Document ExVR2QkZb0ZYOvVVpDDbyKwVR

FILE NAME: Texaco (TEX) DATE: 1945 May DOC#: TEX008 DOCUMENT DESCRIPTION: Minutes of the API Medical Advisory Committee Meeting For Information Only - lot for Pdblieatio. . AMERICAN PETROLEUM INSTIIOTI \ MEDICAL ADVISORY COMMITTEE Minutes of. Mooting St, Ionio, Missouri MEMBERS PRESENT: Molver Woody - Chairman D. V. Stroop Sseretaxy J, M, Adams V, 0, Armstrong V. C, Baird F. F. Boys D M. English T. M, Frank A. X. Hoag R. A, Jowott U. N, Nswquist X, X. Percy B* B, Reeve 0. S* Somerville MEMBERS ABSENT: Ym Russell Levis W. A. Morrison J. F. Feattle H, S. Thomson ASSOCIATES PRESENT : X. V, Adams L. C, Board, Jr* R, S, Bons ih R C, Colo Wm. Orant, Jr. H, R. Kemmerer A, J, Ko owing, Jr. E, P. Lankelm . #, U, futkins > Standard Oil Co, (Indiana), Socoqy-Vacuun Oil Co., Inc. Standard Oil Co. (N.J.) . Phillips Petroleum Co, Humble Oil & Refining Co* Shell Oil Company Socony-Vacuum Oil Co., (Lubrite Standard Oil Co, (OhioX: v 'T^e.femas Company Sinclair RefiSiig Co. Chicago, 111* , Now Tork, N. Y. , Vo York, N, I. Bartlesville, Okla. Houston, Texas . Wood River, 111. Div.) X&st St. Louis,111. Cleveland, Ohio New York, n J y . East Chicago. Ind. GUESTS:. . . Ya, V. Brooks, U.IC Phillips Petroleum Co. R, K. Gould F, F. Heyroth, K.D* Kettering Laboratory Phillips, Texas Bartlesville, Okla. University of Cincin nati Choice of Chairman for 19^5 Following a review of the origin and purpose of the Kedlcul Advisory Committee, Mclver T/oody was chosen to serve as chairman for 19^5 ' JAM 016809 Medical Prob lene in Hydrocarbons API 06766 By invitation Doctor Keyrctb reviewed data and sources of data on the toxi.v^v recently havr becoa- important because of the rapid Actions * The coasittee tendered Doctor Heyroth a vote of appreciation and thank for his presentation and requested him to send a copy of his review to the secretary so that copies could, he distributed to members and asso ciates III List of Current Medical Problems A canvass of members resulted in the listing of a number of substances and mixtures which may be injurious to persons through contact, absorption, or inhala tion . In addition a number of subjects involving matters of policy and administra tive practices were suggested for committee consideration. 2be committee discussed several base* for classifying problems for inclusion it its.program of work, as follows: . * 1. By groups of substances or mixtures, such as types of hydrocarbons, inhibitors, additives, catalysts, or acids. . 2. By the manner in which substances nay injure persons, such as skin _ contact, absorption, or inhalation. 3. By the method of solution to be used on problems, such as cooperative compilation of clinical data, literary research, or laboratory research. Action: The committee did not agree upon a comprehensive classification of the full list of problems but it was in agreement on four studies which should be initiated in 19^5 . as follows: 1. The study of medical policies and practices and fcrzralation of . tentative procedures for guidance of medical -men in industry. . . . 1 2. A study of chlorinated compounds, particularly chlorinated cutting . oils used in petroleum products, and of their effects. 3* A study of possible carcinogenic properties of hydrocarbons and . petroleum products. Preliminary reviews and studies as to the toxic effects and properties of hydrocarbons, products and substances other than those included in items 2 and 3* The chairman was authorised to appoint four subcommittees to undertake these studies. Notes by Secretary: (1) An outline of the field of interest of members, as developed at the meeting, is appended to these minutes. (2) The chairman announced the memberships of subcommittees, as follows: JAM 016810 API 06767 . -3- a. Subcommittee os Medical Policies and Practices E. A. Jewett, Chairman-- J, M. Adams T. U, Prank . W. A. Morrison -- J. P, Peattie- 1-** KI.. S8.. TPheorcmsyon -- M Mclver Woody, Ex Officio D. V. Stroop, * * b. Subcommittee on Chlorinated Compounds P, P, Boys, Chairman A. 2. Boas .... U. H. Hewquist B, B. Reeve Molver Woody, Ex Officio , D. T. Stroop " * * c. Subcommittee on Carcinogenicity U. B. Hewquist, Chairman J, M, Adana ' A, 2. Hoag Wru Russell Levis I, E. Percy Melver Woody, Ex Officio . D. V, Stroop, " d. Subcommittee on Permissible Concentrations V, C, Baird, Chairman W, 0* Armstrong ~ D. U. English T, M. Prank 0 S. Somerville Mclver Woody, Ex Officio D, 7, Stroop, " " IT Contribution and Dissemination of Information Contributions of literature reviews were contributed to the Committee by the iO'Miillg# : . " 1. Library of the Technical and Research Division, The Texas Company . "The Garcihogenicity of Bituminous Compounds,* April 30, 1 9 ^ 2. Chemical Division, Socoty-Vacuun Oil Co., Inc, "Carcinogenic Hydro carbons," April 27, 19^5 JAM 016811 API 06768 API 04606 |MUCAN PHHUlEUM'NS.W* \ JAM 014839 API 04607 API