeting Air. Alan Anderson, the works manager. Dr. E. Smith, the chief chemist, and Air. Crombie. works chemist. Mr. C'rombie gave me a tour of the plant. He stated that oil shale, the material taken out ot the earth., is retorted at lGO'd to 1900 F. at four plants in Scotland to yield naphtha, ammonia, and crude oil. The products are then sent to the Pumpherston Works, where thev are processed to yield gasoline, industrial naphthas, paraffin, diesel oil, coke, .and acid sludge.- The paraffin is obtained by a pressing operation, to be commented on in more detail later. Presented at a meeting of tile Cancer Prevention Committee in Xew York. Oct. 18. 1950. Dr. Smith is Assistant Professor, Department of Industrial Medicine. Pust-t iraduate Medical School. Xew 3 ork University. i Travel expenses involved in the preparation of this survey were met by grants from the Anna Fuller Fund and from Xew York University. 1. Scott. A.: On the Occupation Cancer of the Paraffin and Oil Workers .if tile Scottish Shale Oil Industry. British M. J. 2:1108-1109 t Dec. lU 1922: The Occupation Dermatoses of the Paraltm Workers of the Scottish Shale Oil Industry, with a Description of the System Adopted and the Results Obtained at the Periodic Examinations of T h e s e Workmen. Eighth Scientific Report. Imperial Cancer Research, Fund. London. 1923, pp. 1 94: Shale Oil Industry in Occupation and Health. Report Xo. 242, International Labour Office, (leneva. PUS 2. A Brief Description of the Operations of the Scottish Shale Oil Industry, Scottish Oils, Ltd,, Glasgow, 1948. (32 pp.) 242 YU During tL work has reu he made I n s . dermatitis. A' which 1 saw : been exposed Case 1 ( ID varying size ami The erythema h C ase 2 (Dei in (d is c 1. T h e scars, the rema: arms and over : 3 0 y e a r s . H i s 3- Case 3 (Den They were scab 10 years ago. C ape 4 (Ej r four kcratotic h skin over tins : but Dr. Scot: s {rolEi ail Cut!'1A ' lading! (Jcrn'.Atr. The latter wen. obs t r u c t i o n ot They were not th e paraffin \v. bail developed ' this case as iliu to he enp Ur. e A!! m e n it!,in i r m a h ; Re in this way. in a r e a s nj oil w o r k e r s c lim it irs. The cry:' in tile para:: removed ir, r is allowed i scab or pat paraffin wo: lab o re r' mo- existing der: Or. the i experienced : been brur.g. large mcasu: that date tl TUDIES Piting intliad. ExperiuuJ will be il were noted (port of 65 i'h sl'.ale-oil ;>ultant for him at the !Measure of ef chemist, plant. He at 1600 to ie oil. The `cessed to Age.- The mre detail t. 18. 1950. -t-Graduate :t> from the liie Scottish nnatose of die System ell. Eighth industry in cottish Oils, S M I T H --l i K i r i S l l A M ) 11( ' / V i l . Y I l ' M O K I' ROKi.LMs 24.i During the past 3U years the mtmher of employees engaged in ptirtitVin process work has remained ahout the same, 40 to 45. Hr. Scott stated that in 1'dO, when he made his first survey of the plant. 4.''- of the men in the paraffin works had dermatitis. At present, only 7.5% are so affected, representing a total of three cases, which i saw together with a fourth case, that of a man who had retired. All had been exposed for 20 years or more: ' Case 1 (Dermatitis Erythematosa 1.--The forearms were covered with dull-red splotches of varying size and shape, which blanched on pressure. This man had been employed for 27 years. The erythema had appeared over the past six months. Case 2 (Dermatitis Erythematosa).--This was a more advanced stage of the condition seen in Case 1. 1 lie splotches were raised and had a brownish tint. Between them were many white scars, the remains of earlier lesions. This man also had oil folliculitis, the hair follicles on the arms and ove- the knees standing out prominently as black points. Ele had been employed for 30 years. His dermatitis had begun 20 years ago. Case 3 (Dermatitis Papulare).-- Brownish purple papules were scattered over the forearms. They were scaly and firm. The man had been employed for 24 years.. Lesions began to appear 10 years ago. ' C a se 4 (Epithelioma).--Two cancers had been removed from this man's forearms. He had four keratotic horns on his hands and a suspiciously firm mound in the skin at the wrist. The skin over this mound did not seem remarkable, and the lesion had no papillomatous features, but Dr. Scott said he had found cancerous downgrowths in a biopsy specimen of such a lesion from an earlier patient. On the anterior surface of the legs and on the forearms there was a fading dermatitis erythematosa. On both the legs and the arms were many "paraffin warts." The latter were raised, conical, red with a black head in the top. They were said to be due to obstruction of sebaceous ducts with paraffin, and to disappear readily when this was expressed. They were not associated with subsequent neoplastic change. This man had been employed in the paramn works for 30 years and had then retired. His dermatitis and subsequent skin tumors had developed wholly in the period of three years after he left the works. Dr. Scott emphasized this case as illustrating the need to follow exposed personnel even though they may have ceased to be employed in a hazardous job. Ali men at the works are examined at three-month intervals, and anv skin abnormalities are recorded on charts of the anterior and posterior body surfaces. In this way, I)r. Scott has been able to show that in paraffin workers tumors arise in areas of skin that have been the site of preexisting dermatitis. Bv contrast, in 011 workers epitheliomas usually arise without preexisting dermatitis, even on hands or arm.-. The records disclosed no association between injuries and localization of tumors. The erythematous dermatitis mav occur after onlv a few clavs of employment in the paraffin works. It usually responds to treatment. If it persists, the man is removed from the works, the dermatitis then usually clearing up. If the dermatitis is allowed to become chronic, with the skin becoming indurated and covered with scaly or papular lesions, danger of cancer arises. In contrast to the tendency for paraffin workers cancer to occur on the forearms, oil workers, retortmen. and laborers more commonly incur scrotal cancer, which arises without observable pre existing dermatitis. On the basis of the greatly decreased incidence of dermatitis and skin tumors experienced among employees in recent years Dr. Scott felt that these problems, had been brought under satisfactory control in the Scottish shale-oil industry. In the case of the paraffin workers, he felt this improvement had been made possible in large measure by a change in the type of press, a change made in 1935. Prior to that date the crude paraffin scale from a low-pressure pressing operation was 2-1-1 ix n r s T k iA L n v c n ix n .ixi> o c c r r . r iio x M:.l1! Ci X /: shoveled onto canvas sheets, on which it was spread out into a shallow aver by the workers hare hands. 1he sheets, thus loaded, were piled one on top <n the other, by hand, into a press to squeeze out the oil, after which the paraffin was flaked oft by hand. The whole process thus involved very intimate exposure of the skin ol the lorearms, hut the legs and the body were protected b\ heaw canvas wrap pings and aprons, respectively.' These conditions doubtless accounted for the common occurrence of skin tumors on the arms of paraffin workers and the relative rarity of scrotal cancers. Leather or rubber shields had been experimented with, to protect leys and body, hut discarded in favor of canvas, which was found in practice to he more effective in preventing dermatitis. The canvas is of the same quality and thickness as that ordinarily used in wax presses i 16 oz. per square yard; 54 gm. per square meter). In 1935. the procedure just described was replaced by high-pressure filter presses into which the oil is fed. chilled, and pressed without handling until the press is opened. The pressmen wear canvas aprons. 1 saw these new presses and found them to lie very similar to those in use in American wax works. Since skin and scrotal cancers have occurred in pressmen operating such machines in America, it did not seem likely that the change in equipment could, account entirely for the very remarkable decrease in skin disorders described In Dr. Scott, though, it must have been a very major step in that direction. Other factors have also to be considered. Among these other factors has been the installation oi shower baths and washing facilities. Ordinary neutral soap is used. The workers have cooperated in the use of these facilities, which include means for laundering their own work clothes, which they leave at the plant in lockers instead of wearing them home. For laundering clothes, a detergent ("by-prox") is used and has been found satisfactory in remov ing oily matter. It is made by Scottish Oils, Ltd., Mid-Cakler, Scotland, and is a sodium alkyl sulfate (a sulfated oil. not a sulfonated oil ). A further procedure has been adopted based on experiments by the Tworts." who found that mice painted with carcinogenic oiks yielded fewer tumors if their skins were rubbed with hvdnnts wool fat (lanolin ) prior to painting. At the 1'umpherslon works, each man is issued a weekly ration of y2 lb. (226.5 gm.) of olive oil containing 250 hvdrous wool fat. Peanut oil had been tested for this purpose lmt discarded as not having enough, "cling": i. e,, it remained on the skin less well than olive oil. Castor oil had been used earlier, without hydrous wool fat. and given up for reasons not stated. At present, therefore, the practice is for the men to rub their arms and hands well each morning with, the mixture of 2 5 0 hydrous wool fat in olive oil. Aside front any merit which this procedure may have in protecting the skin, it is said to facili tate the removing ot oil from the skin bv subsequent washing with ordinary soan and water. Barrier creams ( "roza'lex" and "esoban" ) have also proved satisfactory, ll dermatitis develops, it is treated with a medicated cream,-' This alleviates the o. 1 wort. C. C... and Twort, J. M.: Studien nber Krehscntstehung, Zischr. Kreh.-inr-ch. 3 2 : 504, 1930. Twort, J. M,, and Lyth, R . : The Prophylactic Effect of a Colloid Material on the Skins oi Mice Painted with \ ariutis Types of Carcinogenic Agent-, I. Hyp. 43:252-255. 1944. ' ` ' ' 4. I his cream is made of the following ingredients: stearic acid. 15',7 ; hvdrous wool at. 1090; white wax, 8A : liquid petrolatum. 1(>.5C ; distilled water, 48)7; bela-phenylethy! iodide, l c/( : titanium dioxide. 0.5)7 : nionoethannlanune, 2-aminncthanol. 