Document B50dOQdvjmEMVop86JbnMbzZ8

Castleman File: American Petroleum Institute w/c = with cover letter or memo If DATE = 0, undated CD-ROM Document #:API ^ y DATE __ published article from trade journal __ published advertisements __ newspaper article __ published government report __ government inspection results __ unpublished or internal report __ unpublished presentation from conference __ letter __ memorandum __ industry warning labels __ industry sales literature __ ipdustry recommended practices meeting minutes (with attachments) __ membership list BC notes J^rHATI It. OHIO UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH January 12, 1950 CABLE ADDRESS: ECTLAI. CINCINNATI TELEPHONE: CAPITOL UI4 Mr. D. V. Stroop, American Petroleum Institute, 50 West 50th Street, New York City 20. Dear Mr. Stroop: I herewith acknowledge with thanks receipt of American Petroleum Institute's check in the amount of $59,965.39, covering expenditures to he made on their behalf for the balance of the year ending June 30, 1950. Very truly yours, Dr. Kehoe Jaaaarj 10, 1950 Dr. RoWart A. Sake* Kattarlaf Lakerotary ef AyfUat ftyalolaKy Colla^a of Mallolaa tfcdwalt? of Clwrf--tl ClnMmatL 19, Ofcla Saar fioetor IMaaos agri--it of tka SlttSta^TS^ok la tka -amt of $38,963*39 to amtima tka laroatl*atioi of tka toxicity Hi reta af aatlao at aortal* yokrnla-- jrotaats for tka flawia of tka |ar oailag Jam 30, 1930. Tka fW0 of 8)8,963.39 la tka tlttaarama kataaoa tka tolaw of $49,kit.00 itiWi la tka icrwaast aod tka $10,448.61 wiyaiil to1 ana aa of kaa 30, 1969. Tory truly jama, MBit UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH ,|TTERIne LABORATORY "lO|1lL1,r*E OF MEDICINE--EDEN H. OHIO AVENUE 9 CAftLE ADORESS. RET LAB CINCINNATI TELEPHONE. CAPITOL 1414 # Che American Fetrcleun Inst ^ Vest Street, liev rcrk City 2o. ute, ' \/ / year Mr. Strocp: I an sending ycu herewith, for your information, a statement c: expenditures made on behalf of She American Petroleum Institute ter the fourth quarter of lyAx. If you have any questions or comments, doctor Kehoe would appreciate your bringing them to not very truly yours, a* zZIC . E . r.. F or tlage , Dr. Kehoe ;-etar tc API 04919 UNIVERSITY OF CINCINNATI KETTERING LABORATORY ACCOUNT Or AMERICAN PETROLEUM INSTITUTE For the fourth Quarter 1949 ^ES (Base: on Proportion of Time Actually Spent on Project) Robert A. Kehoe - Supervision Francis Heyroth - Chemical and Toxicological Asst. Frank Dutra - Pathological Assistance Frank Cleveland " " A. Wesley Horton - Chemical Assistance John Phair . Dorothy Templeton-a " " Russell Tye -" " Karl Korpi - Technical Assistance Sylvan Witherup " " Ruth Pierle "" Waldo Younker "" Harold Schlecht " ? 17.30 33.37 14.01 33.56 1800.00 1375*02 303.54 900.00 135.54 160.35 1125.00 47.86 7.78 6013.33 rTTLLANEQUS EXPENSE purchase of Animals 119.21 Laboratory Supplies 328.37 Traveling Expense . 1194.02 Proportion of Secretarial, Library, Janitors, Wash Boys, Draftsman, Shipping Clerks, Animal Caretakers, Histopathological Preparation etc ............................ 2598.32 Proportion of Heat, Gas, Electricity, Steam, Telephone, Maintenance, Pensions, Annuities etc ..................... 2378. TOTAL $12,631. 63 Balance Available for Work in 1949 at End of 3rd Quarter 1949 .......................................... $47*225*78 Expenditures 4th Quarter 1949 ................................. 12,631.63 Balance Available for Work in 1950 at End of 4th Quarter............................................... 34,594.15 OFFICE of the assistant TO THE PRESIDENT HARVARD UNIVERSITY March 6, 1950 24 Milk Street Boston g, Massachusetts Mr. David V. Stroup, Director American Petroleum Institute 50 Vest 50th Street New York 20, N.Y. Dear Mr. Stroup: Ve are pleased to enclose Harvard's formal acknowledgment for your valued assistance in the matter of the grant to the Department of Industrial Hygiene. As you requested, I return two copies of the letter of authorization duly accepted on behalf of Harvard. Sincerely yours EGKJr/S API 04921 ENT OF SAFETY pAoV*flAPRTMv stroop. Director American Petroleum Institute SO WEST SOTH STREET NEW YORK 20. N. Y. as, 1990 * Milk Mr--t tatoa*, taa. t. tar task la Mm ata af ta.0M la mmlamL. rn #MM JO, 1990 ta jra>at la to taataato. to f tat tato a taint af ta --at wjatoii ato ta tola--a la ta faaA will to wMawi, to laaaj Valtor, Inritoy, tarlaaa htril-- Xaatltoto, 9* tat 3to Start, ta lark m, ta fark. 3. tala It la art aatlalfatoA tat yatwtoli talspaata will arlaa aat rf tola jra>*t, it la waiaratoM ato uni tat If saak afcaaU arlaa, ta toaaflto will to IrAlaatoO to ta ptolla to jaMlaatlaa ar attorwlaa. 04922 API American Petroleum Institute SO WEST SOTM STREET NEW YORK 20, N. Y. -rMENT of safety stroop. director Irtrwtty *8, 1950 Mr. U. Baskall Croeksr larvate Ualvsralty 2k Milk attest lostom 9, Mem. tear Ik*. Crockar: All latter 1a aatharltetloa ta etlw tea lavastlgatlon of psralsalhls eoaaoatratlaas of tesla sahstaacos, lawi aa Aasrleaa Nttolm Iaatltata Maileal Yrojoet Mb. 2j frofsaser Philip Srlakar, Mrastor, u plaaaait ate adalBlstorte cooparatlvalj vlte tea teni--itte* oa Psralsalhls Caaaatetetloaa of tea All Msdleal Uriaerr Cotelttaa, trm March 15, 1950 to Jim 30, 1950, aat>et to tea follovlag eoteltlaaa: 1. te4#at Malarias ate Ixysaass $3^00 2. ter shook la tea aaoot of *3,000 la awlaaad. 0b Jibs 30, 1950 tea project is to tsmdaats. Aa of teat data a atataaaat of tea aanaat sspatead ate tea telaaea la tea fate vlll ha roaAarte to Laos? Valkar, Saoratarj, AMrlaoa tetralaaa Iaatltata, 50 teat 50te Otrsot, lav Tork 20, tev 1M. 3. wsiia it la aet aatUljataA teat pataatahls dsTslojasaia vlll arias oat of this project, it la aaAarstooA ate agraad that If aaah ahoolA arias, tea hoaaflte aill ha dedicated to tea pills hj pahllaatlaa or otherwise. tery traly jaara. Accepted hy: Prealdeat C tellaaa of Prsold API 04923 TRA<ta iV aiv ! ?.3 /abte're'^ir/e.jk'r&te ,di/ie^spra/t/ud&/r t American Petroleum Institute ^or^Le'^en^rouJ three thousand dollars on account of a enewed grant to continue investigation of permissible concentrations of toxic substances, under the direction of Pro fessor Philio Irinker. "1 x-iarch 6, ItJO API 04924 Jtitamrf 28, 1950 tTu. In, i. I, Mt 04925 APX Iktllf * 30, If* 1* S. I) 13, 19* * it #3^00 , 5* Wk ttlMfl -MilirtH tkt Irtwkto rtjr Mnyt|^UU wtorgM* API 04926 ea^ireik) /Ch^cr^ra-ucicfC^A American Petroleum Institute ten thousand dollars in continued support of investigation of permis sible concentrations of toxic sub stances under the direction of Dr. Philip Drinker, as stated in their letter dated March li^, 1914.9 to Mr. Claflin. Recording Secretary March 17, 1949 OFFICE of special adviser TO THE PRESIDENT HARVARD UNIVERSITY March 17, 1949 24 Milk Street Boston 9, Massachusetts Mr. David V. Stroop,Director Department of Safety American Petroleum Institute 50 Vest 50th Street New York 20, N.Y. Dear Mr. Stroop: This will acknowledge receipt of the letter of March 14 from the American Petroleum Institute to Mr. Claflin, who resigned as Treasurer last June 30. I take pleasure in enclosing herewith our formal acknowledgment for the very welcome gift of $10,000 for the continuation of the investigation which is being carried on under the direction of Dr. Philip Drinker. Ve are indeed grateful to the American Petroleum Institute for this additional assistance. I also return herewith two copies of the letter setting forth the conditions on which this project is being undertaken. I have indicated Harvard's acceptance by signing this letter as Assistant Secretary. Sincerely yours. U. Haskell Crocker Recording Secretary S API 04928 American Petroleum Institute 50 WEST SOth STREET NEW YORK 20. N. Y. ISTMENT or SAFETY pEp*v fTROOF. DIRECTOR I `V,B ' *. Vllllm I. Clwflis, ir. i ft MLlk Itewt 1*, 19*9 Clsfllai I Ski* letter Is --thw1.wtlsa tistli tt> lVMtlirtla IiMm Ihstltsts Mini ftvjMt Ss. tj Trwtnmcr IhUly Mtar, Blrweter, as flsswA as* iWlitril --frettra!