Document QJV90GV1z7MdNGLpwz0qOx5ZL

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1953-1954 DOC#: API189 DOCUMENT DESCRIPTION: API History of the Subcommittee on Carcinogenicity HISTORY OF THE SUBCOMM1TTE ON CARCINOGENICITY i y53 i y 54 I i Copy from D. V. Stroop for Infornation of Members and Associais of the Medical Advisory Comaittee __ ______________________________ 1-19-53 ESSO LABORATORIES Standard Oli Development Company Medicai Research Division p. o. Box 51 Linden, N. J. 1 January 15, 1953 Mr. D. V. Stroop A m erican Petroleum Instituto 50 West 50^ Street Nev York 20, Hev York Dear Mr. Stroop: I am attaching a reprint of an article recently written by Dr. Hueper. I think that this article should be brought to the attention of all of the members and associates of the Medical Advisory Coonlttee of the API. Very truly yours, /s/ R. E. Eckardt R. E. ECKARDT, M. D. REE :11k Enel. - Environmental Cancers: A Reviev by Dr. V. C. Hueper Reprinted from CANCER RESEARCH Vol. 12., Ho. 10, pp. 691-97, October 1952. API 05554 V o A m e r ic a n P etr o le u m I n s t itu te 9 0 WEST DOTH STREET NEW VORK 2 0. N. Y. Tt j. Sullivan February 2, 1953 ,?T DiVIBiUU w* ------- - c/o Gulf Oil corporation Gulf Building Pittsburgh 30, Pennsylvania Dear Sir: As requested in your letter of Hovesber 19, the views of the Medical Advisory Committee meabership on the report and recommendations of the Working Group are transmitted for your consideration, as follows: 1. That portion of the report, as well as the first reeomendation, dealing with the epidemiological phase of the Kettering project constitutes encouraging support to recommendations . which have been considered and advocated repeatedly by the comalttee. The members need and welcome the assistance of refining executives in the compilation of adequate standardized records for the petroleum industry. 2. The balance of the report and the recommendation for an investi gation of the epidemiology of cancer in other industries lack definition necessary for a critical review; however, in principle, the meabere deem it unwise for the American Petroleum Institute to Initiate such a project. It seems unnecessary to recite the many difficult problems incidental to such an undertaking. For your information, the aei&ers of the Subcommittee on Carcinogenicity of the Medical Advisory Comulttee, by letter ballot in Septeaber 1932/ expressed considerable doubt as to the wisdom of extending to employees of customers the epidemiological studies of cancer by the Kettering Laboratory under the sponsor ship of the Amurlcmn Petroleum Institute. On behalf of members of the Medical Advisory Comittee, I express my sincere appreciation for the interest shown by members of the Study Committee end its Working Group in this subject, Very truly yours, ec: To Menbers Medical Advisory Committee E. Kern Linder, M. D Chairman, Medical Advisory Committee API 05564 . 5. - 5 - discernible but it was not anticipated that any such trends would be discernible prior to at least 5 years experience. It is hoped that the support which the General Committee, Division of Refining has given to the epidemiological study will stimulate renewed reporting of the cases with sufficient medical and occupational histories to permit some early correlations to be made about 19 5^. 1 "US uSi SaJ-f z'-'1 Summary 1. The RP (MC-l) Advisory Committee believes that the Kettering Laboratory is performing important work in the field of carcinogenesis of refinery streams and materials. They believe that although a great many practical answers have already been obtained, the work should be pursued because the work of the laboratory promises to provide many fundamental answers to questions which now exist concerning industrial and occupational carcinogenesis. 2. It is believed that the work with non-accelerating solvents which relates the carcinogenic responses of a solution of pure carcinogen to the dose applied per unit area per week to the skin is of extreme fundamental importance. The Committee urges that additional work be conducted to establish firmly the curve which expresses this relationship. 