0.8)7 ; chlurocresol, 0.2c/c- It is marketed by Calmic Ltd., Crewe, England. / V/: allow layer by : on top of the iffin was flaked are of the skin . canvas wrap- 'tintecl for the and the relative rimented with, ' was found in is of the same it square yard; '.as replaced by :.cessed without is. I saw these \merican wax aperating such uipment could 1 s described by rection. Other lis and washing ated in the use . clothes, which bor laundering lory in remov- aland, and is a procedure has .1 mice painted 1with hydrous i man is issued Irous wool fat. having enough - t oil had been not stated. At uni hands well il. Aside from said to facili- ordinary soap ed satisfactory. - alleviates the SMITH--BRITISH AS1) ,-A'KOI'HAS I l A l v K J'kOHUiMS 243 asuteness ol the disease, and Dr. Scott Imds that the acute type clears up readily. Once wartimes or scalmcss develop:-, it will not clear up but can be kept under control by any good dermatitis cream. In addition to the change in equipment and the measures just described for protecting the skill, potential employees are screened with the aim ol jacking men with swarthy skins, as these do not appear as susceptible to oil irritation. Men with auburn hair and men who freckle readily or who have preexisting skin disease, especially psoriasis, are not hired as pressmen. Lastly, 1 could not fail to note the excellent relationships between management, labor, and medical officer. 1 heir mutual interest and cooperation have no doubt been a major factor in bringing the situation under control. The friendly confidence apparent in the relations between the employees and Dr. Scott is a warm tribute to this kindly physician and to the officials of the company, who have together ablv met a classic task oi industrial medicine, ft is a pleasure to acknowledge the cour tesy and advice o! Mr. Alan Anderson, the works manager. ^ r - f'cott showed me an excellent series oi lantern slides illustrating gross and microscopic features oi the dermatitis and the tumors here discussed. The Cancer Prevention Committee lias obtained reproductions of these slides, which are avail able for loan to oil companies wishing to use them for instruction of medical personnel. In London. 1 visited Dr. S. A. Henry, former medical inspector of factories, who lias analyzed 4.624 cases of skin tumors reported as of occupational origin since 1920 under the British Workmen's Compensation Act. provisions of which, are described in Dr. Henry's reports/ Mule spinners in the cotton textile industry contributed 1,40/ of the above total of cases. I he hazard in this occupation has been traced to the use oi carcinogenic oils, notably those containing shale oil. to lubricate the spindles. Dr. Henry s published analyses show a marked decrease of the skin cancers attributed to shale or mineral oils in recent years. Pie credited this improvement to increasing adoption of noncarcinogenic spindle oils and to the fitting of telt washers onto the mules to prevent oil spray. The shortest time elapsmg from onset of work to manifestation of cancer in cases attributed to shale or mineral oil was lour vears. but the maximum number oi cases was reqiorted alter 50 to o4 years' exposure. Further comment on this subject is contained in the last section of mv report. Extensive experimental studies on the carcinogenicity of shale and mineral oil are contained in the monumental works of the Tworts and their associates. Dr. C. C. T wort has now retired from work with oils, but lie generously supplied; at my request a collection of his papers on the subject. A bibliography of this valuable collection, comprising some 40 titles, can be obtained from the Cancer Prevention Committee. hr. Krebsiorsch. Slid Materia! on ;iyg. 43:252-255, ydrous wool fat, inylethvl iodide, ' esol, 0.2%. It is II. PETROLEUM Through the courtesy of Proi. John R. Squire, I had the opportunity of becom ing acquainted with the studies going forward at Birmingham University in col laboration with the Committee on Carcinogenic Action of Mmoral Oils appointed a. Henry, S. A.: (a) Occupational Cutaneous Cancer Attributable to Certain Chemicals in Industry,Jlritish M. Hull. 4:380-401, 1047 ; (/>) Cutaneous Cancer in Relation to Occupation, Ann. F y Coll. Surgeons England 7:425-45-1, 1950. 246 lx n rsih 'l.ii. nYc.inxa ,-ixn - >ccn \rn o .xa l m iu jic im ; 1)_Vthe Medical Research Council with the support of the British petroleum industry. In the cancer research laboratories of the i riivcTsitv various oils tire being tested on the skins ot animals by Dr. D. L. \ \ oudnouse, and epidemiological studies are juir.sued by Dr. C. X. D. (. ruickshank and Dr. J. lb Bull under the direction of I'rof. Squire in the Medical Research Council Industrial Medicine Research Unit in the nearby Birmingham Accident Hospital.' Oil samples for experimental study are being prepared in the department of chemical engineering at Birmingham Uni versity under the direction of Prof. F. H. Garner. These British studies, like those conducted by ourselves0 at New \ ork University, are concerned with oils derived from petroleum rather than from oil shale. Important ditierences emerged between the studies in progress in England and those in New York, for the British are test ing lubricating oils where cracking is avoided whereas we have been concerned primarily with cracked oils designed for other purposes. Prof. Garner stated that British lubricating oils are made bv subjecting crude oil in vacuo to distillation at a temperature not over 350 C. This is the actual tern- Crude Oi 1 dewoung Extract solvent exttOLtior. <SC2) Reffmote Wn.te 0-i j fuming rUSO^ j________ Detergents, etc. (in HjSO^ layer) Outline of a petroleum fractionation. perature in vacuo, not after conversion to atmospheric pressure. The vacuum is about 20 mm., hence this temperature would correspond to about 550 C. (1,000 F.) at atmospheric pressure. Prof. Garner stated that in practice the oil is exposed to this temperature only for a matter of minutes and that the refineries try to avoid cracking by keeping the time of exposure down as much: as possible and trving to keep the in vacuo temperature below 300 C. The accompanying outline mav serve for orientation. The SO? extract t Edelennu process ) removes the aromatics, which are unde sirable m lubricating oils because they oxidize easily and are then deposited as sludge. The extracts are said to be used to some extent in cutting oils and in the rubber industry. The raffinate (oil left after SCk extraction) is used for lubricat ing purposes in the engineering industry. When raffinate is treated with fuming6 6. Smith, \V. E . : Sunderland. D. A., and Sugiura. K . : Experimental Analysis of the Car cinogenic Activity of Certain Petroleum Products. A. M. A. Arch. Indust. Hyg. 4:299-314 (Oct.) 1951. Sunderland, D. A.; Smith, \Y. E.. and Sugiura, K . : The Pathology and Growth Behavior of Experimental Tumors Induced bv Certain Petroleum Products, Cancer 4:1232-1245 (Nov.) 1951. sulfuric arid. Cotton lextbo cancer. Bioiogica. degrees of ca Six finished s; of carcinogen:group of 50 u statistical ana" Dr. Woodhov mice could be a sample for i potent the tie ferent samples concurrently. The Iiritis" by chemical . The earlier v, reviewed by 1 tivity per >e : refractive un marv ot them Auk! stated d ingiess as no 1 lie preset:: ; O ils is that : aside from tk lit the matte: carcinogenic, care; n o g e '.r.cu at the Mam., (lata snppheb: T h e qt'.e-' experimental states that it less hard m: or dissolve k- substances : arise less or. rather than :: 7. W oM T : Extract-, j. Id- 8. Irwin, j. IV: ipertK- "t ! 9. An!.!. S 9a. Fischer. Properties ; to Caro:,, gei. industry, ii" tested udies are rection of :irch Unit ntal study :ham Uni like those ils derived d between h are testconcerned ting crude ictual tem- i vacuum is 1,000 F.) exposed to y to avoid 1 trying to may serve are undeposited as and in the t lubricatith fuming - of the Car e. 4:299-314 and Growth 4 :1 2 3 2 -1 2 4 5 S M I T H --A R T U S H A S H H C h O n U X T I'M ON I'K OH L T M S 2-47 sulfuric acid, white oil is obtained, and this is now used to lubricate spindles in the cotton textile industry in place of the shale oil long associated with mule spinners' cancer. Biological tests carried out on mice by I)r. W'oodhouse demonstrated varying degrees of carcinogenicity in several lube distillates, residues, and one extract.' Six finished spindle oils (not white oils) were tested, and all exhibited some degree of carcinogenicity for mice. In 1946 tests were conducted with 10 oils, each on a group of 50 mice (25 males, 25 females). In 1947 these tests were repeated. A statistical analysis of the results was made by Dr. J. O. Irwin and is appended to Dr. Woodhouse's paper/ The two sets of tests demonstrated that groups of 50 mice could be counted on to give satisfactory impressions of the carcinogenicity of a sample for ordinary purposes. That is, no sample found weak in one year proved potent the next, or vice versa. If a close comparison of the carcinogenicity of dif ferent samples with attention to small differences is desired, the}- should be tested concurrently.. The British group is exploring means for evaluating the carcinogenicity of oils by chemical or physical methods rather than by time-consuming biological tests. The earlier work on this subject by C. C. and J. M. Twort and their colleagues was reviewed by Irwin and Goodman.' who presented arguments to show that refractivity per se is as good a measure of carcinogenicity as the study ot the change in refractive index following imraperitoneal injection (set Paragraph 9 in the sum mary of their paper). The matter was turther discussed by S. J. M. Auld." Col. Auld stated that certain blending procedures render refractive-index studies mean ingless as measures of carcinogenicity and presented data illustrating this point. The present position of the British Committee on Carcinogenic Action of Mineral Oils is that there is no reliable means for estimating the carcinogenicity of oils aside from the biologic test. Perhaps an exception to this statement mat- be made in the matter of color in the sense that white oil has never been found to be carcinogenic. Addendum: Chemical and physical method;- fur estimating the carcinogenicity of high-builing petroleum products have recently been developed at the Standard Oil Development Company. Linden. X. J.. utilizing biologic test data supplied bv our laboratory at Xew \ ork University."" The question of a solvent less volatile titan acetone or benzene often arises in experimental cancer work. Dr. W'oodhouse has found toluene satisiactory. Pie states that it is no more irritating to mouse skin than acetone or benzene and is less hard on the animal as a whole than is benzene. He has used toluene to dilute or dissolve heavy oils or tars with satisfactory results as regards skin tests of these substances for carcinogenicity. Dr. Woodhouse found, as have other.