HISTORY OF THE subcommittee ON CARCINOGENICITY 19U5-1950 JAM 014840 ' ) For Wormatlon Only - Wot for Publication of infonnation to Members of API Medical Advisory Committee. __________ _______ ___________________________ 6-13-45 ATTENTION . . Technical Memo No. 45-214 Chemical Division Socony-Vacuum Oil Co., Inc. Research and Development Laboratories Paulsboro, New Jersey April 27, 1945 Mr. P. V. Keyser, Jr. Dr. A. A. O'Kelly Dr. W. P. Hawthorne .... ' Carcinogenic Hydrocarbons, Literature Survey A brief literature survey of the cancer-producing hydrocarbons has been made as requested by Dr. L. C. Beard in his letter (if. M. Holaday/ P. V. Keyser, Jr.) of April 12, 1945. ' , Carcinogenic activity has been noted in various types of compounds including hydrocarbons, amino, &zo and nitro compounds, hormones, and in organic compounds. This report will be confined to the hydrocarbons and hydrocarbon fractions identified as carcinogenic. Most of the carcinogenic hydrocarbons were originally identified in the pyrolysis products of coal, wood, petroleum and shale. In some cases these hydrocarbons exist, as such, in the original materials. The active hydrocarbons are almost without exception polynuclear aromatic hydrocarbons and are conveniently classified under the parent hydrocarbons from which they might be derived. Thus, the three main types are classified as benzopyrenes, cholanthrenes, and benzanthracenes. Identified Carcinogenic Hydrocarbons (7).(22).(45), (24) i (12),(10),(5),(28) i (29),(38),(47) I. Benzopyrenes 1 ,2-benzopyrene 3,4-benzopyrene 1 ,2,3,4, dibenzopyrene II, Cholanthrenes cholanthrene 20-methyl cholanthrene ' 16,20-dimethyl cholanthrene 20-ethyl cholanthrene 15,16-benzdehydrocholanthrene JAM 014841 -end For Information Only - Wot for Publication ^ A contribution of information to Members of API Medical Advisory Committee. _______ ._______ 6-13-45. IHE iiBCINOQENICIT OF BITUMINOUS COMPOUNDS WHr Technical Resefttfth,Division New York JAM 014848 NOTE In view cf the immense amount of published information on various phcses cf the cancer problem it should be emphasized that this literature review gives only a rapid survey cf developments in the field of cancer research as applied directly to the petroleum, coal tar, oil shale and allied industries, While it is far from being complete, yet it is believed that most of the important work in this particular field has been covered, either in the report itself cr*in cne cf the bibliographical references given in the appendix and referred to at the bottom of page 1. U. P. Doss JAM 014849 THE CARCINOGENICITY OF BITUMINOUS COMPOUNDS It has long been recognised that the incidence of skin cancer is greater among workers in certain industries and occupations than among the population as a whole. Attention was first directed in 1787 to the very high death rate result ing from scrotal cancer cf chimney sweeps; it is eight times more common in these workers than in the general public in Ehgland, and in the United States the ratio cf cancer cases in chimney sweeps is double that of the general population^. In practically all cases it is the scrotum that is attacked; this is also the site in mule spinners cancer discussed later. Workers in other industries coming into direct contact with tars, pitches, shale oils, et?. likewise shew a high. incidence cf skin cancer, for example, laborers in plants making briquettes, tar reefing, wood preservatives, artificial gas, insulating compounds, shale products, etc. ` However, in spite cf the recognition of the fact that bituminous com pounds were apparently the cause of skin cancer, it was- not until relatively recently that skin cancer was produced in laboratory animals by direct application of tar. This was accomplished by the Japanese investigators Yamigawa and Ichikawal22 in 1915. Since then a great deal cf very careful work has been done in synthesizing and testing various organic compounds, particularly polycyclic qydrocarbons and derivatives. For lengthy reviews of this work, see References 8-12, 14, 17, 20, 22, 23, 26-29, 32-34, 74, and 87; particularly the review by J. L. Hartwell cf the National Cancer Institute covering 696 chemical substances, cf which 169 are reported to be carcinogenic^-# L. F. Fieser summarizes cur knowledge in this field as follows^: . "As judged by all available data for the production of skin and subcutaneous tumors in rats and mice, methylchclnnthrene probably is the most potent of the known chemical carcinogens, systematic studies cf synthetic model compounds have shown that the methyl group is of no intpertonea te the functioning of the compound; . . that much, if net all of the efficacy of cholanthrene is retained in the analogous hydrocarbon 5,10-dimethyl-1,2-benzanthracene; and that the most significent structural feature tf chclanthrene or methylcholanthrene is the 1,2-benzanthracene ring system with a JAM 014850 I