3. It is also believed that the work with accelerating solvents is also of extreme fundamental importance and that this should be pursued vigorously in an attempt to develop a complete understanding of the relative role of carcinogens and accelerators in refinery streams and materials. k. Since much of the correlation of chemical analyses with biological potency is dependent upon the accuracy of values, the Com mittee laments the fact that many of the Pj^j values thus far reported are based on data which the laboratory recognizes as not having been obtained . from the best biological experiment possible. The Committee suggests, there fore, that the laboratory devote considerable effort to repeating those experiments in an effort to develop Pj values that are based on the soundest possible biological experiment. j 5. The Committee believes that the work with washing techniques ! and protective creams may provide intensely practical guides to refinery : hygiene practice and suggests that this work be pursued as new approaches . appear to the laboratory. 6. The Committee recognizes that the epidemiological studies cannot he expected to produce significant results until at least 1956, and, therefore, . urges that renewed efforts at adequate case and occupational history reporting | be made during the next several years. It believes that adequate medical staffs can do most to insure the success of this program, and in this connection ; it acknowledges the stimulus that the General Committee, Division of Refining j has given to the attainment of this objective. 7. The laboratory has already determined that a number of refinery streams and materials have a relatively high degree of carcinogenicity. Although data obtained with mice cannot be directly transposed to humans, there is sufficient data in occupational cancer experience to indicate that the API 05728 /paa/A 1 C ^ jo p i X'jt r r ! / ESSO LABORATORIES l STANDARD OIL DEVELOPMENT COMPANY P. 0. BCK 51 LINDEN, N. J. January 26, 195^ The Members of the Medical Advisory Committee I as attaching a copy of a manuscript of a paper vhich Dr. A. Wesley Eorton vlshes to submit to the Journal of Analytical Chemistry In the near future. This paper was presented to the RPA Committee at Its meeting In Cincinnati on January 21, 195U. Certain minor modifications vere made at that time, and these modifications have been incorporated Into the attached manuscript, the revised copy having been received In my office on January 25, 195*1* It vas the unanimous agree ment of those of the RPA Committee present In Cincinnati (Dr. L. C. Beard and Dr. C. E. Eine vere absent) that this manuscript vas acceptable for publication. I would greatly appreciate it if each of you would review this manuscript in detail and transmit any criticisms or suggestions vhich you may have concerning it to Mr. Stroop vithln the next 20 days*. At the end of that time, if no major objections to the publication at this manuscript have been received from any of you, it is the plan to transmit It to the Eealth Committee of the Board for their approval. As you know, the total time for clearance of this manuscript is 60 days, at the end of vhich time Kettering Laboratory can submit this paper for publication, so that anything you can do to expedite comments would be greatly appreciated. Very truly yours, /a/ R, E. Eckardt REE;ilk Attachment B. E. ECKARDT, M. D. * Hots by D. V. Stroop As we have been delayed in transmitting this letter until February 3< ve shall deftr reference to Medical and Eealth Committee at the Board until March 1. Three copies of manuscript art enclosed for each connittee mesfcer. None is being sent to any technical advisor. DVS API Copy From D. V. Stroop For Information of Members of Medical Advisory p^wm-ittee and Subcommittee on Carcinogenicity May 6,195* ESSO LABORATORIES STANDARD OIL DEVELOPMENT CCMPANY P. 0. BOX 51> LINDEN, N. J. May k, 195U TO: Members of the Subcommittee on Carcinogenicity Gentlemen: I am attaching a copy of a manuscript forwarded to me by Dr. Eorton entitled "Carcinogenesis of the Skin: I. Basic Methods