-, that tumors arise less quickly and in less number when a carcinogen is applied in white oil rather than in acetone and has obtained quantitative results in relation to the chiu-789 7. Woodhouse, D. L . : The Carcinogenic Activity of Some Petroleum Fractions and Extracts, J. Hyg. 47:121-134, 1950. 8. Irwin, J. O., and Goodman, X.: Statistical Treatment of Measurements of Carcinogenic Properties of Tars and Mineral Oils. J. Hyg. 44:362-420, 1946. 9. Auld, S. J. M.: Environmental Cancer and Petroleum, J. Inst. Petroleum 36:244, 1950. 9a. Fischer, H. G. M.; Priestley. \V., Jr.: Kby. L. T.: \ \ anless. G. G., and Kenner, J,, Jr.: Properties of High-Boiling Petroleum Products: Physical and Chemical Properties as Related to Carcinogenic Activity, A. M. A. Arch. Indust. Hyg. 4:315-324 (Oct.) 1951. 248 X I H ' S ' J h'L U . // J '6 7 / ; . \ 7 : . 1 X 1 ' f't. (7 7 ' . / / / ( >.Y. ,7. MEHIL IXl i timi used. Mite and ilea miestnlinn- jiresent serious problems in experiments on tlie mouse skin, and investigators o:ten hesitate to use insecticides tor fear oi intro ducing unknown iactors into their ex]icriments. Dr. Wnodhuuse uses benzene !a x,ichloride foi control ot these pests. mixing a little ot tlie powder into the saw dust used tor bedding. Tests conducted by himself and Prof. Orr at Birmingham have shown that this material does nut produce cutaneous injure, skin tumors, or pulmonary adenomas in mice. The preparation they use contains 0.1 c/c. by weight benzene hexachloride mixed with talc.10 . Dr- ^ oodhouse has studied means for removing carcinogenic oils from the skin of mice, using ultraviolet fluorescence as the criterion. He found that all fluores cence could he removed iroin the skin by wiping the painted area with cotton soaked m white oil. then wiping tlie white oil off with dry cotton. Sultonated castor oil proved less eiTective for this purpose. White oil did not injure the skin of mice, even when applied twice a week for 25 weeks. In our hands this procedure, has not completely removed fluorescence from mouse skins painted with high-boiling cata- lvtically cracked oil. & _ I next visited Dr. C. X. D. Cruickshank and Dr. J. P. Pull at the Birmingham Accident Hospital. Dr. Cruickshank recently published an experimental study of various skill cleansers, concluding that oils could best he removed from the human skin by a mixture of equal parts of soap powder and fine wood flour.11 He has subsequently found white oil to be more efficient than tlie mixture of soap and wood flour. His experiments showed that barrier creams were of little value as protection against oil, but he felt that an emollient cream to minimize the deleterious etiects of frequent skin cleansing was useful. A practical discussion of skin cleaning m industry with special reference to oil is contained in another paper bv Dr. CruicD shank,12134which states that during the years 1943 to 1946 approximatelv 9.80.) cases oi industrial dermatitis (all causes) were certified annually in Britain with an estimated annual loss ot 98,000 man-weeks. It is interesting to note that in the two years 1943 and 1944 in Xew York State the claims made for industrial dermatoses totaled 4,135, ot which 890, or 21.591-, were for dermatoses attributed to oil or grease exposures. Hall of the latter group involved cutting oils.11 The Birmingham workers have also been engaged in statistical studies of the type.- and number of industrial dermatoses notified in Britain.11 Dr. Cruickshank gave me a striking demonstration ot Ins method of removing a lubricating oil from the human skin. He painted this oi! on his arm. which came to fluoresce brilliantly in ultraviolet rays. After washing with the mixture of soap and wood flour and water, the diffuse fluorescence was seen to have been removed, but the hair follicles in the oiled area shone forth brilliantly as fluorescent snots. 10. It is marketed under tlie name "lorcxane" by the Pharmaceutical Division of Imperial Chemical Industries, Manchester, England. Another preparation of "orexanc," i f f in miscible oil. is also available commercially and is used at Birmingham as a spray to control flics on walls and in boxes. . ]1- Cruickshank, C. X. D . : The Evaluation of Skin Cleansers ami Protective Creams for Workmen Exposed to Mineral Oil. British 1. Indust. Med. 5:204-212. 1948. 12. Cruickshank, C. X. D. : Industrial Skin Disease. Xursing Times, Inly. 940. 13. Shapiro, H . : Cutting Oil Dermatoses, Month. Rev., Xew York State Dent, of Labor 1 29:5-8 (Feb.) 1950. ' 14. A review of occupational skin diseases hv Squire, Cruickshank. and Toplev recently appeared in the British. Medical Bulletin (7:28-41, 1950). ' ' i H e i- with ceno Dr. i wash i of i r i : of w;. D. skin < oil w' tunin were secth of wl cheiu Finn but i v a n 1.' acid. <ieue: ahuu' crysu has : hand arms gens tHHi lw ;; in i: wax and cans in a <!UC' Fas; 15 the v Man SM IT H --B R IT ISH .-IS'D EVR O P E A S TV MOR PRO BLEM S 24 q ments on r of intro - benzene the sawnningham umors, or by weight He then covered his arm again with the lubricating oil. but this time rubbed it oft with cotton soaked in a colorless technical grade of white oil. Almost all the fluores cence was thus removed. on!v a little remaining in a very tew scattered Hair tolliclcs. Ur. Cruickshank stated that lie had not found dermatitis to result in human skin washed repeatedly with white oil. provided the skin was healthy to start with. Crises of irritation occurred when the oil was applied under dressings, further discussion of ways to protect the skin against oils is contained in my section on "Shale Oil." Dr. Cruickshank and Prof. Squire have described warts that occurred on the ni the skin .11 fluoresmn soaked castor oil n of mice, ire lias not ding cata- skin of 33% of a group of 138 machine-tool operators exposed to sprays of a cutting oil which they found capable of inducing skin tumors in animals.1'' I had an oppor tunity to examine many excellent photographs of these men. Some of the lesionwere flat, white keratoses; others were raised, rugose, and pigmented. Histological sections showed the latter to be papillomas. One man had a scrotal cancer, sections of which I saw. Photographs of his arms showed hah a dozen small papillomas. Prof. I. W. Cook, at the University of Glasgow, is attempting to identify the chemical nature of the carcinogens in the petroleum oils under biologic test at rmingham Birmingham. Prof. Cook was awav from Glasgow when 1 visited his laboratory, ,1 study of but the work was described to me by his assi-tant. Dr. \\ . Carruther-. By high- die human vacuum distillation, chromatography on alumina, and purification with picric ! He has acid, they have isolated a chrvsene with a long aliphatic side chain. I heir A. soap and general procedure is to extract the oils with sul'ur dioxide, run the extracts through value as alumina columns, and elute with petroleum benzin. 7 hey have thus obtained four leieterious crystalline compounds, as vet unidentified, of which two are aromatic, (duly one . cleansing has been obtained in sufficient quantity for biologic test, but results are not yet at >r. Cruick- hand. '.800 cases Thev have failed to find benzpvrene. The method oi search was to extract the .i with an aromatics with sulfuric acid, regenerate the hydrocarbons, and examine by fluores in the two cence spectroscope. Dr. 1. Hieger, of the Chester Beatty Institute, London, was iermatoses also said to have searched unsuccessfully for benzpyrene in lube oils found carcino i to oil or genic at Birmingham. I mat' note here that a very simple procedure n>r the detec rmingham tion of benzpvrene was demonstrated to me by Mr. Robert \\ aller m Sir Lrnest number of Kennawav's lahoratorv m London. An account ot this method will appear shortly in the British Journal of Cancer. All parties agreed that absorption spectroscopy removing hich came was useless as a means of identifving compounds in complex mixtures, such, as oils, and emphasized the need iter fluorescence spectroscopy. ire of soap u removed, cent spots. III. ASBESTOS The 1947 report of the Chief Inspector of Factories Ji; noted the presence of cancer of the lungs or the pleura in 31 t 13.2% ) of 235 cases o: ashe.-tosis recorded "i Imperial in the 23 years from 1424 through 1940. These figures stimulated interest m the in miscible lies on walls question of whether lung cancer is an occupational hazard in the asbestos industry, and, if so. which phases of the industry and what working conditions present such Creams for a hazard. The data cited above were prepared by the Senior Medical Inspector oi Factories, Dr. E. R. A. Mercwether. whom 1 visited.156 t. of Labor ley recently 15. Cruickshank, C. X. D., and Squire, J. R. : Skin Cancer in the Engineering Industry from the Use of Mineral Oil, Brit. J. Indust. Med. 7:1-11, 1950. 16. Annual Report of the Chief In-pector of Factories for the Year 194", London, His Majesty's Stationery Office, 1948, pp. 79 to 81. (Price 3 shillings.) 3a iff-.,-4 .'I 250 I MA S R I A L HYGIEM: A.\I> OCCl 'R A T IO. XA!. MJ i DJ C I X L Dr. Merewether reterml to the governmental report pnhlislicd in 1930 |>y him>elt and (... \\ . Price.1'" This report showed that ashestosis develci])ed in 80% 0f men employed 20 or more years m the industry-'' and that in various groups of " o r -eis the percentage in which ashestosis developed varied directly with the desti n e s of the process in which the groups were engaged.-" These findings led to the adoption oi laws requiring ventilation of asbestos work rooms in Great Britain .Asbestos Industry Regulations. 1931). Detailed specifications for safety equip ment are contained in Factory Orders. 