carbon substituent at the meso position 10, 10-liethyl-l, 2-benzanthracene evokes sarcomas in mice nearly as rapidly as methylcholanthrene, and, though it is distinctly less effective in the production of skin cancer, the substance constitutes the nearest approach in a simple model compound to a simulation cf the biological properties of the hydrocarbon of more complicated structure, "Ail twelve possible monomethyl derivatives of the inactive 1, 2-benzanthracene have been synthesized and tested for carcino genic activity, and, of these the 10-isomer is the most potent. The meso-substituted 9-methyl compound stands next in order of potency, followed closely by the 5-methyl derivative, which produced sarcomas in mice with a lutent period about twice as long as that observed with 10-raethyl-l,2-benzanthracene. Methylcholanthrene and benzpyrene can be regarded as 1, 2-benzanthracenes substituted at the meso positions 10 and 9, respectively, and in model compounds the combination cf the two types of substitution is particularly favorable, 9,10-Dimethyl1,2-benzanthracene produced skin tumors in mice with remarkable rapidity and in this test surpasses methylcholanthrene in speed cf action, though it is less effective when administered.by subcutaneous injection. The thiophene isologue of the hydro carbon has comparable properties," Numerous attempts have been made to isolate the definite carcinogenic compounds in coal tar by means of distillation, solvent extraction, etc.73, but lfoile very potent fractions have been obtained, the individual compounds have been difficult to separate, Kennaway and Hieger ^ proved the carcinogenicity cf 1 ,2,5,6~dibenzanthracene, the first pure carcinogenic hydrocarbon known, m ' Cock, Hieger and Hewitt in 1933 isolated 1,2-benzpyrene, 4,5-benzpyrene and 1 ,2-benzanthracene and estimated that the original coal tar pitch contained not less than 0,003% of the potent 1 ,2-benzpyrene, Several investigators 22, 24, 25 have attempted to correlate carcino- genesis with fluorescence. For example, the cancer-producing material formed by the action of AlCl^ on tetrahydronaphthalene shows a blue-violet fluorescence, shewing three bands, 4000, 41SO and 4400 A.U., which are similar to the fluorescence spectrum of 1,2-benzanthracene A4, Kennaway and Hieger 62 suggest the possibility of the use cf the fluorescence spectrum for-the preliminary ination of materials suspected of being carcinogenic. JAM 014851 API 04619 -3 - An important fact brought out by several investigators is that the temperature to which a tar, shale oil or petroleum oil has been subjected determines its carcinogenic activity. In general, it would seem that temperatures up to 500C. are without effect 52 but above that temperature carcinogens are formed, the maximum yield lying between 800 and 900C. 53 59, Tar and pitch from gas works are far more active than that from coke ovens 58^ accounting fcr 10% cf all cases of tar Cancer in the United States while the coke oven product causes only 5% ^3. While petroleum residues resulting from moderate heat treatment are inactive -^0, yet by passing an inactive California petroleum through a cube at 880C. Kennaway and Leitch obtained a very active carcinogen 59, 60, ]fiven an inactive medicinal paraffin oil heated to 380C. under 50 atms. pressure acquired . some carcinogenic activity Kennaway 56 likewise obtained aux active material by passing isoprene through a tube filled with and heated to 820C. Watson *^5 achieved similar results with turpentine at 850C. Acetylene yields an active product on being passed through a red hot tube 59 but it must be pointed out that treatment with AlCl^ at room temperature also produces an active coapound ^1 . - On the other hand, synthetic lubricating oils produced by AlClj polymerization at temperatures up to 150C. were entirely inactive ^1. It is suggested that the condensation products of acetylene are of a more complicated nature and probably more unsaturated than those obtained from ethylene. The carcinogenic activity of tars depends apparently not only on the temperatures of their formation but also on the chemical compound used as the bas stock For example, a tar made from pinene at 850C. was far more active than one from turpentine made similarly, the relative potencies being 100:19. Pinene tars made at 500, 600, 750, 850 and 950^0. had relative potencies JAM 014852 m >t nas2-0 -iv . of 0, 12, 2L, 100 and 4. Oxidation of a synthetic tar at 100C. reduced its potency from 100 to 3, and at 150-160C. its potency fell to 0, Oxidation with an acetone solution of KlinC^ reduced the potency to 24; with pyridine au a solvent, almost to 0, The active constituents of synthetic tars fcrra crystalline picrites, the remaining filtrate being almost inactive, and the plcrato extremely * ' t . Shale cil is carcinogenic, probably as a result cf the hijh temperatures to which oil shale is subjected 