/ with ths Ihtaltlii m taftsslhl* C--trwtl-- sf the X mtiml Uxiaarj Cwlttss, trm M 15, 19*9 ts Mrwh it, 2990, *>st ts the faUswlas iltl--i U HAS''-'.'- Assi'-^s-.t Bfc - j. w - -- > API 04929 American Petroleum Institute 50 WEST SOth STREET NEW YORK 20. N. Y. ^.sTMCNT OF SAFETY v sthOOP. DmecTo* B`VIB me. 1111: I. Claflia, Jr. of ltfurt ValTerolty 24 nil Street Mreh 14, 1949 Boar J*. Clafllai Thle letter Is motherleatlaa to onotlaee the larvotlpatlm of yanlMlUi of toxlo oahstoanoo, kaooi as I--tIcoh fetralom Xootltate Mlotl frojeet Bo. tj ftrfimr fhlUf ftrlatar, Diroetor, u pi sand aad adalalstared eooyoratltaly vlth tie aabeoMittoo m loraiaalkle C--wrtwttcw of the JPI Medical Adriaory CoMlttee, frta Marsh 1?, 1949 to Mroh 14, 1990, sehject to the folleviag eoadltloaa: 1. ladot^^ ^ ^ 2. Oor shook la the mmmk of $10,000 is --Insol. As of Mreh 14, 1950,.a shaft of o,od siylil ad the halaaoo la the tmi till ho roadwo i to Lossy Whiter, doorstory, I-- loon Petrelesa testltxte, 5ttfc4*ot, JwrlorkftO, *.I. 3. If the mark water this prejoet aheald tanlaote oa or hoforo Mwah lk, 1950, It Is OtHiiI that aay i^dot halaaee la the fai till ho rota ait to the loot!tato. Zf the seek is to ho coatlaved oa aad after Mweh 15, 1950, aay awriiadil holoaoe la tte food shall heeeao atallahlo for oat ho added to da Mat for the 4. While It Is aot aatloljatod that yatoatahlo tmloputo sill artos oat at this projoot. It is Marat mid aad agreed that it sash ohoald arise, 4h haaaflhaalll ho *odlooted to the jahlle hy jahlleatloa Kory traly years. Aeoepted hy: President aad Believe of HIUKD CUB, hy Qjosu. r * ^pcl :-,tR^*-ecr' '~r API 04930 March It, 19*9 Profsaacr Philip Brlakar li*r*rd Vnlrmitj School of Pu^llo laalth 55 ShattrcP Ftsrsrt Boston 15, Nua. Dear Profaaacr Drlakar: Vs har* bam Aalajud In tha nagotiatioo of oar continuing agrsiwnt an Medical Protect Bo. 2; therefore, as srs encloelng both the letter of authorisation (3 copJae) wl otcr check 1a ths woant af $10,000. Vs treat that both ars In good fen sad accept able to pou and ths TreaearsT of Bkrrard TXoloarslty. If, os, and atan accepted, plsans rsturu too signed eoplee of the letter for oar ass and fllao. Tsry truly yours, OT5:d Encloearec cc: IT. T. C. Baird Dr. k. S. Boag Dr. J. P. Holt API 04931 prefT1 the oftfi!ce ot DAVID V. STROOP \X' T.JW- T<eAS_ ta*sf C-*-rs>(*,^a o f=- -^-wiS> <A- SCS.C-I&-NnB-KfT wHltvi CjasVeJC.& CjerJT\KJUft-TIOvJ OP- M&DlCiJU. f'k&v/ieUSuX APPl?e^ecJ g/ 357< E-C-U-nve. frtJD t^iwaWced spe^>Ri- p--UI iNwftOn's CawTCH&<jTt=Q5 i sJ l^hi- API 04932 {/Jr- il&o Mr. Billion 1. Clan la, Jte. 9k Milk Btroot 4 j,^ Mr. CUnint This lottar i> Htkerlati to of yaxnloalhlo ecnooBtratloaa of toaclo VitnlMi institute Modlool frojwt Bo. 2) nail oopntulvmal?if vnlatt tho o tlOBO of Iho dFX MHL&ool Advisory / P; W, oh-lt, 1950, sshjoot to tho yr . 1. 2lOQ>o _ f. Otf shock la tho Mwah lhjr^g^o otot--wit oftho S bo thP fBDi till ho noteti tO liMf hi --r, nwiwij, PoiroLotai institute*. $0 Boot 9>tfc Btrost, Bov York SO, B.Y. / %S ITteo vcrk vador thlo jrojoet should tarnlaate on or toforo Mwohlhy-lty, it,i> understood that any tbospondad/WLsaoo la tho fond Vill ho roUraod' tfa tho Institute. IT tho vork V to bs f on oai aftor hrA 15, 1950* asyuayrtlod^ia,luapoli atnilahla^r and tended te'tltfWt for tho z/ k, Vkllo it io not aatlelyatod that yataatehlo vlll arioo oat of this projoot, it is v*arstood and arood that if should arioo, tho tonofita vlll ho dodieatod to tho ptihllo hy pnhlloatl Bory truly yours. *7. Asooptod hjt Prooldoet and Ballous of nuniKD cnrjjni, hy ''API 04933 Fcr Infcrmaticn Only - N ) AMERICAN PETROLEUM INSTITUTE SUBCOMMITTEE C-N CARCINOGENICITY Minutes cf Meeting March 25, i?5C Kettering laboratory College of Medicine University cf Cincinnati Cincinnati, Ohio \V u Members Present MeTver Woody (Chairman) Marshall Clinton T. M. Frank A. S. Hoag J. P. Holt (Rep. by R. E. Eckardt) T. J. Kelly J. V. Long M. N. Newquist Associates Present L. C. Beard, Jr. L. C. Crockett R. M. Lar.don E. ?. Lankelma K. G. Mackenzie R. M. Shepardson Visitors T. E. Allen F. F. Boys J. W. Crookshank Kieffer Davis E. K. Linder B. B. Peeve E. V. Adams R. D. Bent R. C. Cole T. E. DeVilliers L. M. Henderson Guests Lewis J. Cralley - U. S. Public Health Service Francis Heyroth - University of Cincinnati A. W. Horton - University of Cincinnati R. A. Kehoe - University of Cincinnati John J. Phair - University of Cincinnati D. V. Stroop - American Petroleum Institute J. G. Townsend - U. S. Public Eealth Service K. R. Warrick - The Texas Company Members Absent L. H. Curtis W. R. Levis Chas. A. Swan Associates Absent R. W. Faulk H. G. M. Fischer Allen E. Dooley ) TEE KZTTZF INC IA3CRAP-FY :? UWV Dr. Robert A. Kehoe, Director, well :med the members and guests and jive them an historical review cf the oris; : and growth of the Kettering L a'., oratory. He expressed appreciation for the contribution of capital funds made by the petroleum industry and described the facilities which had been made possible by those funds. He mentioned the types of industrial problems which are studied at the laboratory and reviewed in detail those problems which are under investigation for the petroleum industry. He emphasized the exceptional character of the -.PI project on carcinogenicity because it constitutes an organized study of a problem prior to the occurrence cf trouble. Usually the trouble occurs before any investigation is made. PROGRESS REPORT 1. Dr. A. Wesley Horten presented and discussed his report of March 15th, a copy of which is attached. 2. Dr. John J. Fhair discussed progress and plans being made on the epidemiological studies for the project. See attached copy of Dr. Pharr's report. 