Employed in Testing Complex Hydrocarbon Type Tars and Oils, and the Development of a Quantitative Scale to Express Their Relative potencies to Mice". This paper has been written by Dr. Horton and his associate, Dorothy T. Denman. It is his plan, I believe, to submit this paper to Cancer Research for publication, although he has not yet indicated to me Just to which Journal he plans to submit it for publication. Dr. Horton has indicated that any date in May except the period May 11-20 would be all right for a meeting of the Subcommittee. After having reviewed the manuscript, I believe a meeting of the Subcommittee with Dr. Horton would be advisable, and would suggest that this sieeting be held after each of you has had ample time to review the manuscript both personally and possibly with some of your technical people, so that at the time of the meeting with Dr. Horton ve will be in a position to express all suggestions to him. With this in mind I tentatively propose the dates of Friday and Saturday, May 21 and 22, or Thursday and Friday, May 27 and 28 for a meeting with the Kettering group to discuss this manuscript. I would appreciate it If each of you would let me know as soon as possible which of these two dates would be satisfactory so that final arrange ments can be made with the Kettering group. As soon as your wishes are in, I shall send you definite notice of the meeting dates. Sincerely yours, /s/ R. E. Eckardt REE:ilk R. E. ECKARDT, M. D. cc: Members of the Medical Advisory Committee Dr. A. Wesley Horton API 05770 l> y I . I I .V v. ESSO LABORATORIES S T A N D A R D Of DEVELOPMENT COMPANY P O. BOX SI, LINDEN, N.J. MEDICAL RESEARCH DIVISION _ - R T E. E C K A R O T P H O MD DIRECTOR rc i A C W G E R A R D EHEPA DH DT O, X IMC OOL O G IS T INDUSTRIAL HYGIENE SECTION N A T H A N V. H E N D R IC K S . CH HE AD OR SECTION F R A N K L I N W C H U R C H M S. SCORGE M. W ILK C N IN G . M.S. INDUSTRIAL HYOlENISTS j 13* U ft 3 'HucisO M Or* Ooors H* OOl , , 26 > n i % I M c Iw M i a*. ^ 6cudbb f um steaMte r nam-- immr ta* teuai t e te a far t e a teof t, et eA qTI. 'afidSsl af f tle aw--A rIlawtei ,t Sela r t e Sa1JrtS*tw6et.aeteWprtLaieri itlifTftnaetetetleaaltaernt iitaetaela*uarwttifJitaS6p!tAper"teitakleertateUuArTfamItrMetat"e*fM*alaryttt1eee, l S t e 30, A t e i# t e t e e l S r * V te nx i fUihni maaddirt I Skia A Chairaai of t e of t e . la tlae 1krWlaflfatfrtltlea* tef te a fit w b far tear 1# US? te a J8f 19S6. Steiiaaarlrottel r*tte1t1etaert&a maa vtieli Z reepeetfwlly teriLi te RZEiilk -- R. S. KURET, X. Dp k LSVfert-i R, A. Kobo 3. . 3tep ^ API 05888 I t - u- 2. Epidemiology It was early recognised by the Subcommittee on Carcinogenicity that the chemical and biological work outlined above would give only a partial answer. It was expected that the epidemiological work would develop informa tion on the following two questions. . a. Does work in the petroleum industry or at any specific job within the petroleum industry subject the worker to an Increased risk of developing cancer? b. Have newer refilling processes, such as catalytic cracking, or increased severity of thermal cracking introduced any new risks of developing cancer to any segment of the petroleum workers? It is in general these newer processes which hare been shown to produce materials which have a high degree of carcinogenicity, to mice. J ''A central registry far the reporting of cancer cases occurring in the petroleum industry represented by the participating companies of the API was established at the Kettering Laboratory under the direction of Dr. Phair. In addition to reporting such eases, it was deemed essential that a complete occupational history for each ease also be reported so that correlations with occupation could be made. In the course of setting up this registry, it soon became apparent to Dr. Phair that the medical departments and medical records of some petroleum companies were Inadequate to permit accurate reporting of cancer cases. Ini tially, therefore, Dr. Phair'a major effort was in assisting medical directors, or refinery managers idler# medical directors were