10^, However, temperatures below 400CC. give a relatively inactive product, 500cC. and above being required In England where high-temperature tar is used in briquette manufacture, there are many cases cf skin cancer aneng tho workmen, which is not the case in France where the low temperature product is used* The greatest amount of investigation cf any type of occupational cancer. has been carried cut on mule spinners cancer in the cctton mills of Lancashire, England. Scuthara and Wilson 88 in 1922 first called attention the excessive occurrence of cancer in mule spinners. Women workers are not affected and about 70i of all cancer among mule spinners is cf the scrotum apparently due to the fact that a mule spinner at work walks to and fir in front of his machine, . leaning over the moving frame from time to time to join up broken ends of the yamr The base cf the frame is on a level with the groin and the spindles on the frame as they rapidly revolve throw off oil from their bearings onto the clothes. In the hot mills the men perspire freely and so wash off the natural grease cf the skin, thus allowing the oil closer contact 15, Irritation by the trousers Mid overalls also helps the process. It is interesting to note that no trouble of this sert was noticed in England until mineral oil replaced animal and vegetable oils as a lubricant 16, Henry estimates that 0,25% of all cotton mule spinners in England suffer from scrotal cancer. On the other hand in the United States during 1926, for example, there were only 33 deaths from cancer of the JAM 014853 -5- scrctura, of which only three cf the victims were textile workers and three were mule spinners; four cf the six were born in England and the ether two in Canada ^5, which tends to show that mule spinner cancer is rarely contracted in the United States. In a woolen mill in the United States employing about 200 mule sninntsrs nc- cases of scrctal cancer were found Since the method cf operating this equipment is the same in both countries this striking contrast is attributed by Hamilton ^ to the fact that Scottish shale oil is used in the Lancashire mills. However, the literature is not entirely clear as to the origin and type cf the oil used in Lancashire in mule spinning 53, Leitch ^ brings out a fact of possible significance, to the effect that cancer is net known in woolen spinning mills, even though the same machines are usd as in the ccttcn factories, but points out that the room temperatures in the cotton mills are much higher, possibly resulting in mere relaxation cf the tissues cf the scrotum and permitting entry of oil into the sebaceous follicles. Bred:bank ^ however, states that in the woolen industry piecing cf broken ends cf yam is dene with both hands with a forward level bonding movement rf the body and thus there is net the same friction of the clothes cn the scrotum as in the cotton mills. He admits, however, that the same cil is used in both types cf mills. , . As a result of the preliminary investigation of Scutham and Wilson mentioned above, the Manchester Cancer Cc-nmission, consisting of more than fifty members, was organized in 1925 under the direction cf Dr. C. C. Twort to investigate the mineral oils used in Manchester cotton mills. Lubricating oils from the various fields throughout the world were found to have widely varying degrees cf activity. A semple of Venezuela oil was very potent while Russian and Pennsylvanian samples were cn an average less than cnc--tenth as active. Purified medicinal cil had nc carcinogenic pr-parties and several saponifiable oils, such as spem, olive, rape, cottonseed ani neatsfpet cil, failed tc produce JAM 014854 -6- tumors when applied to mice, even under the most severe experimental conditions. In general terns., the more saturated were the constituent hydrocarbons of the lubricating oil, the less capable were they of inducing cancer in experimental animals, the physical characteristics being the same ^lf This preliminary report was criticised severely in an editorial in the '`Petroleum Times of London in that while various oil companies (Anglo-American, Anglo-Persian and Shell-Mex) had contributed il.,000 for two years for the support of this investigation, yet the Manchester Cancer Commission had not availed itself of the services and advice of experts from the oil industry relative to the characteristics and methods of treatment of petroleum oils. The Institute of Petroleum Technologists, while making no definite criticisms at this time of the work of the commission, formed a committee of its own to follow closely the work in progress ^3, In 1934 Dr. A. E. Dunstan, Dr. F. H. Garner and Mr. James Kewley of the Institute of Petroleum Technologists are shown as members of the Manchester Commission '. In 1933, Twort and Lyth ^ of the Manchester Cancer Comaittee reported that by means of solvents, extracts were obtained of high