3. For the information of those present, D. V. Stroop read draft of progress report which was in preparation for John R. Suman, Chairman of the Safety Committee of the Board of Directors, to present to the Board at its meeting to be held in Houston, Texas on April 2nd. A copy of the report as presented by Mr. Suman is attached. GUESTS Dr. Woody introduced Dr. J. G. Townsend, Chief, Division of Industrial Hygiene, Public Health Service, who reviewed the division's long experience with scrotal and other forms of cancer incidental to workers in wax-pressing operations. He reminded the members that the Public Health Service is r.ot empowered to control or regulate industrial operations; it can only suggest or recommend precautionary and remedial measures to improve industrial hygiene conditions. He called attention to the U. 3. Public Health laboratory in Cincinnati and tendered the services cf a liaison officer to work with Lr. Kehoe and to correlate plans so as to avoid duplication of work with that now be31jg conducted for the Bureau of Mines on shale oil. API 04935 He expressed his appreciation of the opportunity to attend the sectin 3-nd to obtain first-hand inforsacior. on the work being done by the industry at Kettering laboratory. Dr. Townsend introduced Dr. Cralley, who spoke briefly about his interest in the project. TCUP CF IABCjRATCFIZS Following a splendid luncheon served in the University of Cincinnati dining room, Drs. Kehoe and Heyroth conducted the members and guests on extended tours of inspection of the Kettering Laboratories. EXECUTIVE SESSION The members held a short executive session to discuss matters of business relating to the administration cf the carcinogenicity project. Approved: Mclver Woody, M.D. Chairman T. V. Stroop Acting Secretary a-lb-5C API 04936 Report tc Subcommittee cn Carcinogenicity of the API Medical .advisory Committee r S^Tl PROJECT OR CARCINOGENICITY AT TEE UNIVERSITY CF CINCINNATI Operating data on the various cracking and lube refining processes have been received from over 90 per cent of the cooperating oil companies. Collection of the samples listed in Table 1 is under way, the materials being held temporarily in storage at the refineries until A requested by the Kettering Laboratory for animal testing. Corresponding tc each of the product samples listed, a sample of the feed stock to the particular unit is being collected at the same time. Thus, if any one of the products is found to have unusual carcinogenic properties, it will be possible to go back and determine the potency cf the feed stream for a direct comparison. Up to the present time, spectral analysis has continued to prove a reliable tool for the prediction of the carcinogenic potency of the various petroleum products to which it has been applied. Accordingly, it has been requested that this procedure be applied to each of the product samples listed in Table 1 by the company collecting it. With all of the analytical and spectral absorption properties of the samples as well as the operating data on the units producing them before us, it will be possible tc select the materials for animal testing in such a way that complete coverage cf the various processes can be given ar.d, at the same time, the validity of the spectral method cf analysis for carcinogen concentration can be determined rioOrously. The latter is a ! most important point since without a reliable analytical tool it might be necessary to keep a large scale animal testing program going continuously for several years. This tentative sample list for the period, July 1950 to July 1951, is being submitted at this time for discussion and comments by the Members and Associates of the Medical Advisory Committee. shall welcome any suggestions as to its organization. The complete list of the samples which are under study at the present time will be included in cur April report which will be circulated in advance of the Chicago meeting. Doctor J. J. Phair will outline at that meeting the status cf hia epidemiological study. AWE;fe March 15, 1550 A.. Wesley Hcrtcn API 04937 TABLE 1 UNIT Heavy Gaa Oils Tars Gas OIL Cracking ViBCoaity Breaking Naphtha Reforming 5 3 Coking 4 Polyforming 1 Houdry TCC FCC Cyclovereion 5 6 12 2 Hydroformer Wax PreBeing Furfural Extraction Phenol Extraction Duosol Extraction Nitrobenzene Extraction TOTAL PRODUCT SAMPLES 148 VUD> 23 8 4 4 2 Synthetic Bottoms 8 17 PRODUCTS Slurry (Decanted Oil) Coke 4 10 Slack Wax 4 Press Oil , 2 Solvent Extracts 5 15 3 1 API / For Information Only - Not for Publication THE PROJECT ON CARCINOGENICITY PROPOSED EPIDEMIOLOGICAL STUDIES Objectives Possible Approaches Imp1ement atio n Preliminary Outline for The Subcommittee on Carcinogenicity of the API Medical Advisory Committee March 25 1950 API 04939 Tc determine as accurately as possible, the prevalence and incidence rates of retrograde, hypertrophic, and/or neoplastic responses in man following various degrees of exposure during production, processing, transportation and consumption to:A. petroleum products obtained by catalytic cracking processes. B. petroleum products obtained by thermal cracking processes. C. products encountered in wax extraction. D. special chemical products. E. various crude oils. To compare, insofar as possible, the prevalence and incidence rates found with similar rates of:A. groups of workers in the petroleum industry not directly in contact with petroleum or its products. B. groups not employed in the petroleum industry, such as;1. the general population a. of the nation. b. of the same geographic areas. 2. the employees of other industries a. of the nation. b. of the same geographic areas. f 2- t. To ascertain and evaluate, insofar as possible, the relative values of control procedures that are:A. accepted and employed at the present time by essentially the entire industry. B. recommended but not adopted or employed except by a few companies. C. additional measures which may become important during the course of this investigation. ;V. To recommend for consideration of all interested parties, employing the results of the laboratory and epidemiological studies, standardized safety and control procedures provided that:A. unusual incidence or prevalence rates are found justifying the control procedures. B. the measures increase the safety and it efficiency of the operation even though the rates might not indicate a significant hazard. U API 04941 -T / j- FC S3 ^ a-ffoaches Under this approach, the cooperating companies will forward to the University of Cincinnati ail available clinical and employment records of proven cr suspected cases of nooplastic disease v/hich have been reported among their employees during the past insofar as records are available. H, Current Registry V A. Clinical and Employment Record Study A central registry will be established by the University of Cincinnati group to receive reports of neoplastic disease as they are discovered by and/or reported currently to the various Medical Departments. With this plan, the various cooperating companies would submit a-fairly complete clinical report and an adequate employment record using standardized record forms. These records can be expected to be somewhat more reliable than those forwarded under the Historical Approach, since they would be completed immediately upon the report of a case. 3. Central Pathology Service As an adjunct to the central registry, it would seem desirable to plan for the establishment of a central pathology service so that a uniform tissue diagnosis would be available both for the