unavailable, in organising their departments and/or records so that good ease reports and occupational histories would be received in his office. Therefore, it has only been in the past year or two that an approach to effective reporting of all types of cancer cases and occupational histories has been achieved. Despite Incomplete uni formity of reporting and participation, ovar 1,300 cancer cases have been reported to Dr. Phair from 25 ocaqpaniea, and are in the process of statistical analysis. It is believed that worthwhile statistical analysis of these cases will require maintenance of this registry for a minimum of 6 years. In the interim, Dr. Phair continues to act In an advisory capacity to the petroleum coapanies and their medical directors for the collection and reporting of these cases. API 05892 - 7 - Salarles Miscellaneous Erp. Animals Supplies Travel Overhead $ 1,250 5.000 11.000 io,75o Composition of Subcommittee R. E. Eckardt, M. 0., Chairman Standard Oil Development Con?)any E. V* Adams Standard Oil Company (Indiana) L. C. Beard, Jr. Soeony-Vacun* Oil Company, Ine. Allan E. Dooley The Texas Company 7. D. Qasssmy, M. D. Gulf Oil Corporation L. M. Henderson The Pure Oil Company fit ' C. H. Hine, M. D. Shell Development Cos?)any E. K. Linder, M. D. The Atlantic Refining Company R. C. Kithoff California Research Corporation M. H. Hewquist, M. D. The Texas Company $14,000 21,000 $ 65,000 API 05895 UAhdtuJ &J C&is' >4 E S S O L A B O R A T O R I E S u sta n d a rd ol developm ent com pany P.O . BOX 51, LINDEN, N. J. MEDICAL RESEARCH DIVISION _o Be b t e eckarot . PH o . m d DIRECTOR ,,,,R A C E W GERARDE PH D . M D * HEAD TOXICOLOGIST rial? 16, 1951* INDUSTRIAL HYGIENE SECTION Na t h a n v . h e n d r ic k s . Ch e HEAD O r SECTION F R A N K L I N W . C H U R C H . M S. GEORGE M. W IL K E N IN G . M .s. INDUSTRIAL HYGIENISTS y. Lm baia Stm Stenderti d i Oe*an? 15 -- t 5lat Street lev Zerk 19, le v Toark Star ft. badai Twr o-- ta e e o s e n l* th flr v t p a ra *r*h of . Berteli' t e Klae O nvn'a paper oa , Carinetenttl^ ef th S tia I . * bea erveted a votia lia rte la -- ent sf i i -- nt nei m veveaTirr Tbere 1 apparenti? alee eeae aeaaara abevt hev jear n a a irti a be reecl t ei v it i th la t t a r i* Libarter?. de aaueatlea la tb at tbe la e t eaateaee e f th ia paragrafa bave th pfaraae ate alee* e tte * ea th t e e f l t . l i th ia ha* vemli m n m th eb>etlane fate pee beve te tb ia peragnpb, I m aere tbat tbe la t t a r i* te rra ia r? m a li be -- u rtili te tb le alaer eh-- . I f th rtbetv ebaac* te a net avtiaf? tbe ebjeetleav Mah | t i beve te tb ia peragnpb, l t eevlil be * ve* vtle tfeaft ym re e rlte tbe flr v t p a tp tp h aa jm veld v lA te -- l t verde* t e tbat yea a t e lt tb ia r-- r i t i * te . 1-- riera idth a aarbea ap? te Br. te s e ( . Bertea) te m i f th la t t a r i* Ubarvi ar ? vali be f i l a abla te re v ritU c tbe flr v t paragrafi ea jrae v a te te i t -- vrlttaa. m tbe w est tb at tbe la t t a r i* L A v r t i iy veel* aet * ree te yver re a rlte , l t veald tbea -- esr te ae tb at te a tb ia pepar la -- a rt e te tbe a te tte e e f tbe Beard p rle r te pvbl la a tte , a evi* te a m a t e , aa tbe Meritati brirlaar? either tbat tba la t t a r i* preferable te tb a t. f a t i 1e li? , tba avi te i -- v ltb tbe Xebee t e etbare et tbe B e tte r!* oaeiiarafcla tb a *b t te tb ia l f Ita * ef that nef-- ed tp tba Bevi reaaeaa far a t e r l* te tb te v a te tte b e la a ef tbe, BIebetme liwn entbnant , te tb slr ivleealtrie(*IteOr. verri!* Initeari ie ter? atre* I atteapteri te rilweee tbia vltb pia aa tbe telette teda?* het alaee ?eu vere est ef j -- r e fflae 1 tb a *b t I t eeald be handled b? v a li, eluse Z ea f a i* oa * , tw e tlaa a t e r tl* ea the 17th t e v ili be eet e f tbe e ffla e fa r tee wake. Z | v a te be happ? ta -- i th is farth er i f ym fe e l i t aeeeeser? a fte r Z retare I tr m a? tveafcien t e I f i t bea net alreari? beaa aettZed la the aaenfelaa. i Slneerel? yeara, KZEillk jr. Q. K. Savodera^ a. L. SCIARJf, M. D. API 05899 V V J 17 6, 195* Dr. O N ri* S tttM n , Chairvaa Madle*l kpd^rj Oaaadttaa Aaoriaap^fatrola* In a tita t* 50 Wwt 5Ctfe StTM t priorie, X*v Tark .