refractivity and correspondingly high carcinogenicity Their recomnendations for the selection of an oil of low carcinogenicity were as follows . When selecting from several mineral oils with similar gravity, specify that with the lowest refractive index? when selecting from those with similar refractive index, specify that with the highest gravity; when selecting from those with similar refractivity, specify that with the highest viscosity; and when selecting from origin alone, choose in the following order* Russian, Pennsylvanian, Texas, Mid-continent, Mexican, Californian, Persian, . Rumania, Borneo, Venezuelan,shale. However, it should be emphasised at this point that these authors state definitely that "adequate refining of any of the oils handled, of no matter what origin, results in a product ....... . possessing only a very low JAM 014855 7' carcinogenicity" Also, that a single extraction of an unrefined distillate with SOg may profoundly lower the activity of a previously very dangerous oil, wniJo a second extraction may render it almost inert. They state that "it is probably commercially feasible to treat oils pf any origin, or oils of any degree of carcinogenic activity, so that they may be loss dangerous than even the very best of the straight oils used today". They evidently assume that untreated textile oils are used in the Lancashire mills. Lyth of the Commission further stated ^ that when the refract!vity^ of an oil was less than 0.5500 it was found to be non-toxic, while when the value was greater than 0.5600, the oil was highly toxic. Pennsylvanian oils and certain mildly treated oils were an exception. The iodine value of an oil sterns to afford an indication of its toxicity, providing the oil has not been treated and again the higher the value, the acre potent the oil. The toxicity increases in the same order as iodine value, except for Pennsylvanian oils which again . occupy too high a position. The permanganate values are hot regarded as of any value in connection with estimating the toxicity of oils. Lyth adds that extraction with alcohols, acetone, etc., clay and acid treatment, leads to a reduction in the potency, especially in the case of the more potent oils but a corresponding reduction in the refractivity does not always occur. Where a marked reduction in the refractivity does occur, there is, without exception, a marked decrease in carcinogenic!tyj with a marked increase in refractivity, a corresponding increase in potency. IShere the refractivity is not much altered, the potency may or may not be affected and further tests are necessary. . In spite of the apparent definite findings and recomaendations of the Manchester Cancer Commission, the Cancer Research Ccranittee of the Institute of fctroifcum Technologists 51 was not convinced that "the so-called incidence of JAM 014856 -8- cancer is in any shape or form connected with the use of spindle oils". No elaboration of this statement was given, but was possibly based on refined oils c-nly being used as textile lubricants. , An editorial in the "Petroleum Times" of London in 1937 once again attached the conclusions of the Manchester Committee, pointing out that only one oil from each of a number of countries was examined . In 1937 the Federation of Master Cotton Spinners Association sent out a letter to its members.reconmending that when purchasing spindle oils a guarantee should be obtained that the oil conforms to the specifications of the Manchester Cancer Commission, and that tests had shown that many of the oils in use at that time ccnfonned to the specification. While throughout the reported work of the Manchester Cancer Commission it is stated repeatedly that acid or solvent treatment of a potent oil greatly ' reduces or eliminates its activity 97, 102, 104, 71f yet in 1939 Twort and Lyth ^ investigated acid and clay treated distillates from a Borneo oil and found them to be active, the maximum potency being at a viscosity of 200-250 cp at 25cC. Molecular distillation gave a greater concentration of the carcinogenic material than was obtained by ordinary distillation at from 3-10 mm. In confirmation of previous findings the middle fractions of this Borneo oil were mostly responsible for pathological changes in the organs, A carcinogenic shale oil was separated by molecular distillation into fractions which were subjected to chromatographic adsorption. Two apparently pure hydrocarbons have been isolated and are being investigated 2*-09, A recent report (1941) by C. C. Twort of the Manchester Cancer Comniaaion 1^7 states that animal teats are variable, lengthy and costly and thata more reliable estimate of the carcinogenicity of oils can be obtained from the refractive index and viscosity. (Yet the data on which selection of these two properties was based were obtained by means of this variable skin test.) JAM 014857 > O T r\AC.