1944. It should be noted that there is no mining of asbestos m England. Hence, the British figures refer only to individuals engaged m weaving or other manufacturing or handling operations. A first problem was whether the apparent association of lung cancer and asbes- tosis means merely that workmen's compensation procedures funneled all chest diseases into one group. This possibility cannot be supported, however, for no such high incidence of lung cancer has been found in cases of silicosis, which are likewise reported to and reviewed by the Pneumoconiosis Board. Cancer of the haws Zn? was noted in only 91 (1.32%) of 6,884 cases of silicosis recorded from 1' '30 through 19464" I he incidence oi cancer was thus 10 times greater in asbes- tutic lungs than m silicotic lungs. Data on the average age at death in this silicotic group were not given, but the same report listed a series of 1,037 silicotics who c eel at an average age of 58.2 years, compared with a group of 160 asbestotics who med at an average age of 47.5 years. Therefore, the difference in cancer incidence m the two diseases could not be attributed to death of silicotics before they reached t| e . cancer a4e >n tact, the silicotics would appear to have had greater oppor tunity by a full decade to yield cancers. Similarly, the average duration of e n j o y ment m these two groups could not account for the difference: 34.3 tears for the silicotics against 14.9 years for the asbestotics. ' pun: deaf i I f / thus. f 8.3' gr-'--" 2.sl >(' >' I 10 I to Ij incuit sex r. h witiK cun: - A measure o! the rate at which lung cancer occurs in the general population of l i g and md Males can be found m the Registrar General's Statistical Review , , Employing the data given on pages 3 and 145 of the Review, one can i ca.culate that 1.36% oi all deaths in the three years from 1943 to 1945 were reported 1* as due to cancer of the lung, the bronchus, or the pleura. It is of interest to n,,te tput the percentage ot deaths attributed to lung cancer m the general population \ is almost icemica! with the ngure oi 1.32% for the finding of lung cancer m a I large group oi silicotic lungs. & 1 uesen ti;:> t comi;. in hi- - Documentation oi the cases of coexistent lung cancer and ashestosis became mv 1 T. next endeavor, hor this purpose, I visited Dr. S. Roodhouse Glovne at the Insti 1 tods atusOteesttoosrisBaorecalwe.lMl ekdnicoiwnen.-m FOoxrfomrdan. y Dyre.arsGlhoeynhea'ss rsetcuediiveesd olfuntghse fopratrheov!i,,eww oonf j matters oi compensation. Dr. Glovne generously gave me permission to cite the ? data m Table 1, which ne assembled from lungs that he personally examined ,r the 1. gross and microscopically. It is to be hoped that a full account of them will be i 1 tltncix canee; hronc: IOUHm K- 7. fa) Merewether, E. R. A,, and Price, C. W . : Report on Effects of Asbestos Dus, on the Vi ungs and Dust Suppression ,n the Asbestos Industry. London, His Majesty's Stationery Office j toll . II.. and D2-1M,, 19o3-19.,4>; , H/,,y",,hlcd.. T,,0Xi1C00. 1'Ta1b2l:e1137:' 1(<rJ)3 'ibaimd.I, ipn. T4u. bTeradbele 7. =69-81. 1W- s ao^uQ-G10>? e-'-S - : The M rbkl Anatom-v and Histology of Ashestosis, Tubercle 14-44S4M ; rtvciw A. Sue -Xew York, Oxiord Lmversity Press, 1938, pinp. S2"25-244. "nd - t e d bv Lanza A 'i '' C u TVHL 1 W i bv him- uroups of he dustigs led to ;it Britain riv equiphere is no ndividuals and asbesi all chest r, for no which are the lungs rded from in ashes - silicotic tics who "tics who incidence v reached v r opporf employrs for the nation of .1 Review . one can reported -t to note .i qmlation ncer in a came my the Instihologv of review on " cite the ;ed in the n will he . mst on the aery Office, 0.9-81, 109- 14:445-451, mza, A. J., S M IT H --liK lT lS H A S 1> L C K U P L A S T l 'M u k PHOHUIMS 251 published from a manuscript that was in preparation at the time of his recent death.16 In addition to the material ot Table 1, IJr. Glovne also examined the lungs of 1(>9 persons without pneumoconiosis hut employed m the same set ot industries as those included in 1able 1. .Among these, he tound 14 who had primarv lung cancer (8.39c ) The lungs of 11 asbestos workers who had no ashestosis (either in the gross or microscopically ) were negative for carcinoma. The 17 cases of cancer in asbestotic lungs t fable 1) were about equally distributed between men and women (10 men. 7 women], whereas in the normal population in England the ratio is said to be 4 men to every woman with cancer of the lungs. In addition to the higher incidence of cancer in asbestotic lungs. Dr. Glovne felt that this diffrence in the sex ratio afforded evidence for an occupational factor. It will be apparent that the lung cancer rate of 8.37c found in the 169 individuals J without pneumoconiosis and the rates of 5.1 to 8.97c in the groups with pneumo conioses other titan ashestosis are much higher than the rate of \.3(>c/c estimated for the general population on the basis of death certificates and the rate of 1.327c tound from pathological examination of the large group of silicotics previously T able 1.-- Incidence of Primary Lung Cancer in Groups scilh 1 (irions I x p c s of Pneumoconiosis Data (>f S. Rvodhousc Glovurt Per-ons will) Pneumot omijiatiorial (irouji Total .VlHUDt'j Number with Primarv Lung' t 'nnerr IVrret; t :t>'. with Pr.marv Lung Luncer i Potterv workers .................................................. 1!' fi.t. Asbestos worker- .................................................... ............... ]'! 17 U i; described. It is thus probable that the higher rates reflect closer studv. Despite ' this elevation of the base line for comparison, the rate in the ashestosis group continued to stand out. Dr. Glovne stated that of the total number of lung cancers in his series. 7.5r/c were discovered only on microscopic examination. These were scattered through the various groups. ] The type of cancer-" and the degree of ashestosis in the 17 cases of the ashes- j tosis group are given in Table 2. Only one individual (M. S.) had evidence of tuberculosis. In the 922 cases comprising the whole of the pneumoconiosis group (Table 1 209e showed tuberculosis. Dr. Glovne made a special search fur pre- ( cancerous changes in asbestotic lungs and did not detect am. Desquamation of j bronchial epithelium was occasionally seen, but squamous cell metaplasia was not i found save in the cancers themselves. It will be noted from Table 2 that the degree 19. A brief posthumous publication has appeared (Glovne. S. K. : Pneumoconiosis: A His tological Survey of Necropsy Material in 1.205 Cases. Lancet 1:810-813. 1951). 20. Through the courtesy of Ur. K. F. W. Hinson, of the London Chest Hospital, we have received lobes from six lungs of Dr. Gloyne's series. T his material was examined by Dr. Douglas A. Sunderland, of Memorial Hospital, New 3 ork. 1wo eases (C. \ \ . and 1. \ \ . ) classifie'd as squamous cell cancer by Dr. Glovne were interpreted as terminal bronchiolar ("alveolar cell") carcinoma by Dr. Sunderland 252 ixin'S r ia l !m a u x h xxn occ rr.mux.ii. u iu n a x n of asbestosis in the group of cancerous lung.-, was recorded as "moderate1' or "extensive" in even' case except one, where it was "mild.'' The estimation of the I degree of asbestosis was made in every instance by the same observer (Dr. Glovne). The 17 cases of coexistent lung cancer and asbestosis studied hv Dr. Gloyne were assembled over a period of 20 years (1929 to 1949). All had their exposure to asbestos prior to 1932, the year modern exhaust ventilation devices were adopted in conformance with government regulations. The majority were emploved at a plant handling Rhodesian blue and South African (also blue) asbestos. Both these types are more brittle than Canadian white asbestos, hence give rise to more dust. At least one patient (J. 1.), however, was stated to have been exposed only to Canadian white asbestos. I next visited Prof. E. J. King at the British Post-Graduate Medical School in London, where 1 had the opportunity to examine protocols relating to the lungs T able 2.--Pathological Findings in 10 Men and 7 U 'onien with Asbestosis and Lung Cancer (Data of S. Roadhouse Gloyne i Patient (Mali1) A. G........ A. \V....... P . B ........ J . G ......... J. 1.......... G. M....... E. T ....... J. W ....... C. W...... J . P ......... (Fcmale.O U S ...... E. W ....... m. e ...... E. O....... M S ........ Le. s.... R. M....... Dpi: reo of Asbestosis Tyj'P oi Cancer Extensive "O at Cell" Extendw " O a t ('el! Motion! re Kijuainoi:* ('ell 1 Moderate Sfji:it :n t>n> i VI) I Minienti*1 S.juainun^ ('eli I Moderate S<iD:ni:oi:v ( 'ell 1 Modera it- Ceil Mollerai' >v|;;an:oD- ( 'ell 1 Moderale Soliamoli* ('ell I Mii " O a l ( 'ell" i Extensive Sijtianiuii* ( eli n Exleii>ive Sqt:an:oi;v Cell f Mode! lile Squanii-ws Ceil Mo. `era u- " d a l Celi" a Moderale "Oal Cel!" f Modern le Adeiioea rcii'oiiia 1 of 11 individuals who had been employed in a plant using Canadian white asbestos. The pathological descriptions were made by Dr. C. Y. Harrison. Varying degrees of asbestosis were noted in S oi these 11 lungs; there were 3 cancers, all among the 8 asbestotic lungs. An "oat cell" cancer was tunnel in lungi o! one patient (male) with extensive asbestosis. Anaplastic carcinomas were described in two patients (males), in one of whom the degree of asbestosis was moderate; in the other the asbestosis was minimal. The asbestosis ranged from extensive to mod erate in the 5 remaining patients in whom this disease was not complicated hv cancer. Combining the data oi Dr. Glovne and Dr. Harrison, one buds that in 20 cases of coexistent lung cancer and asbestosis. the degree of asbestosis was "extensive" in 5, "moderate" in 13, and "mild" or "minimal" in 2. The cancer was squamous cell in 11. "oat cell in 6, anaplastic in 2. and adenocarcinoma in 1. There was no correlation between type of cancer and degree of asbestosis. I next visited Dr. Hubert Wyers. the medical officer for a companv in England engaged in manufacturing asbestos products from blue asbestos mined in Rhodesia or South A He stated major state, asbestosis : exhaust vc. involving a in regard u of prevent!', the number individual c ring after ' chronic. lr. found in 17 diagnoses < All of i 1932. Acc Dr. Darri- M erew ethc reported m that onlv i betw een P " norm al" ; a s b e s t o - ir. w ith coex; u n d er con, u p th e to;; tories lor ; to locate a it \va> n a t u r e o! ; Ci numi m a; place uub existed in sudi a Ita, that a iihu cases of atheir emp! which turn but the law and asbe.