* Omt Dvator Seeederei Or. l i M t M ai m Mygr * f Ila la tta r W Mr. Straap tonoormIftg ih * propoaa i pohliaatlaa bp . fa ri-- u i U n Oaahaa ratard laf oaralaofam ala a f tba afcia. baat af ito eeggeatlw va bava aaia bava bava praparlj raaogalai. Va ara tiU a f tba plalaa tbat tba apaniac paracrapb la ala i firn u aai la a irla t baapUf v ltb ha fia ta a f tba lta a tie a . Ornili aaah tla a aa a a fla ita ai talami varrai*tlca baa bava aatabllabad batiiaaa f i a g i ta h i# badila aroM ila fbaoUaaa aai tba aaaarranea a f akla aaaaar, X b a liMa bava aalaal tata ara a a lj aaggaatlr*. Xt la a f v a ia ra iia ila t hai . la rta a ta * w r r r la l a f ib i* rarag raj*. I f a aa ali ha ara hai tba a a ta trtg t 111 taf la r tr ia tly prafaaalaaal baaaala, hia ah>atlaaa ara a ll ta b i. Tra* paat parlano*. banaoar, 1 M raaaaaabiy aara tb at bla n a itila w w t ba r a lla i apoa ta p ra ta a ^ p fbaa aagaa! fi a i apla* raia tla a * probiaa*. Tary t r a i/ jaara, D/tJak aoi Or. R. I . Baharit Rr. W illiam la ia a Mr. D. 7. Stroop LIO VXDS, X. D. API 05900 S>CLr'.''K 4 I THE REPORT OF THE SUBCOMMITTEE ON CARCINOGENICITY TO THE MEDICAL ADVISORY COMMITTEE OF THE API The Subcommittee on Carcinogenicity of the API Medical Advisory Committee, one of the first subcommittees created, was established early in 19^5. It was formed after it became known that certain petroleum oils and fractions had been demonstrated to possess fluorescence similar to certain known carcinogens, and, when painted on mice, produced tumors and cancers. Negotiations were then begun between this Subcommittee and Dr. Kehoe of the Kettering Laboratory which culminated, early in 19^6, in an agreement between the API and the University of Cincinnati, under which the Kettering Laboratory of Applied Physiology would "investigate the toxi city and mode of action of certain petroleum products." The investigation began with the testing of 8 oils supplied by three participating companies, in addition to negative controls of water and white oil and positive controls of methylcholanthrene. Of the 8 oils tested, only 2 produced skin tumors in mice. One of these was an unflashed thermal residue, the other a clarified oil. These investigations were carried out at a cost of $6,000, and were reported in detail to the Sub committee b y the Kettering Laboratory on November 5> 19^6* However, when the results were becoming apparent early in 19W , the Medical Advisory Committee, on the advice of the Subcommittee on Carcinogenicity, forwarded to the members of the Safety Committee of the Board of Directors of the API a resolution dated April 5, 19^8. This resolution called upon the Executive Committee of the Board of Directors "to establish a comprehensive research project for the development of fundamental facts, analytical techniques and related information pertain ing to cancer-causing compounds which may occur in petroleum or be produced therefrom." This resolution called for the solicitation of contributions to a special research fund in the amount of $110,000 for the first year, of which $ 50,000 would be a non-recurring capital expenditure for construc tion of extraordinary experimental facilities at the Kettering laboratory. This resolution was presumably approved by the Executive Committee and on July 1, 1 9 W a check in the amount of $65,000 was sent to the Kettering Laboratory, $k0,000 of this amount as a grant for animal quarters. With the expansion of this research project in 19^8, A. W. Horton, Ph. D. was added to the staff of the Kettering Laboratory to supervise the chemical and biological work on petroleum and petroleum fractions, and the services of J. J. Phair, M. D., Professor of Preventive Medicine, University of Cincinnati, College of Medicine, were made available to the staff to develop and supervise an epidemiological survey of the incidence of cancer in the petroleum industry. From this point on, the research project can be divided into two phases, namely (l) the chemical and biological work, and (2) the epidemiology. API 05913