-)C^ -9 - Vtoodhouse of the Birmingham Cancer Research Laboratory also states that mouse tests to determine carcinogenicity are difficult to correlate with human tendencies to cancer unless these animal tests are strongly positive or negative 221 For example, two oils were tested (a) from a spinning mill where no cases of mule spinners cancer had been recorded, and (b) from a mill wher six cancers had recently been reported. Mouse tests indicated slight carcinogenic properties in the caee of the two oils but a greater action on mice of (a) than (b). Dr. . M. Brockbank, chairman of the Manchester Cancer Commission, has briefly summarized the investigations of the Commission in a recent publication 2-6. He lists the hygienic precautions to be exercised in mule spinning and urges the adoption of the oil specification given previously by Twort. He also makes this interesting generalization: "As a general rule on oil that is strongly dennatitic yf]l not be strongly carcinogenic and vice versa". This is also mentioned by Kennaway ^ who states that cyclohexene (which is non-caroinogenic) is extremely irritating to the skin and should produce cancer if chronic irritation were an essential factor in carcinogenesis. ' . As mentioned previously, shale oils are very carcinogenic and in the Scottish shale industry the case incidence of skin cancer is about 0.1% per annum among the oil workers but 0*5% among the paraffin workers 53 (this is based on a 28 year record). This activity, of paraffin is restricted by Schwarz and Tulipan to the crude product, the refined wax being inactive, which view is supported by . Wood 219 who states that the active components are present only in the crude paraffin oils. Tilth regard to the refining of petroleum oils. Wood 220 made an investigation of refineries in Pennsylvania and found no scrotal cancer, which was confirmed by Heller However, Heller found evidence of carcinogenic compounds in Mid-Continent oils as refined in plants in Ohio and Indiana, Here oil boils are fairly common and in some cases lead to skin cancer. In one case JAM 014858 -10- a paraffin pressman in the Middle V/est was treated for "wax boils" for three years when a cancerous growth developed on the right forearm and was removed, but e-ight years later a second similar growth in the same place had to be removed Heller also found records of cases of skin cancer in another refinery, using crude from the Lima field; eight cases had occurred in this refinery and one was fatal. 11 of these cancers were preceded by warts. The length of exposure before malignancy appeared varied from four to thirty four years. The part most often affected was the scrotum and all but one man worked in the paraffin department. These cases were caused by unrefined oils and Hamilton M states that so far there is no proof of the occurrence of skin cancer in the U.S. from the use of refined lubricating and spindle oils which have been acid-treated. Heller & believes that the relative freedom from occupational cancer in the U.S is due to the mechanization of industrial processes, preventing direct contact with the pitch and tar; the extensive employment of negroes, who are apparently less subject to skin irritants than whites; the use of refined lubricants from crudes which are poor in carcinogenic properties, and the use of tar from coke-ovens instead of from gas works. Phillips 77 reports the particulars of a study carried out by the U.S. Public Health Service as to the incidence of occupational cancer in Texas. The records of.1190 individuals having microscopically verified skin cancers were analyzed, covering the period 1920 to 1940. The occupation of the largest group of these patients was outdoor work (farming and ranching); the work of housewives cooee next in order, followed by various activities requiring moderate outdoor life, The professions were next, followed by laborers end carpenters. The ' railroad and petroleum industries furnished few cutaneous cancers. Gafafer and Sitgreaves in a U.S. Public Health report issued in 1940 37 analyze 70 cases of cancer recorded for the male members of the sick benefit plan c* 40 oil refining company during the period 1933-38; there were 46 deaths. The death rate was 0.78 per 1000 and a frequency of 1.2 per 1000 (all U.S. death rate JAM 014859 -H- O.96 per 1000). Almost 70 of the deaths were related to the digestive system and the rate for this site was higher than in the total population. Deaths from cancer of the genito-urinary system was 6.5& of the total, compared to 15.0J6 in the case of the total population. . In 1934 Campbell-20> 21 na^e laboratory tests on mice with dust obtained ' 1 from tarred roads. This dust caused warts and cancer of the skin and in six months 24 out of 59 mice showed typical tar warts, half of which developed malignancy. This finding was confirmed by Kling, Samsonow and Heros, ^4, 65 also separated a substance containing the