-t least in pn delayed, ap Pro;. K COllli'ses. ; 21. Wvei S M I T H --HR m s n i) T .n s>i'H A S T I'M Ok P R u T L TM s 253 rate" or >n of the Gloyne). Gloyne exposure e adopted >yed at a 1loth these .ore dust, d only to or South Africa. Dr Wvers is the author of a valuable clinical study of ashestosis. He stated that ashestosis w;is recognized in 1900 and that the industry grew to major stature in the war of 1914-1918. Dr. Wyers has seen only two deaths from ashestosis in people who started to work in the industry after 1932, the year when exhaust ventilation devices were installed. In contrast, he had seen 115 deaths involving ashestosis in persons employed before 1932. He feels that the regulations in regard to safety conditions in the asbestos industry are therefore a great triumph of preventive medicine. The diminution in the severity of the disease in terms of the number of persons affected is further borne out by lessened severity in the individual cases. Prior to 1932 the disease was acute, with deaths sometimes occur ring after two years of exposure. The disease as it is now seen is much more School in chronic. In the 117 cases of ashestosis seen by Dr. Wyers primary lung cancer was ihe lungs found in 17. Dr. Gloyne examined the lungs in these 17 cases, and his pathological jt ;.. . diagnoses of the tumors have been given above. :ag Cancer ' All of the 17 individuals with ashestosis and lung cancer were exposed before 1932. According to Dr. Merewether, the additional 3 cancer patients studied by Dr. Harrison were likewise exposed before 1932. 1 specifically inquired of Dr. Merewether whether any cases of coexistent lung cancer and ashestosis had been reported in individuals whose exposure had taken place only since 1932. He stated i-v that onlv one such, case has been reported : that of a man employed in the industry between 1935 and 1945. This single case might well be expected as part of the ``normal" incidence of lung cancer in any group as large as that employed in the asbestos industry. In summary, then. I was able to find some information on a total of 21 persons with coexistent lung cancer and ashestosis, of whom only one was a man working under conditions now prevailing in the industry. The additional 10 patients making up the total of 31 described in the Annual Report of the Chief Inspector oi Fac tories for the year 1947 had all been exposed prior to 1932 and I did not attempt to locate autopsy protocols describing them. It was the consensus of Dr. Gloyne. Dr. Wvers. and Dr. Merewether that the nature of the disease, ashestosis, as seen in England has changed so that it is less & common and less severe in individuals whose employment in the industry has taken asbestos, place onlv since 1932. It was the consensus that a lung tumor hazard formerly c degrees existed in this industrv in Great Britain but that there is no evidence to show that .11 among such a hazard continues to exist under the working conditions now prevailing. c patient It should he further noted that in the 1947 factory report Dr. Merewether shows d in two that a mean exposure of 16.5 years, with a range oi 1.5 to 40 years, existed in the e ; in the cases of asbestos workers who succumbed to lung cancer. Individuals beginning to mod- their employment in the 1930's are therefore only now reaching the mean age at which tumors might be expected to appear. The size of this group is not known, bcated by but the fact that it has thus far provided only a single case of coexistent lung cancer ,> that in and ashestosis argues that any lung tumor hazard has been greatly diminished, at tosis was least in point of time. Whether there will be any significant number of cases with lie cancer delayed appearance remains to he seen. -iV'll' <'ina in 1. Prof. King described his experimental studies on the use of alumina in pneumo ; England conioses. In the case of experimental ashestosis. alumina had no benehcial eflect21 Rhodesia 21. Wyers, H. : Ashestosis, Postgrad. M. J. 26:631-637, 1950. - " ;t 2.''-) IS M ' S T R I A L H Y C l l i X A AX1> OCX I' l ' A T O X A 1. MJ A> I C ! X! i in either oi two senes ol tests. 1 examined histologic;il sections of rat lungs that liad received intratracheal instillations of asbestos fibers. Studies of these lungs have been published- 1>rof. Kin slated that he had found no difference in the response of rat lungs to Canadian as contrasted with, Rhodesian fillers, nor had any epithelial changes been evident. .A few pulmonarv adenomas were present' in the slides shown me, but these tumors are known to occur spontaneouslv in rats and cannot be attributed to the instillation oi asbestos fibers. In regard to the animals chosen for experimental work, Dr. Glovne stated that he had found rabbits and guinea pigs more susceptible to asbestosis than rats He had not tested mice. (See Abstract of Discussion" at end of this paper for further comments on lung cancer in relation to asbestosis.) -iv, u i r ,, ,' i t f j y x In.the light ot the evidence that bladder tumors are caused bv beta-naphthylamme m the dye-manufacturing industry, production of this chemical was reportedly discontinued as of April. 1950, by Imperial Chemical Industries and by the Clayton Aniline Company, the largest British dye producers. They are said now to make suliomc acids by sulfonating beta-naphthol and animating jt later, thus avoiding the sta-"e tit which beta-naphthylamine is produced. This change in the manufac turing process should not only protect workers in the plants but also remove the potential hazard of distribution of free beta-naphthylamine as a contaminant of food dyes consumed bv the public. The question whether benzidine presents an occupational tumor hazard has loiw been debated. A recent paper by Barsotti and Yigliani presents an impressive series of cases oi bladder tumors attributed to benzidine exposure in an Italian dve-works. It is claimed that a majority of the patients had not been exposed to beta-naphihvlamine. A translation of this Italian study appears in an accompanying paper.-3 ' Dr. Kenneth Baker, of the Clayton Aniline Companv. .Manchester England described experiments showing that benzidine itself is not carcinogenic hut that men exposed to benzidine excrete in their urine a hvdmxvlated derivative, 3 3'-dihydroxy-4.4Mliammod,phenyl. a compound which lie demonstrated does evoke bladder tumors m miceA1 .Mice were given repeated subcutaneous injections of olive-oil suspensions ot benzidine or of its hydroxylated derivative 3.3'-dmvdroxv-4,4'diammodiphenvl. Xine mice were given the hydrnxvlated compound, and bladder papillomas developed m five and a bladder carcinoma in one. Xo bladder tumors were lound m the mice given benzidine or in control animals given injections of olive oil alone. Dr. Georg,anna Honser, Leeds University. England, kindly summarized for me the current work of her laboratory. The curious ability of beta-naphthvlamme to call forth bladder tumors in man and in dogs but not in other species has led t0 thc view that its carcinogenic action may depend on some metabolic change King. E. J Uegg. J.. ami Rae, \ .: Lflect of Asbestos, and <ji Asbestos and Aluminium, on tne Lungs ot Rabbits, Thorax 1:188-197, 1946. M . t z i n - 501' 1' o" and V '8,ian!- F~ : Blad(lcr L ^ -m s iron, Aromatic Amines. Med. lavoro - - 5 (lor English translation see A. M. A. Arch. Indust. Hyg.. this issue. ]>],. 234). 24. Baker. K. : The Carcinogenic Activity of Dihydroxy Benzidine, Acta Unio mternat contra cancrum 7(Pt. 1):40-51, 1950. ` SMl'I H--B R IT ISH A.XD E l ' R () ! 'E . l X T I M O R TR(>hLEMS ungs that sc lungs ce in the nor had resent in iy in rats Mated that ) rats. He impressed on it in men and dogs. In Dr. Houser's laboratory, the hvdroxvlated dernutne. l-amino-2-naphthol has been isolated from the urine of both men and dogs exposed to beta-naphthylamine. The conversion to l-amino-2-naphthol occurs less readily in the cat, even less so in the rat. The mouse is less able to convert than the rat, and the rabbit less able than the mouse. 1-amino-2-naphthol is toxic and unstable and is being tested for carcinogenicity by use of its acetvlated deriva tive. This derivative is being given to dogs and mice, species known to be capable of deacetylating it. They have failed to find 1-amino-O-naphthol in the urine of dogs, cats, rats, mice, or rabbits fed beta-naphthvlamine. aments on Bladder tumors, in the dye industry, are often referred to as "aniline cancers." There is no convincing evidence that aniline itself is carcinogenic. Prof. Dr. Druck- re_\, of breiburg, German}-, has recently reported experiments showing that aniline evoked no tumors when fed to rats.2-' Dr. Houser stated that she had obtained similar negative results with dogs fed aniline for live vears. -naphthvl- Oil orange E (commercial benzene-azo-/3-naphthol [Sudan I j ) has in recent . report edly e Clayton years been introduced to color margarine in England, but Kirby and Peacock of r to make the Ko}ul Cancer Hospital. Glasgow, Scotland, have shown that this dye causes i'.-' avoiding tumors m mice,-'1' and its use in human foodstuffs has been discontinued. manufac- At the hifth International Cancer Congress in Paris, the German delegation move the introduced a resolution, accepted by the Congress, requesting the Union Interna nt of food tionale Contre le Cancer to collaborate with governments and industries for unifica tion o! regulations on coloring matters for foods from the point of view of potential ; has long -ive series :re-works, naphthylijier.23 . England, hut that . 3.3'-dihy-e bladder : olive-oil h-oxy-4,4'<i bladder r tumors ections of cancer hazards.-'- 1 o exemplify the purpose of this resolution : The potent carcino gen paradimethylaminoazobenzeiie ("butter yellow") is not permitted in foods pre pat ed in some countries, but was said to be used in and exported from others. 1 discussed the question of synthetic food colors with, French. Belgian. German and English, representatives at the Congress. The Cancer Prevention Committee- now has on file copies of regulations governing the use of synthetic dyes for foods in these countries. Photostatic copies ot these documents can be supplied at cost on request. The following material in this section has been abstracted from them. Regulations applicable in the United States are contained in the United States Food and Drug Administrations Coal-Tar Color Regulations.-' A comparative list of dyes winch may be used in various countries has been published by the Society of Expert Chenusts of France.-1" ' I am indebted to Prof. Dr. H. Druckrey, of Freiburg, for advice on the German position.^ In West Germany the use of artificial food colors is governed by the law ot July p, 1887. This law was considered to be superannuated, and the German25*89 iri zed for ihylamine > has led he change 25. Druckrey H : Contributions to the Pharmacology of Carcinogenic Substances: Researches witn Aniline, Arch, exper. Path. u. Pharmakol. 