study purposes and to stimulate the interest and cooperation of the various Medical Departments. API 04942 v - \n ; . Hmplcyee Health Record Study In this investigation the epidemiological team of the University of Cincinnati would attempt a review of the employee health benefit records,not only cf the various companies of the petroleum industry but certain other cooperating industries, to establish, insofar as possible, comparable incidence rates for all diseases. This approach, with due regard for the many variables, should develop certain useful intra- and extra-mural comparisons, jy. Dermatological Field Study This plan envisions field studies among various groups if of workers employed not only in the petroleum industry but also in other industries with the objective of establishing comparable incidence rates for retrograde or hyperkeratctic lesions on the exposed skin surfaces. The groups to be surveyed by a trained team from the University of Cincinnati should be selected by an authorized committee familiar with all the possible variables and capable of securing adequatecooperation bi all interested groups. These rates, if seme I! degree of correlation is shown, could be used to determine susceptibility of individuals or groups, to estimate the degree of hazard in various situations and to evaluate control procedures that may be proposed. V. Slack Wax Study An investigation by one cf the interested members cf this group has pointed cut an unusual hazard in their slack wax process. In view of this finding, it would be desirabl? for the survey group of the University of Cincinnati, working either independently or with some other company and/or companies, to repeat this investigation. API 04943 _ e_ rv :t ^ mto v / Historical Approach This approach was approved in principle at the November, IQlxb meeting of the Medical Advisory Committee following the report of the Subcommittee. Actual v/crk was held up until the various Medical Directors and Technical Advisors could be contacted individually for their suggestions regarding the clinical and employment records to be employed. It was necessary also to determine legal right of the various Medical Departments to release clinical records of their employees to an independent agency. These questions have been fully clarified, and the new record forms embodying the various suggestions are being drafted. The proposed handling of the individual records so that the Medical Departments will not incur a liability because of their release to an independent agency with the standard records will be included in the formal report to be made at the April meeting in Chicago. Current Registry A. Clinical and employment Record Study Since the records and questions involved under this plan are very similar to those found with the Historical Approach, this effort has likewise awaited completion of one various interviews, although the concept was approved in principle at the November meeting. It is hoped that this work car. begin early this summer. API 04944 -T I i 9 XI* Current Registry (Cent.) B. Central Pathology Service This is a new venture and one that is favored by many cf the Medical Directors. Before it can be placed into operation, however, vail be necessary to determine if all believe that it is desirable and an acceptable method of financing. Employee Health Record Study This plan has been discussed only with a few of the Medical Directors. Before definitive action can be taken, this approach should be discussed thoroughly by the Medical Advisory Committee, since a great deal of effort will be required both from the various companies as well as the University of Cincinnati to bring it to a successful termination. IV. Dermatological Field Survey This, too, is a concept which has not been completely discussed and must be explored thoroughly by all interested parties, financing and staffing would be problems, but this sp proach could be tested thoroughly within a very short time. If proven valid, it should give answers to the proposed objectives much more quickly and easily than any other method. V. Slack Wax Study It is apparent now that the probable implementation of this approach will require the cooperation cf one cr two companies in the industry. If the Medical Advisory Committee approves and interested companies can be fonrjd, this investigation could get under way very shortly without too much trouble. API 04945 SAFETY COMMITTEE CF BCAP.r OF DIRECTORS REPOST OF CHAIRMAN - JESS' R. SUMAN Concurrently with important developments in refining methods, processes, and products, the industry's toxicological problems are growing in number and complexity. Oil companies are making substantial increases in their medical staffs and facilities. These developments led to the creation of the Institute's Medical Advisory Committee in 19^5- Since then the committc-e has served constructively by making useful information available to oil companies for their protection of employees and customers against accidental injury and for the defense of industry against unreasonable and unnecessary laws and regulations, as well as unjustified and false claims for damages. The organization of this committee and its semiannual meetings have facilitated an informal exchange of medical information of intangible but substantial value in the prevention and treatment of industrial injuries and occupational disease. The committee also has been instrumental in organizing special studies and investigations on important toxicological problems with coopera tive grants-in-aid at the University of Cincinnati and Harvard University. The initiation of this work promptly after the end of the war has placed the industry in a favorable position at a time when numerous proposals are being made to give government new and far-reaching controls in the field of industrial medicine and hygiene. The individual members of the committee, through their several professional channels and associations, acquire valuable informa tion regarding these trends in regulatory legislation. The pooling of the information thus obtained clearly indicates trends which arc disquieting. f Highlighted by the California snog problems and supplemented by the reports on the Dcnora situation, there is an active drive to depose on American Standard Code on Industrial Hygiene. This proposal is put forward 'ey the American Conference of Governmental Industrial Hygienists, which has drafted a code that is far from realistic and shows little sympathy for the- practical needs of industry. If adopted generally, such an arbitrary code would impose unreasonable and unnecessary restrictions upon industry, and might readily become the basis for state laws and regulations. Another indication of the growing interest of government is a letter recently received from the Chief, Division of Industrial Hygiene, Public Health Service. He suggested e meeting with the Medical Advisory Committee to discuss potential health hazards and possible control procedures in the petroleum industry. The committee has invited him to attend its regular mid-year meeting in April and has held some preliminary discussions with his representatives at a recent subcommittee meeting held at Kettering Laboratory in Cincinnati. Because of enforcement difficulties it may be safe to assume that statutory and regulatory control of industrial hygiene will be unreasonably restrictive and unnecessarily so for responsible and progressive companies which voluntarily are adopting policies to insure hygienic working conditions. It is encouraging to note the number of companic-9 which are adopting such progressive policies because it suggests the possibility of avoiding some or most statutory and regulatory controls. 