benzopyrene nucleus from the tar. However, Hogouneg ^ is doubtful of the danger from read tar since it usually takes years of direct contact cf coal tar to the skin to produce skin cancer* (Teutschlaender 91 calls attention to the fact that almost all industrial cancers require an exposure of about ten years before growth appears, although a few cases may arise much later.) Valade likewise is cf the.opinion that while primary lung tumors can be induced in mice painted with tar or exposed to inhalation of dust from tar roads, yet these results cannot be transferred to humans. Animals other than mice should be employed in experiments and an inquiry should be carried out on workers exposed daily to such dusts. While the manufacture of briquettes in England is attended by a high cancer rate, 58 since high-1emperature tar is used, yet in the few plants in the V.S. making briquettes cancer is entirely absent, partly due to the lack of contact with the hinder since the process here is entirely mechanized and partly due to the use of petroleum asphalt as a hinder, W. This finding was confirmed by Wood 3-20 in his investigation of briquette manufacture in Pennsylvania. The addition of glycerides 9 reduces the carcinogenic potency of mineral oils but not to as great an extent as lanolin. Speakman and Chamberlain ^9 state that while alcohols have not been used for this purpose there can be little doubt that such polar congjounds will reduce the risk of cancer formation by promoting emulsification, since an oil which is easily and completely removed from the skin JAM 014860 ho t 04628 -12- roust carry less risk than one which is difficult tc emulsify. These investigators also believe that polar compounds in a mixture with mineral oil may, however, function in yet another way. It is known that the carcinogenic agents of mineral cil when associated with unsaturated confounds are free to concentrate at any surface tc which the cil is applied, tho ncn-pclar paraffin molecules offering little or nc resistance. However, when oil-soluble polar compounds, such as' oleyl alcohol or wool-fat1 ether, are mixed with mineral oil they concentrate at the surface, excluding the less polar carcinogenic hydrocarbons. Sequeira stresses the necessity of absolute cleanliness of body and clcthing, the application of castor oil to exposed surfaces and medical inspection every three months. Brcckbank ^5 suggests a mixture of lanclin ani clive cil be applied to the skin. ' Duckham advocates the use of an oil-solvent cleanser similar tc the ether scap used in hospitals in order to remove all cf the lubricant from the pores 3. . In view cf the suggested use cf lanolin the following should be of particular interest: Dr, 5 . V. Cowdry, cf the Washington University School cf Medicine, St, Louis, has just announced (N.Y. Herald Tribune April 29, 1945) that cel-ls can be sensitized to become cancer cells by treating them with a substance which dees not cause cancer and which will even prevent powerful cancer-producing chemicals frem exhibiting that property. . . For example, when the powerful carcinogen methylcholanthrene is mixed with lanclin it is without action when applied to the skin of mice, although slcne it always results in cancer. However, when these mice were then treated with meihylchclanthrene in benzene they developed cancers more quickly and tumors of greater virility than mice which had not received the cancer-preventing treatment. _ MPD-VL . DH5 JAM 014861 +* * + f\ 13- RSJSHZNCSS 1 , Anon., Cancer from Spindle 011 Oil and Color Trades J., July 2, 1937* 38. A letter sent out "by the General Committee of the Federation of Master Cotton Spinners1 Association recommends that when purchasing spindle oil members should obtain a guarantee that the oil conforms to a specification of the Manchester Cancer Committee which recently Issued a foraila claimed to minimise the so-called cancer-producing elements of mineral oil-. Tests showed that many of the oils in use at present con ;form to this specification and are .obtained at regular prices. 2 Anon., Cancer and Mineral Oils, Oil and Color Trades J., 102. 695 (19^2) The report of the Manchester Committee on Cancer, issued for the . year ended October, I9U1 , states that in efforts to isolate and char- aeterize individual carcinogenic hydrocarbons from shale oil, recently appreciable quantities of crystalline material hare been obtained, but it is too early to discuss results in detail. As far as can be Judged, all fractions obtained from Venezuelan Oil by chromatograph! 