210:137-158, 1950. 2- k/ rby' A:- a"ci Pt'a,cocky P - R- : Liver Tumours in Mice Injected with Commercial Food Dyes, Glasgow M. j. 30:304-3/2, 194). Muminium, led. lavoro 234). internat. 2/. Rc.-olution Xo. 11, Acta I'nio internat. contra cancrum 7: <Pt. 1) :24. 195u. 28. Coal-Tar Color Regulations U. S. Food and Drug Administration. 1940. (A com- of t lese regulations may be obtained from Superintendent of Documents 'Washington 5 d " C at a cost of 20c.) v... 29. Ruiz, I. S. L .: (,,) Rapport stir ks trauvaux dc la commission coiistimee par la 'k.ciete , experts-chimistes de France pour une revision de la legislation concernant la coloration des denrees alimemaire.-. Ann. falsifications et iraudes 41:520-528. 1948; (70) ibid. 42:47-51 1949 256 I X P l ' S T k ' I A L H Y G I k X l i A X 1) O C C GP A 'l O X A L M I U A U X L Research Council appointed a commission to recommend revision. Prof. Dr. Druck- rey is a member of this commission. Alter a search ol the literature, this commis sion issued a report3,1 listing 14 dyes which it considered adequately tested for toxicity and safe for use in foods. These dyes, together with their reference numbers in the Colour Index,031 are: . Acid yellow (Xo. 16). Sodium salt ol aminoazobenzene disuitonic acid with not more than 3% of the sodium salt oi aminoazobenzenc monosuh'onic acid. Tartrazme (Xo. 640). Sodium salt of 4-/>-suliobenzenc-azo-l-/>-suliophenyl-5-liydroxypyrazol-3-carboxy!ic acid. Quinoline yellow (Xo. 801). Sodium salt of quitiophthalone di.-ulionic acid. Chrysom SGX (not listed m Colour Index). Disodium salt oi l-aminu-benzol-2,4-disultonic acid-azo-resorcin. Carmoisine A (Xo. 179). Sodium salt of 4-sulio-a-naphtl alene-azo-a-naphthol-4-sulionic acid. Fast Red E (Xo. 182). Sodium salt oi d-sulio-a-naphthalcne-azo-ii-naphthol-O-sulionic acid. Amaranth (Xo. 184). Sodium salt of 4-sulfo-a-naphthalenc-azo-b-naphthoi-3: 6-disulionic acid. Cochineal Red A (Xo. 185). Sodium salt of 4-sulio-a-naphthaIene-azo-/3-naphthol-6: 8disulfonic acid. Ponceau 6R (Xo. 186). Sodium salt of 4-sulio-a-naphthalene-azo-f3-naphtlu>!-3: 6: 8-trisulfonic acid. Erythrosin, bluish (Xo. 773). Sodium or potassium salt of tetraiodofiuorescein (for coloring of whole fruits only). "Palatin--scharlach neu." Alizanthrene Blue R (Xo. 1106k X-dihydro-1 : 2 : 1' : 2'-anthraquinonc-azine. Indigo carmine (X'o. 1180). Sodium salt of indigotin-5: 5'-disu!fonic acid. "Briliiantschwarz neu." For the French regulations, I am indebted to Prof. Ren Truhaut, University of Paris. Prof. Truhaut is serving cm a commission of the French Academy of Medicine, which is charged with formulation of new regulations on food colors. In France, a late is the act of a legislative bodv (now the National Assembly). An arrte or dcret is an executive order promulgated by a ministry or other admin istrative office. Regulations setting forth coloring matters that may be used in specified foods and drinks were given in the arret of June 28. 1912. issued jointly by the ministries of agriculture, interior, commerce and industry in connection with the law of -Aug. 1, 1905, for the repression of frauds and falsifications in foods. The arret just cited was concerned as much with falsification of food? as with possible toxic action of coloring matter.-,. Therefore, the colors that could be used in certain types of foods were rigidly limited. Xo added color was permitted for margarine. In 1940, the Society of Expert Chemists of France created, a commission to study revision of the arrt of June 2S, 1912. The report of this commission recommended that auramine, malachite green, and methyl violet lie dropped from the list of permissible colors, citing certain references indicating a toxic action on the part of these dyes. .Approval of certain other dyes was recommended. The report of this commission contains a valuable list showing the differences between regulations governing the use of artificial food colors in various countries. A 30. Resolution, Deutscher Forschungsrat, Fachkomission zur Bcarbeitung des I.ebensmitteliarbstoffproblems Stuttgart, 1950. (7 pp.) 31. Rowe, F. M. : Colour Index, ed. 1, London, Society oi Dyers and Colourists, 1924. second repw. commission's Aug. 11. 1--' garnie. 1 he heahh by re:, azoxy-dyes a In 1949. ' published: >e\ sion ma: le a reviewed: con and in r ranc colors r.c; pc: into FraitCc against the rindig': iiUU. cause ca:::cer the artiticial the use c: in Tins act me:, food cob >r.> i- revoked at < siderat: >n b state.- ton; t used in n . part by a denotli'ir.g to ;. may be ca: carried: >on r table <h e- v. A -uni;;, and ha- rev Redme. <b to U- thrum for the use < hut that m ; document . ro .,, m n i (. U . l . ------ = eatiuu uruvi From ti. tries range : nut. n-.d 132: 33. Harri- 7 : 35-5 '. P 47 J i . :\ 0vi1! L mentation ci . i: S M I T H -- T R I T I S I ! .-IXD ! :.V K O R E A A T U M O R R R O K L E M S 257 I)r. Druck- second report of this commission 1"'1, revised the form of the list proposed in the lns commistested lor r reference commission s earlier report. Recognition was made of a government decree of Aug. 11. 1947 permitting the use of . A l o w All and yellow OH for coloring mar garine. 1 he commission stated that these two dves were suspect as hazardous to health by reason of the aromatic amine group in their molecules and recommended .it more than azoxy-dyes as preferable to amino-dyes shell as yellow AH or OH. In 1949, the Commission on Food and Nutrition of the Academv of Medicine gl-5-hydroxy- published several notes relative to the use of artificial food colors.3- This commis sion made a decision against using yellow AB or yellow OH in margarine. It -2,4-disulfonic reviewed complaints that some French food products were undersold both abroad and in hranee by products made in other countries and containing certain artificial .tiiol-4-sulfonic colors not permitted to French manufacturers but not excluded from being imported into France in foods of foreign manufacture. Nevertheless, the commission decided -sulfonic acid. against the request of French manufacturers for authorization of naphthol vellow S, 3 : 6-disul fonie indigo blue, and light green SF, yellowish. The latter dye has been claimed to naphthol-6: 8 cause cancer in rats.32334 Finally an arrte promulgated by the Council of State on Oct. 28. 1949, forbade -3 : 6 : 8-trisul- the artificial coloring of margarine, noting however, that there was no objection to the use ot naturally colored fats, such as palm oil. in the manufacture of margarine. ( for coloring This act means that the legislation now in force in France on the subject of artificial food color.-, is the arrte ot June 28. 1412. all subsequent modifications having been revoked at one time or another. Revision of these regulations is now under con sideration by a commission of the French Academv of Medicine. Prof. Truhaut states that this commission has given a decision against anv svnthetic dves being used in foods destined for human consumption. This decision was motivated in University part by a desire to prevent frauds, in part by the view that synthetic dyes contribute Academy of nothing to nutritive values but introduce into foods a class of compounds which food colors. may be carcinogenic in themselves or may contain carcinogenic contaminants Assembly). carried over trom materials used m their manuiacture. Naturally occurring vege *alter admin- table dyes were recommended to replace synthetic dves. be used in A similar resolution was adopted in Belgium at a cancer congress in 1939 31 -sued jointly and has recently been resubmitted to the Belgian Ministre of Health by Dr. R. election with Reding, of Louvain, Belgium. Belgian food-dye regulations have been supplied 'its in foods, to us through the courtes}- of Prof. Maisin by Mlle. M.-Th. Caihe. of the Queen "ids as with Elizabeth Anti-Cancer League in Brussels. Mile. Cailie advised that the legal basis i>uld be used for the use of food dyes in Belgium is contained in the arrt rovai of Dec. 10. 1840. >ermitted for [ but that in practice the use of 23 synthetic dyes is permitted. These are listed in a document obtainable from the Service d'inspection des denres alimentaires de nnmission to ; l'tat. 22 Place de Brouckre. Brussels. The Belgian list can be found in a publi `immission ->e : cation previously cited.33" 'ropped from From the preceding text it will be seen that the viewpoints in the several coun xic action on tries range from condemnation of all synthetic food dyes to approval of dves found mended. The nces between countries. A 32. Tanon, L. : Rapport de la Commission de l'alimentation et de la nutrition. Bull. Acad, nat. md. 133:337. 376 and 576, 1949. 33. Harris, P. N. : Production of Sarcoma in Rats with Light Green SF, Cancer Res. - Lebensmittel- 7:35-36, 1947. 34. Reding, R. : Des dangers de cancrisation rsultant de l'emploi de colorants dans l'ali us, 1924. mentation et en thrapeutique, Acta Unio internat, contra cancrum 4:735-754, 1939. -ii 258 /A h i S' ! ' RIAL H Y G I F X F AXI> OCi f P A T I (>X AI M F P I O X F lurmle m properly conducted tests on animals. Although cancer has been provoked by certain dyes in annuals, it could be argued that thus should not prohibit thetr hemg used m human foods, since there ts no evidence that man would r e W to them in the same manner as animals. Conversely, it could he itr-cd that a nega tive result ot an annual test does not prove the harmlessness of a dve for ,,.n L deriving these questions as to the value of animal tests m supporting decisions o permit or to prohibit any spec.fic dye is the fact that many dves are prepared rom beta-naphthylamme, which is known to cause cancer in man. It is not known whether tree beta-naphthylamme can be liberated m the human body from dves containing it m combined form, but free beta-napluhvlamiiie was stated to'be carried over mto the finished dyes to varying degrees m the process of manufacture Another highly carcinogenic chemical used in the manufacture is orthoammoazotoluene. . V. SOURCES OF S T A T IS T IC A L DATA OX OC'CITATIO .XAL FACTORS IN CANCER Great Britain - D e a th certificates for England and Wales are filed at the office o. the Registrar-Genera) m London. The most recent analysts was published in J4J and contains breakdowns of cancer mortality by age. site. sex. and geographic area.