3 -5C API 04947 f American Petroleum Institute 50 WEST 50th STREET NEW YORK 20. N. Y. April 11, 1950 To Members and Associates Subcommittee on Carcinogenicity Gentlemen: For your consideration in advance of your meet ing to be held April 23, there is enclosed copy of Doctor Horton's report on the Institute's carcinogenicity project at the University of Cincinnati, with copy of his letter dated April 7th. You will note that the report contains data which is to be published as provided for in the contract between the Institute and the University. Pursuant to action taken by the Executive Committee of the Board of Directors on November 10, 19^9* John R. Suman, Chairman, Safety Committee of the Board of Directors, has instructed me to send copies of this report to the members of the General Committee, Division of Refining. Copies of the report also are being sent to mem bers of the Safety Committee of the Board and to all mem bers and associates of the Medical Advisory Committee. Very truly yours, DVS :d Enclosures D. V. Stroop MC: Members, Safety Committee of the Board of Directors. Members, General Committee, Division of Refining. Members and Associates, Medical Advisory Committee. Mr. W. T. Gunn Dr. A. Wesley Horton (5 copies) API 04948 I c Oil COPY UNIVERSITY 0? CINCINNATI COP1: Department of Preventive Medicine and Industrial Health April 7, 1950 The Kettering Laboratory nclleSe of Medicine - Eden Avenue Cincinnati 19, Ohio Mr. D. V. Stroop, American Petroleum Institute, 50 West 50th Street, New York City 20. Dear Mr. Stroop: Attached is our report on the technological, biological and chemical aspects of the carcinogenicity project. If possible, will you please have this progress report duplicated for distribution to each of the members and associates of the API Medical Advisory Committee prior to the meeting in Chicago on April 23? I should appreciate if you could let me have five copies for distribution to the various people here at the Kettering Laboratory. At least twenty additional copies should be brought to the committee meeting on April 23 for those members who will not have theirs before them. We should like to submit for publication in the journal "Cancer Research" the data in Table II of the report with the dose-response curves of the two strains of mice to the various concentrations of methylcholanthrene. Will you please advise the members of the Medical Advisory Committee of our intentions in accordance with the machinery set up for publications at the recent meeting at the Kettering Laboratory? We shall conform to the suggested 30-day waiting period before submitting our paper to the editor of the Journal. The fact has already been published in this journal that high-boiling catalytically cracked oils have a marked carcinogenic potency toward mice, (see, for example, Sugiura, Smith and Sunderland, "Cancer Research" vol. 9, p. 631, 19^9). Hence we consider it highly desirable to Include in our paper the TI curves for Oils No. 8 and No. 9 in order to demonstrate that while it is true that some highboiling catalytically cracked oils have a high potency, an equal number will be found to have a relatively lo$* position on the scale. For the time being, these oils will be designated simply as typical oils of this type. Very truly yours, AWH ef /s/ A. W. Horton A. Wesley Horton Enc . C.C. : Dr. Mclver Woody Dr. Kieffer Davis API 04949 *9 C0FY COPY C0FY For Information Only - Not for Publication Report to Subcommittee on Carcinogenicity of the API Medical Advisory Committee PROJECT ON CARCINOGENICITY AT THE UNIVERSITY OF CINCINNATI A tentative list of samples to be studied during the period, July 1950 to July 1951, was attached to the progress report which was distributed prior to the recent interim meeting on March 25, 1950. The collection of these refinery products is well under way, and programs have been set up at the various laboratories of the companies concerned to carry out the distillations and spectral analyses desired. A fair proportion of this work has already been completed and the spectra received seem very satis factory for the prediction of the carcinogenic potencies of the oils. As rapidly as the facilities and the availability of animals permit, samples selected on the basis of the process and analytical data are being forwarded to Cincinnati for testing. At the same time we are making it a practice to advise each company of the interpretation of the spectral data submitted in order that they might know as early as possible the processes and products in their refineries which represent the greatest potential hazards from the cancer standpoint. The biological experiments employing refinery samples, and fractions derived therefrom in the laboratory, are listed in the attached Table I. The potency Pmc is defined as that concentration (in grams/100 ml.) of methylcholanthrene in benzene which has the same carcinogenic action on the mice as the oil In question. The values of Pmc for those oils on which the tests are essentially complete are presented in Table I. The concentration standards employing solutions of methyl cholanthrene and 9,10-dimethyl-1,2-benzanthracene are listed in Table II. It will be recalled that the tumor index, TI, has been defined by the following relation: TI = Number of mice which have developed tumors "Effective group" "Effective Group" = Number of mice given adequate exposure * Original number of mice employed - Number of mice which have died without tumors prior to the appearance of tumor in the "average tumor-bearing mouse" The "average mouse" Is designated as the median in a simple arithmetic array of the times of appearance of tumors. API 04950 % 2 It will be noted from the times required to reach tomor indices cf 5^ that the albino CFW mice are much more susceptible to the carcinogenic action of methylcholanthrene than are the brown C3H mice when treated with the lower concentrations. Thus the CFW strain -eves a very useful tool to determine the relative carcinogenicities . low potency oils in the shortest time. However, it has been ouna that the concentrations of methylcholanthrene greater than 0.15 gm./lOO ml. give very ambiguous results with this strain. These undesirable side effects are not as disturbing in the brown C3H mice, and hence this strain is used for the higher potency oils almost exclusively. The preliminary results with 9,10-dimethyl-l,2-benzanthracene (DMBA) indicate that it may be an equally satisfactory carcinogenic standard. Experiments 211 through 213 employing the nonvolatile solvent, dodecylbenzene, have run into serious difficulties because of a severe crusting effect of the skin of the mice caused by the solvent. Sample 218 is being tested to determine the effect of the viscosity of the solvent on the response to methylcholanthrene application. In Table III are listed the painting and washing experiments being run at the present time. More severe tests are planned em ploying a frequency of application of three times per week. The following four samples have been selected for exchange ex periments to be run concurrently by the group at New York University: Oils Nos. 8, 8-4, 25, and 25-1. A standard solution of 0.1 grams/100 ml. of methylcholanthrene in benzene will be included for further correlation. We have discussed the desirability of communicating with representatives of the Institute of Petroleum to arrange a three-way exchange program em ploying these same oils. To date in the chemical laboratory the presence of the following polycyclics in high-boiling catalytically cracked oil has been de termined with a good degree of certainty: perylene, 4-methylpyrene and chrysene. From preliminary data on the distillation fractions it would appear that the pyrene and the perylene nuclei predominate among the poly cyclic aromatic hydrocarbons in these oil3 boiling from 750 to 1100F. A continued effort is being made to isolate the compound responsible for the absorption peak at 430 millimicrons. This ma terial has an extremely high boiling point, and it seems not unlikely that isolation and characterization will prove it to be one of the highly carcinogenic dibenzpyrenes. AWH ef April 7, 1950 A. Wesley Horton API 04951 \ Table I % Skin Painting Experiments on High Boiling Samples -- - API Sample jlumber Process 5 Straight Bun Distilla tion 6 Thermal Cracking 6-1* Dilution 7 TCC 8 FCC 8-1* 8-2* 3-phase Deasphalt ing With Mixed Hexanes Same as 8-1 8-3 Filtration Dewaxing of No. 8 8-4 Dilution 9 TCC i Product Gravity Boiling Range 0F 10* 90* E.P.. * - F. Sulfur * p MC Residuum From Wilmington Crude 11885 Tar V-3631 77* Oil No. 6 23* Benzene Bottoms N8295-2 Decanted Oil W-3632 Oil re covered From Upper Liquid Phase Oil re covered From Lower Liquid Phase Press Oil (85* of Original) 50* Oil No. 8 __v(White Oil 5U**(W. Texas Resid. Syn. Tower Bottoms 12.8 5-2 20.2 11.1 11.3 18.4 59-940 586 58-666 463 570 550 760 ; 488 608 98-756 1.97 0 1.55 jco.03 0.39 CO. 01 1.01 0.6 0.3 0.15 0.94 0.43 0.02 1 API 04952 T Table I Page 2 --------- 1 | API jsaaple dumber Process i 1 10 l i 11 TCC Houdry 12 FCC Product Fuel Oil Syn.Tover Bottoms Decanted Oil Gravity Boiling Range 0 F. 10# 90# E.P. # - F. Sulfur PMC 11.6 4.3 630 757 548 81-700 0-53 0.4l 0.11 18.1 450 912 0.54 O.65 12-1* Pentane Deasphalt ing Asphalt in benzene (2.3 g-/ 100 ml. 12-2* Chromato graphy 1 (Silica gel) Non-Aromatics (Cut with 20# Heptane) 12-3* Pentane Deasphalt ing 2nd Asphalt in benzene (2. g./lOO ml. 12-4* Distilla tion (1-plate vac.) Aromatics Boiling 510710 F. (Corr.) 12-5* Same as 12-4 Fraction boiling 10101065(6 g./ 100 ml. benzene) 12-6* Same as 12-4 Residue boil ing > 1065 (5 g./lOO ml. benzene) 13 Polyforming Tar 14 Solvent Extract Extraction from Kansas (Furfural) 200 stock 9-7 10.3 75-740 762 869 98-920 1.43 -- 15 Same as 14 Extract from Okla. 4oO pale 10.9 853 960 0.81 API 04953 Table I ,__ _____ API Sample Dumber Process Product Gravity Boiling Aenge 6 ]r 100 900 E.P. 0 - F. Page 3 1 Sulfur PMC l6 Solvent Extraction (Phenol) 17 Solvent Extraction (Duosol) IB 19 20 20-1* Viscosity Breaking Naphtha Reforming Thermal Cracking (150 Cat. G.O. in Feed) Dilution 21 Desulfurization of No. 8-3 by catalytic hydrogena tion 22 Cyclover sion 23 FCC 24 Thermal Cracking of No. 23 25 FCC 25-1 Dilution Extract from Coastal 900-X Extract from Calif. waxy residuum Cracked Residuum Tar Tar 500 Oil No. 20 500 Dodecylbenzene Hydrogenated Heavy gas oil Heavy gas oil Heavy cycle gas oil Tar 700 + Bottoms from Heavy Cycle Gas Oil 500 oil No. 25 (White (Oil 500 (W. Texas (Resid. 11.0 7-0 50-915 - - 50-950 0.9 -- 6.0 17.0 420 706 4.7 83-930 0.85 -- 0.46 -- o.ie 18.1 595 870 0.15 -- 24.0 26.1 572 686 98-722 611 769 98-828 0.2 0.71 13-5 564 930 98-1050 1.26 -* * Sample prepared in laboratory. API 04954 * Table II CONCENTRATION STANDARDS WITH METHYLCHOLANTEENE (MC) AND 9, 10 - DIMETHYL - 1, 2 - BENZANTHRACENE ^DMB/.) API Sanple Nunber Carcinogen Solvent Frequency Concentration of (g./lOO ml.) Application Tine After 1st Fainting Required to Reach 50$ T.I. C3H CFW 201 202 203 20b 205 206 207 209 210 211 212 213 218 2l4 215 216 217 MC MC MC MC MC MC MC MC MC MC MC MC MC DMBA DMBA DMBA DMBA Benzene Benzene Benzene Eenzene Benzene Benzene Benzene Benzene Benzene Dodecylbenzene Dodecylbenzene Dodecylbenz ene API-5 Benzene Benzene Benzene Benzene 0.010 0.038 0.075 0.15 0.30 0.60 1.00 0.45 0.02 0.10 0.30 0.04 0.30 0.30 0.10 0.05 0.01 3X/week 3X/veek 3X/veek 3X/veek 3X/week 3X/veek 3X/veek 3X/veek 3X/veek 3X/veek 3X/veek 3X/veek 3X/veek 3X/week 3X/veek 3X/week 3X/week -- -- 2l6 days 140 days l8l days 116 days 108 days 78 days 77 days 84 days 39 days 87 days 6b days 67 days -- -- -- -- -- -- 48 days -- -- -- -> -- -- -- API 04955 Table III Skin Painting and Washing Experiments (CFW Mice) API Semple Humber Oil Applied Frequency of Application Period of Exposure to Oil Before Re moval By Washing With Soap and Water Time After 1st Painting Required to Reach 50$ T. I. t-OOo 8 8 lX/week Control (no washing) 112 days 8 IX/week 10 min. No tumors in 219 days 301 8 lX/veek 1 hr. No tumors in 219 days 302 8 lX/veek k hrs. No tumors in 219 days API 04956 For Information Only ,1 Not for Publication AMERICAN PETROLEUM INSTITUTE SUBCOMMITTEE ON CARCINOGENICITY Minutes of Meeting April 23, 1950 Hotel Sherman Chicago, Illinois Members Present Associates Present Mclver Woody (Chairman) Marshall Clinton T. M. Frank A. E. Hoag J. P. Holt (Rep. by R. E. Eckardt) T. J. Kelly J. W. Long M. N. Newquist Chas. A. Swan L. 0. Crockett Allan E. Dooley R. W. Faulk R. M. Landon H. P. Lankelroa K. G. Mackenzie (Rep. by H. R. Warrick) R. M. Shepardson Members and Associates of Medical Advisory Committee W. 0. Armstrong V. C. Baird F. F. Boys Kieffer Davis E. K. Linder E. P. Luongo B. B. Reeve E. R. Ware E. W. Adams R. D. Bent R. C. Cole T. E. DeVilliers L. M. Henderson C. A. Neilson F. M. Watkins Guests N. W. Bolyard - Standard Oil Co. (ind) Philip Drinker - Harvard School of Public Health J. W. Hammond - Humble Oil and Refining Co. Howard Hansen - Esso Standard Oil Co. A. W. Horton - University of Cincinnati W. C. Hueper - National Cancer Institute, Bethesda. Md. R. A. Kehoe - University of Cincinnati R. C. Page - Standard Oil Co. (N. J.) tT. J. Phair - University of Cincinnati H. G. S. van Raalte - Shell Oil Co., Curacao, N.. Ant. W. E. Smith - New York University D. V. Stroop - American Petroleum Institute P. M. Waddill - Phillips Petroleum Co. Total in attendance - 44 $ 2 Members Absent L. E. Curtis