0 adsorption are active. Proprietary colloids have varying effects, depending on the conditions of the experiment. A colloid containing a chlor-conprmnd was found loss efficacious than an olive oil-lanoline mixture as protection against the carcinogenic action of shale oil, while the reverse appeared to be thA case when the carcinogenic agent used was benzpyrene 3, Anon., The -Problem of Cancer Petroleum Times, 59 300 (193) (a) The following appeared in a recent issue of the British Medical Journal in connection with the use of mineral lubricating oile in the Lancashire cotton mills: "The Manchester Cancer t/oamittee, while studying the part played in the production of malignant growths by the lubricating oils used in cotton mills, has obtained information about the careinogenetic power of various oils and the concentration within them of a cancer-producing principle. In the course of this research, two pure compounds of known chemical composition have been proved capa ble of-producing tumors, and a study has been made of the factors which change a non-e&rolnogenio Into an active carcinogenic substance. Al ready some of the methods for destroying the caaoer-producing power of certain oils have proved to be effective, at least in part, and one method lad to the preparation of a purified oil which, when subjected to vigorous test, has failed altogether to produce cancerous growths; Representatives of the cotton industry, after oomparing this oil with . the .crude untreated oil have said that its lubricating power is unim paired, and the Manchester Committee ie therefore able to hold out the hope that before long it may be possible to put on the market cm oil a which fulfills the needs of industry without being a source of danger'to the workers" Assuming that the uae of spindle oils be such a source of danger, it almost necessarily follows that other lubricating oils which come into closer physical contact with the worker must be sources of higher potential danger than any of the light lubricating oils used in the .looms of the Lancashire cotton industry. It might be proved upon In vestigation that little difficulties would preseat thensslvss in the . production of a spindle oil which is non-earcinogenic, and lest the present attack widens itself to include the Whole range of mineral lubricating oile, it would be advisable to moke an investigation of the most embracing character, JAM 014862 API 04630 -33- examne., gas-work tar and pitch were responsible for 702$ of the eases while coke-oven tar and pitch were held responsible for only 5*k$, Coke oven tar is ouch the less injurious especially when cognisance is taken of the fact that coke-oven tar is used ouch more extensively. The presence of olefins in gas-works tar seems to be of particular importance and may be a cause of oil cancer. Occupational cancer does not occur in the briquet mfg, industry. Mineral oils vary in carcinogenic activity according to their olefin or unsatd. hydrocarbon content. There is no method for.the detn. of the amt. of olefins in the various crude oils; if such a method existed, it would be possible to measure the cancer- producing power of mineral oils. Cancer is not attributable to the occu- pagion of mule spinner in the U.S.. possibly because of the carefully refined lubricating oils used on the machines, thus ensuring relative freedom from olefins or unsatd. hydrocarbons. . . , Ut. Henry, S. 1. Study of Jatal Cases of Canoer of the Scrotum. J. la. Usd. J Assn., 102. 1667 (1937) bU. Bieger, I., Spectra of Cancer^-preducing Tars and Oils and of Related Sub stances. Biochan. J., 2U, 505" ! 1 {1930 . US. Hoffman, F. L. Mule Spinners Cancer. Monthly Labor Rev. of U.S., 7 >57- >75 (1928) . Ufi, Hoffman, W. J. Industrial Cancer. Prevent, Med., S, 7-3U (1936) Vne of the eeven types of industrial cancer discussed is cancer of skin in workers exposed to coal, tar, pitch, toot, shale, petroleum and arsente. They may cause an epitheliomatoue form of cancer* U7, Bogouneng, L. The Cancerlgenlo Hydrocarbons from Tar and the Tarring of Roads. Inn. Hyg* Fubl* Socials, 2J, 1-7 (1939) The cancerlgenlo hydrocarbons found in coal tar produce skin cancer in exposed worker usually only after direct contact with the akin for long periods of time* Xt is bslleved that man is much more resistant to the action of these materials than lab animal . . . U8. .Basti Bull. Ah ./: Owlng to indMtrt^ ie^elo^ent the'general population and factory workere in particular, are expoaed tn.m&xy new environmental factors, oany of which are dleeaee produclng. ,Qe^^^ional cenare are causad by agente areTtfcs Heavy metis, nitraas; aromaticamino onmpoundp.beni^.^besto.s .^niasral oil, soat, * radio-active sbttandee, ultraviolet radialion and X-rays. Th autHor cites statistics takea saialy fren the records of industrial eoncents, but points out thsir shorteomings Cancer of the urinary traet dote to coal-tar le the most recent addi tion to the list of occupational cancers. It is most frequent in the aniline lye and related industries*. *9 Home Office, Rept. of Departmental Gonm to Consider Evidence as to,Occurrence of Epitheliomatoue Ulopration Among Mule-Spinners. (London, 1926) Contains a bibliography on cancer among petroleum refiners- - II JAM 014871 a * /aft