- It thus provides base-line data on the general population, which can he used as a _\ardstick to judge claims that cancer of any particular sue mav he unusually common m some particular group of workers. The death certificates contain state ments as to occupation. An extensive analysis of death-certificate data up to IWi lor cancer m relation to occupation has been made by the Chief .Medical Statistician r. Percy Stocks.-*" The most informative and detailed yearly account of industrial diseases m England ,s the "Annual Report of the Chief Inspector of Factories".37 193/>% urCi Pmrneiu to our field were published bv the Scottish Rational ideaith Insurance organization, as reviewed by Padlev.- This source has now been incorporated mto the new .Ministry of National Insurance. This ministry will issue annual reports through His Majesty's Stationery Office. The first ret/ort is soo-> to aPpear and will cover data of the past two years. These reports should furnish the most extensive data on morbidity, while the Registrar-Generals Review wT continue to atiord the most complete data on mortality. The reports of the Mimstp o< National Insurance will provide information on occupation in relation to disease mt it is doubtiul whether the system adopted for coding occupations will efistin- f U1S1 heUVeCn 0fhce an<1 !)lam Personnel. The necessity for making this d.stiiwkw haS ,,,,,,,,,,,,<1 Mr. E . \ Le>>, x ,, . Yor, ;v]kj 01,, ' tha; a h.yh m o O u f u.ikxt m lia m -o ^ ralm - pirsoni.d .<! a hazar<l,,u, mauA,: can Je diluted beyond statistical recognition when data are collected so as to include 1W5 . J ,CTM E`f r MOTMlf T " " W n- ' 0l' . , ,MuiK"!- Lf,uon- H,s IN '" " Majesty's SEta"tito"nery " -1 Office. 1949 publication is priced at 6 shillings. 6 pence.) ` ' h Sis V, , r. (This isg . U l u s o8b-pagi. 36. Stocks, Percy: Occupational Mortality. j,, The Pe<bstnr-G,-ne~,r r w . - 1 c , ment, London. His Majesty's Stationery Office. 1958. P t. H a , 4uu pp ~ ^ L"nia; " up`',t'_ 37. Amu,a! Report of the Chief Inspector of Factories for the Year 1948 1 onden Hi- Majesty s Stationery Office. 1949. (This 158-,,age report is priced at 5 .hillin'.'. , M e ? 1 r2ai 3 - S 7 R1947StUdit:S * * " d " ' tota8C in Ind" striaI * * * * . British 1. Social SM IT H --B R IT IS H A S P T.'TKOPhAX 'IT M u R PRO PI.PM S the same industrv's office workers exposed to no hazards other than typewriters and tiling cabinets.31. Occupational data based on more specific details of the actual job may be forth coming from a scheme described to me by Dr. J . A. II. \ \ aterbouse. oi the L niversitv of Birmingham (England), where data from hospitals in the Midlands are to be coded. The proposed forms contain items for cancer and also the following : Industry (C od eF ) Occupation Previous occupation Specify................................................................................................... years Specify................................................................................................... years and industry if retired............................................................... years Code F refers to a letter code which breaks down British industries into about a hundred categories. It is the code developed and used by the Ministry of National Insurance. The additional item for "Occupation" represents an effort to obtain more specific data on the individual's actual job within the industry. Recently, physicians have beeen required to file a card with the General Register Office for each cancer patient. These cancer records are in process of being analyzed bv Dr. Percv Stocks. From the design of the cards it is apparent that their chic: purpose is to provide data on matters of diagnosis, treatment, and fate. There is. however, one line designated "Occupation.................. " and the instructions request notation of any change in occupation in the preceding 10 years. This request lias evident merit and would have more if a place to enter the answer were provided. For example, a form used in New York presents the question as follows: Present occupation........................................................ duties............................... years employed.............. Chief previous occupation.......................................... duties............................... years employed............... Extensive information on skin cancer exists m Britain as a result of the \\ orkmen's Compensation Act. which recognizes the occupational nature of skin cancers due to pitch, tar. soot, bitumen, mineral oil, or paraffin and requires that these he reported. Evolution of this legislation and analyses of consequent medical findings have been reviewed bv Dr. S. A. Henry in the valuable issue oi the British Means Bulletin devoted to chemical carcinogenesis and elsewhere The largest single group of skin tumors reported from this source derives from the cotton textile industry, as detailed in my section on shale oil. In recent years, the majority oi cases have come from gas- and tar-works employees. The petroleum industry has contributed a negligible number of cases. It is interesting to note the great variety of trades in which skin tumors have been certified as of occupational origin, owing to exposure to one or more of the agents specified in the Compensation Law. Tints. 16 cases of skin cancer, in 2 of which, it affected the scrotum, have been reported, among optical-lens workers. The hazard for these workers has been traced to the pitch used to mount the glass for grinding. 1 could discover very little information on the populations at risk in the various categories of employment to which occupational skin tumors were assigned. In occupations from which only a few cases have been reported, it is thus not possible to evaluate the significance of the alleged occupational factor on statistical ground.-. Skin cancer is increasingly frequent with age. and some spontaneous skin tumor.-, are undoubtedly included in the groups attributed to occupational factors under the39 39. ! rw, E. A. : U-e of Life Insurance Record- for Cancel' Studie.-, A. M. A. Arch. Indus* Hyg., this issue, p. 198. 2<>0 IXIH'S'I KLM. h .YF A S M (KX L K X T J U X . 1L I L P L X L British law. In the- absence of statistical criteria for certain occupation- involving small groups, decisions as to the occupational nature of a tumor can sometimes be reached on other ground.-, bur example, I 'roi. ]. R. Squire described to me a patient who used his bare hands in molding battery casing- from hot pitch. This man s hands bore several cancers, the occupational origin of which could hardly be questioned. Similarly, an occupational causation is indicated in cancer oi the scrotum, which is an uncommon site for cancer in persons not exposed to recog nized carcinogenic materials. A statistical study of cancer of the lung and of the larynx has beer, published by Sir Ernest and Lady Kennaway,4" who have also reviewed publications of the General Register Office pertaining to cancer.401 As brought out in mv section on asbestos, valuable data on lung cancer have emerged through the Pneumoconiosis Board. A statistical study of bladder tumors with reference to occupation is being conducted by Dr. R. A. M. Case and his associates at the Chester Beattv Research Institute, London. This group is inquiring into the occupational histories of bladder-tumor patients seen at various hospitals in England. Industries in the selected areas are collaborating to provide data on the populations at risk in situa tions where bladder tumors appear to have some connection with emplovment. I-rancc.-- I he October, 1949, issue of the Semaine des hpitaux de Maris was devoted to occupational medicine. The leading article, bv Prof. Ren Labre, dean of the Institute of Industrial Hygiene, University of Paris, described the develop ment o! industrial medicine and pertinent legislation in France.4- According to recent French legislation cited by Dean Fabre, a report on diseases of occupational origin must be appended by the factory physician to the annual financial report to the company. Prof. Ren Truhaut, of the University of Paris, advised that a decree of lune 23. 1947, requires official notification of occupational diseases caused, am.mg other things, by "pitch, tar, bitumen, asphalt, mineral oils, paraffins, and other sub stances irritant or carcinogenic for the skin." The French law in this respect is similar to the section of the British Compensation Act cited above. The notifica tions must be made to the Ministre du Travail. K'o substantial amount of information is yet available from this source. The same is true of cancer statis tics being compiled under the direction of Dr. Pierre Denoix at the Ministre de Sant Publique. The French Anti-Cancer League does not have data suitable for study of occupational factors, according to the statement of it- director. Dr. Huguenin. Dr. Huguenin and his associates have, however, published a studv of the occupational history of 112 individuals with lung cancer. Tbev noted that 18 were metal worker- and suggested that mists of cutting oil- laden with, metal lic dusts may have piaved a role.43 40. Kennawav. E. 1... and Kennaway. X . M. : A Further Study of the Incidence of Cancer of the Lung and Larynx, Brit. J. Cancer 1:260-298, 1947. 41. Kennaway. E. L. : The Data Relating to Cancer in the Publications of the General Register Office, Brit. J. Cancer 4:158-172, 1950. 42. Fabre, R. : L'hygine et la toxicologie industrielles dans leur rapports avec la mdecine du travail, Semaine hop. Paris 25:3065-3073, 1949. 43. Huguenin, R.; Fauvct, J., and Mazabrand, M.: Rle ventuel des nbulisations d'huiles industrielles dans la pathogenic des cancers bronco-pulmonaires, Arch. mal. proie-. 2-48-51 1950. ' ' involving sometimes vd to me a pitch. This mild hardly mcer of tlie <i to recog en published itions of the . section on umoconiosis on is being ;y Research histories of tries in the ;sk in situa- ivment. Paris was i'abre, dean the developccording to ccupational :al report to ree of June mong other other sub ' respect is he notiheaamount of oncer statis*iinistere de ata suitable irector. Dr. bed a study . noted that with metal- nce of Cancer . the General . la mdecine j lions d'huiles 5 less, 2:48-51, - S M IT H --B RI TI S H A M ) T I R O T E A S TEMOR Pk OHL EMS An excellent book on chemical carcinogens has been brought out by Prof. Truhaut.44 Holland.