W. R. Levis Associates Absent L. C. Beard, Jr. H. G. M. Fischer The minutes of the November 10, 1949 meeting were approved. Dr. A. W. Horton presented a progress report, copies of which had been sent to all members and associates on April 11. This report was supplemented by a series of lantern slides showing poten cies of some of the oils which have been tested. With respect to the analytical phases. Dr. Horton stated that many compounds had been isolated but very few had been identified as yet. Perylene, 4-methyl pyrene and chrysene have been definitely identified as constituents of high-boiling catalytlcally cracked oils. Dr. Horton described the data which was to be submitted for publication in "Cancer Research". *The potency curves of oils 8 and 9 (see Table I of Dr. Horton's report) would be included as being typi cal examples of the oils being studied. In the discussion which followed, many of the members and associates voiced a request that a complete and detailed report be prepared by Dr. Horton. It was pointed outthat such a report would be of particular benefit to new members andassociates. Dr. Horton's report was accepted and approved. Mr. R. M. Shepardson described the work of his company on the development of a quick laboratory test for measuring the potential carcinogenicity of petroleum products. As a numerical expression of potential carcinogenicity, the number of days required for 50 per cent of the mice to develop tumors after discarding all mice which had died API 04958 -3- 1 without tumors, has been tentatively chosen. Of 64 samples tested to date, a satisfactory correlation has been found between the biological tests and the ultra-violet absorption measured at 360 mu on the por tion of the sample separated by distillation and boiling between 630 and 950 F., when correcting for difference in viscosity, mid-boiling point and concentration of the 650-950 F. material. This study is being continued on a larger number of samples. The subcommittee expressed its thanks to Mr. Shepardson for his presentation. Dr. R. E. Eckardt reported on some of the work* being done at Memorial Hospital. Cancers have been produced in two monkeys out of six who had been painted with a high-boiling oil twice a week for about five years. This is the first time that skin cancers have been produced experimentally in monkeys. Dr. Eckardt reporting on washing experiments said that re sults to date indicate that washing offers some protection but not absolute protection. With groups of 30 mice, application of the oil and washing after five minutes resulted in a reduction in the number of tumors and no cancers after one year. Washing the mice one hour after application produced tumors in four mice and cancer in one mouse of the group of thirty. Washing the mice six hours after appli cation resulted in the development of cancer in three mice. In a group of sixty mice which were painted with only one application of a high-boiling oil, tumors were produced in two mice * See attached copy of paper "Experimental Analysis of the Carcino genic Activity of Certain Petroleum Products" for additional informa tion on this work. API 04959 / -4- ? and cancers In two additional mice. The first tumor appeared after 92 days and the first cancer after 274 days. No tumors or cancers appeared in a control group on 100 mice. This subcommittee expressed its thanks to Dr. Eckardt for his presentation. Dr. J. J. Phalr presented a progress report on the epidemio logical study which he plans to get under way about July 1, 1950. pr. Phalr distributed mimeographed copies of his report. During the discussion it was brought out that, to date, there have been no cases of skin cancer in which the employe has claimed that exposure to these high-boiling oils was the cause. Dr. Phair's report was accepted and approved with the under standing that the word "approved" would be changed to "needed" where it fits the context of the report. Dr. H. fi. S. van Raalte told about a fishing village on the island of St. Martin where the inhabitants, all of Danish ancestry, can trace their ancestry back about 200 years on the island. He stated that most of the men develop skin cancers by the time they reach age 40. Most work at fishing and handle tarred nets and tackle. A few who have worked in the refinery or at Aruba apparently have not had skin cancers. Dr. W. C. Hueper' (National Cancer Institute) said that he had talked to a nurse in an asphalt shingle plant in the western part of the United States and that the nurse had reported cases of cancer on the dorsum of the hands. Dr. Hueper said that a petroleum asphalt API 04960 / -5- } was being used and that it would be well to keep an eye on this ma terial with respect to both producers and consumers. The subcommittee recommended to the Medical Advisory Com mittee that it should approve: 1. Publication of the report as described by Dr. Horton in his letter of April 7, 1950 to D. V. Stroop. 2. The proposed epidemiological study as described by Dr. Phair. Mclver Woody, M.D. Chairman Allan E. Dooley Secretary API 04961 For Information Only - Not for Publication EXPERIMENTAL ANALYSIS OF THE CARCINOGENIC ' ACTIVITY OF CERTAIN PETROLEUM PRODUCTS* William E. Smith, M.D., Douglas A. Sunderland, M.D., and Kanematsu Sugiura, D.Sc. from the Institute of Industrial Medicine, New York University-Bellevue Medical Center, and the SloanKettering Institute for Cancer Research, New York, U.S.A. As part of the preventive medical program of a petroleum company, we conducted tests for carcinogenic activity on approximately 400 samples from refinery, laboratory and wax works operations. Each sample was tested by painting on a group of 30 mice. Oils from Catalytic Cracking Process: Carcinogenic activity was found only in fractions distilling above 700 F. The carcinogeni city of the most potent oils studied was markedly reduced by dilution to approximately 10# concentration with non-carcinogenic oils. Blends containing not more than 10# of potent oils elicited only a few tumors and these were benign. Waxes: Unrefined petroleum waxes elicited cancers late and infrequently, but their aromatic extracts were very active. The hazard in wax works thus appears to be associated with the aromatic compounds in unpurified wax and not with the paraffins. * These studies were carried out under a grant from the Standard Oil Co. (N.J.) and certain affiliates in cooperation with the Medical Department of that company. All samples were prepared and supplied by the Standard Oil Development Company. API 04962 '* For Information Only - Not for Publication REVISED DRAFT EXPERIMENTAL ANALYSIS OF THE CARCINOGENIC ACTIVITY OF CERTAIN PETROLEUM PRODUCTS. William E. Smith, M. D., Douglas A. Sunderland, M. D. and Kanematsu Sugiura, D.Sc. from the Institute of Industrial Medicine, New York University-Bellevue Medical Center, and the Sloan- I Ketterlng Institute for Cancer Research, New York, U. S. A. Occupational tumor problems have been much less commonly observed in the petroleum industry than in the Scottish shale oil