--Dr. J. Yersluys presented a paper at the Fifth Internationa! Cancer Congress at Paris in which he stressed the need for distinguishing between occu pational and social factors in evaluating qn increased incidence of cancer in any particular group. P'or example, he found that farmers have a greater incidence of gastric cancer than males in general in Holland. However, gastric cancer was likewise more common in farmers' wives than in married women in general in Holland. Hence he concluded that the increased incidence of gastric cancer in this situation had a social rather than an occupational significance. This concept, earlier advanced by Stocks.45*merits consideration in the planning of occupational tumor surveys. Dr. Yersluys has published extensive statistical analyses of cancer deaths in Holland.40 Denmark.--Lung cancer appears to be more common in urban than in rural districts of- Denmark, while gastric cancer occurs with equal frequency in each type of area according to data published by Clemmesen and Husk.47 These authors considered that diagnostic facilities could account for the greater number of lung cancer cases in their urban population. Dr. Clemmesen stated that about 20'ye of the 4-million population of Denmark are now employed in industries. These are light industries for the most part, developed during the war, the country being traditionallv devoted to dairving and agriculture. He felt that intormation on the type of employment was not sufficiently accurate for statistical purposes. Other Sources.--I learned nothing of occupational tumor data that may be available in Xorwav and Sweden, where public health statistics are notably good. The dislocations of war make doubtful the obtaining of much data from Germany within the near future. A valuable Italian study on occupational bladder tumors has been referred to in mv section on dvestufis. Dr. Aage Grut, ot the Interna tional Labor Office in Geneva. Switzerland, indicated that data on occupational cancer hazards mav again be collated by that organization, which published a detailed work on this subject some years ago.4S At the Fifth International Cancer Congress, in Paris. I presented a paper describing experimental studies at Xew 'i ork T niversitv on carcinogenic petroleum derivatives 4:1 and a paper describing the general organization of occupational tumor investigations at the Institute ot Industrial Medicine. Xew b ork University."0 In 44. Truhaut, R . : be? facteurs chimic|ues de cancerisation. Biol. med. 38:1-47 and 8(M15, 1949. (This work is available in a 77-page reprint. 21 Rue Jean-Goujon, Paris. 1 45. Stocks, P.: The Effects of Occupation and of Its Accompanying Environment on Mor tality. J. Roy. Statist. Soc. 101 ( I V) :(E9-70b, 1938. 46. Yersluys, J. : Cancer and Occupation in the Netherlands. Brit. J. Cancer 3:lbl-1Sr, 1949. 47. Clemmesen, I., and Busk, d .: Cancer Mortality Among Males anc Pemales in Denmark, England and Switzerland, Cancer Res. 9:411-414 and 41 o--421, 1949. 48. Encyclopoedia of Hygiene, Pathology and Social \ \ chare Studied from the Point of \ tew of Labor, Industry and Trades, brochure edition, International Labour Ofhee. Geneva, 192s-19o4. 49. Smith, W. E.: Sunderland. D. A., and Sugiura K . : Experimental Analysis of the Carcinogenic Activity of Certain Petroleum Products, Acta C nio internal, contra canoruni 7(Pt. 1): 173, 1950. (See also footnote 6). 50. Smith, \V. E . : Environmental Cancer Program at the Institute ot Industrial Medicine, New York Universitv-Bellevue Medical Center, Acta L'nio intermit, contra cancrum, to be published. n I' [IE4's- f X w . Jf ;f m it it 262 IXDL'STKI.-IL H i u l E X H .-/.YD OCCl'P.-lTHJXAL MF.D1CIXE July. lu50. a conference was held at Oxford dealing with cancer in relation to sociological and environmental factors other than occupation. Proceeding.- of this conference have been published.''" ABSTRACT OF .DISCUSSION' D r. P aul C artif.k, L'Annonciation, Quo.. Canada: I have been asked to describe our experi ence at the Thetford Industrial Clinic in Quebec, where we see men engaged in the asbestos mining industry in Canada. Table 3 presents data on eight cases of primary cancer of the luna which we have detected among 4,000 asbestos workers between 1940 and 1930. In addition to those listed in the table, there was a case in which there was Quite a definite clinica. and radiological history of cancer of the lung but for which, uniortunatclv, no autopsv was performed. Also there were three other cases with a strong suspicion in favor of a cancer of the lung but lor which no sufheient data are available. On analyzing these data it seems obvious that many points would need discussion before anyone will be able to establish a causal relationship between these pathological finding- and the asbestos factor. Is it not more logical to think that the same causal factor will produce the same type of tumor, and, therefore, why do we observe such a variety of malignant tumors : T able 3.-- Cases of Carcinoma of the Lunas Defected A mono 4,000 Asbestos U'orkcrs 1940-1900 Patient J. A. -rt. .-i. A. L. L. G. L. L. E. G. C. B. \v. e. Year- of Exposure 2-i *21 11 in 2 None -mn Meant None Year.-' in Industry 84 2.i 21 IT 20 14 7 Aue at I>euth ;,o r*7 :>i o4 (it, 04 o:> AG H-tu-us Minimal Minimai Advanced None Minimal None None Typ'M.iTiihiur BronchoLMHiic earainoma Uronelioeeiiie ea rciiioma Media-'t in a) lympho-areon.:; u it ii ptdim.na re met a-i a>;l v.:'oneiu>ee:jic ea rviiioma Pleura! mevttilii'lit.nHi'* Biomliuernic careinunm ! t ho ra at 11 uii; v Pieural Dje-i.1heiiolna * * *'*">ar.| Nom enc la ture o f Iiiscascs muf O pe ra ti ons" puMi.-!,r,i l,v the A.'.ini.-iiii M.-Pa al w - u o ' . ' n.n U%ew tor, I lie BlakistoD C om p an y , 1UK; sugg ests the term me.-otheliai -areumn." ' _ K,r a moment we may assume that the asbestos fibers might produce a bronchogenic car cinoma in asbestotic employees with significant exposure, then only two ca-es of the series w o u ld ser\ e a- etidence because the cases of mesothelioma or lymph,.-arcoma and ease- without exposure or without asbestosis do not have the condition.- required. As a last remark, it would appear necessary that any statistic- on occupational cancer of tinlung. to be conclusive, should indicate the precise variety of lung cancer. . Mk- Edvakii A. Lkw. New York: The difference in the frequency of lung cancer in personwith, asbestotic lung- as compared with the large group of silicotic- provided by the Pneumo coniosis Board seems impressive. However, one might wonder whether the two group- had been examined for cancer with equal care. I am impressed by the fact that wlien different group- of lungs were studied by the same observer. Dr. Gloyne. the differences in frequency of lung cancer were much less. It we restrict our attention solely to Dr. Gloyne'* series, I am not sure that the differences are statistically significant. D r. A. j. L axza, New 1 ork : I think 1; is important to distinguish between cases of clinically recognizable and fatal lung cancer, on one hand, and case- in which the diagnosis of lung cancer has been made as more or less of an incidental finding at autopsy, on the other. The English claim lor an association between lung cancer and asbe-to-is has been based, it seems to me. on data obtained from lungs that a pathologist has searched with a microscope. I wonder how many 51. Conference on Geographical Pathology and Demography of Caneeer. j. Xut. Lancer In<t. 11:627-662. 1950. ' \ . 'r '. . : .. caw- <: :d sa tr.e id. ljr.. cancer, it : work'T' r great earn ou;y one : lioiua. Tiii D r . 1 i '.i .- cinmrna. 1 ; to exchanu 1it rep', silka-'i- a: Pnvuntov- : a n.a> >na'! .senethe fa:n..r tile hfin'e.' T i< o f 1a d.c c; j >' s it: ID." :::: re 1e r ' e d > tam-.u- g idiiot..e ra ; ns ere .y a: W ' i relation to lings of this ibe our experi- n the asbestos- A cer of the lung quite a definite - eiy, no autopsy cor of a cancer 'V -cussion before 1 ai findings and e same type of sf'CStOS A .iv T .! rcioma treiooma ;*ho^arcoma :y inethta.i? .! rciDOina liuma* .t rciuoma rcinoma coma 1--iical Association mchogenic carthe series would ! cases without 3 al cancer of the ancer in persons riy the Pneumouruups had been Yerent groups of y of lung cancer not sure that the ases of clinically 1- of lung cancer r. The English seems to me, on onder how many Cat. Cancer Inst. s u m i- i- u < r n s u a \ i > h c ia h 'Ha x 'r.Mi'N Pi>HU:U> 2 ( i3 cases of lung cancer would be fount! it lungs from am rt *a' population were subjected to tin. yainc minute scrutiny r ^ Dk SMITH In regard to Dr. Cartier's query a- to the significance <> different tyi.es .I lung cancer, it mav he pertinent n, note that a diversity of tumors was found m the lunm m tm-tn.oc workers reviewed by Ur. Anna Bactjcr. Experimentally. the polyeydtc hydrocan,o,,s etokt a great variety of tumor types. If asbestos is carcinogenic. I would not expect m only one type of tumor. 1 am interested in your observation ot two cases ot )' L"r`` `'(' v lioma. This is a rather rare tumor. In examining pathological mateua sen. us tint.) - ` Dr Hinson, we found among six cancerous asbestouv lungs two presenting a \ eo at a < cinoma. These tumors are often diagnosed as "pleural mesothelioma." 1 should very much like to exchange slides with you. ... f In replv to Mr. Lew and Dr. Lanza, it was my understanding that the English ^ ses silicosis and their cases of asbestosis were handled in the same genera! tashiot, througn the Pneumoconiosis Board and that the lung cancer rate found m s,booties could the. co r e sere s a reasonably satisfactory control for the lung cancer ran- ... cases o. asbestosis In U series of 81 cases of lung cancer m the several pneumoconiosis groups and m the control greu, , the tumor was evident in the gross in all except (,. Some of h,s materia, was destrojec. dun ,, the bombing i London, but his recollection was that all ot the cancers m asbestotics t recognizable in the gross. Dk. JOHN L. P ool. New York: Have experimental studies thrown any light on the question of lung cancer in relation to asbestosis.' Dr S m i t h - In 1041. Xordmann and Sorge in U -nm ny claimed to have produced cancer in the lungs of mice by exposing then repeatedly to asbestos dust. Them statement dtatyaneer had resulted in 20D- of their exposed animals is occasionally quote;.. Actually. c. -- - referred onlv to two mice, one of which had a type of tumor that occurs common,y as a spon taneous growth ,11 mice. The other they considered to he a squamous cell carcuioma. bin t . photograph does not impress me as that c.t epidermoid carcinoma It seems ra.net to -D - merely an area of squamous cell metaplasia.