trade. Occasional tumors have, however, been described, and some petroleum oils have been shown to elicit tumors in experimental animals. For these reasons, the Standard Oil Company (New Jersey) and certain affiliated companies began a general Investigation into the question of possible occu pational tumor hazards for workers in refineries. In colla boration with this study, we have carried out tests for car 1 cinogenicity on approximately 400 samples of oils and waxes derived from various phases of plant and laboratory processes. The samples were prepared by the Standard Oil Development Company. The first group of materials studied were from an ex perimental catalytic cracking operation. In this process, developed extensively during the past ten years, oils are cracked at a relatively high temperature in contact with a catalyst generally composed of mixtures of silica and alumina. From the classic experiments of Kennaway, Cook, Twort and others, it was known that petroleum, like coal and other API 04963 t# -2- bituminous materials, may acquire carcinogenic properties as a result of reactions brought about by extensive thermal decomposition. Our first tests were conducted with samples of high boil (slide) (slide) #2 (slide) #3 X (slide) ing, catalytically cracked oils. These proved highly potent in bringing about cancer when painted on the skins of mice. They also elicited papillomas and occasional cancers from the skins of rabbits, and, after years of painting, from the skins of monkeys. Preliminary tests showed that white mice obtained from a commercial breeder (Rockland Farms) gave tumors somewhat more quickly than dark-skinned C57 mice, and we have routinely used white male mice from this breeder. It was found that for practical purposes essentially comparable information could be gained from mice tested in a group of 30 as compared with a group of 100 animals. We have therefore tested each sample on a group of 30 mice. If groups much smaller than this are used, difficulties may arise from loss of animals in the course of the necessarily long-term experiments. The mice are painted with the test material three times a week throughout their lives, unless the experiment is dis continued earlier. Very potent samples have elicited papil lomas as early as 29 days and cancer after 70 days; but for moderately potent materials a period of 250 days is usually necessary to gain an impression of their activity, and many samples must be painted much longer before tumors appear. API 04964 04 - 3- (slide) Statistical methods proposed by the Standard Oil De #5 velopment Company have been adopted which permit the data from each sample to be charted graphically in a manner that permits one to see at a glance the non-tumor mortality, the number of animals developing benign papillomas, the number developing cancers, and the rate at which the tumors appear. This slide shows such a graph, on which is given data ob tained from mice painted with an acetone solution containing 0.2% of the pure carcinogen, methylcholanthrene. The days at which the animals were observed are indicated along the bottom. The percentage of survivors with or without tumors at any given time can be read off the scale at the right. The percentage of animals dying with or without tumors can be read off the scale at the left. The shaded area indicates the time of appearance of the first cancer and the number of cancers that developed. The percentage of animals dying without tumors can be read by reference to the lowest line on the chart. It may be guide to toxicity of the sample but often connotes deaths from fighting or intercurrent infection. (slide) The next slide gives the results of painting a sample of #6 high boiling catalytically cracked oil. It shows a carcino- . genic activity not greatly less than that of the 0.3% solution of methylcholanthrene just shown. A mixed colony consisting of 13 male and 12 female mice was used in this experiment. The data for each sample under test is entered from month to (slide) #7 month on cnaphs such as these. 0# -4- For convenience in comparing the carcinogenicity of i large numbers of samples, two indices have been employed. i The Tumor Index is the percentage of animals, surviving 90 ! days or longer, that develop either papillomas or cancers. The Cancer Index is the percentage of animals, surviving 90 i days or longer, that develop cancers. The activity of each sample can then be rated by a simple numerical fraction, the Cancer Index over the Tumor Index. V* (slide) The next slide, divided into two groups, shows results | #8 t at 250 days on 10 samples of catalytlcally cracked oils re ceived from refinery operations. The first group, consisting of five samples, contained relatively little high boiling material (less than 30# distilling above 700 F.). It is seen that they were practically devoid of carcinogenic activity. Only two of the five induced any cancers and then in only a small percentage of animals. It is of interest to i- note that the most active sample in this group (207) con tained the greatest percentage of high-boiling material (28#). By contrast, the second group of five samples gives the re sults on catalytlcally cracked oils that contained large amounts of high-boiling materials (over 45# distilled above 700 F.). It is seen that all of these possessed a very high carcinogenic potency. (slide) The carcinogenicity of such high-boiling oils can be #9 effectively reduced by dilution with non-carcinogenic oils. Here is a set of tests on blends containing varying propor tions of high-boiling material. No reduction in potency was API 04966 4 -5 ~ found when the blend contained 67# of the active oil. When only 55% was present, the carcinogenicity fell off; and when the amount was reduced to 29%, no cancers whatsoever resulted at 250 days, though a considerable percentage of animals still yielded benign papillomas. Further experiments with dilutions of another oil of this type have shown comparable results and are also shown in Slide #9. In these experiments it is indicated that when the concentration of the active oil was reduced by dilution to somewhere between 10 and 20# (8 .and 16# boiling above 700 F.), the carcinogenicity of the oil is abolished in that no cancers are produced. The carcinogenicity of these oil samples has thus been shown to be associated with the high boiling material. The (slide) problem has been further narrowed down by demonstrating that #10 the carcinogenic activity resides in the aromatic fraction of the oils. Here are tests on fractions of a high boiling oil i subjected to chromatographic separation on silica gel. It is seen that the paraffinic components were devoid of carcino genicity whereas the cumene eluate, which contained the aromatics, was extremely potent. This finding has been applied in the study of materials from wax-works. In the manufacture of waxes, certain oils are cooled and the solid material, or wax, which separates out is collected in a press. Samples of these crude waxes were melted at 60 and planted on mice. After 250 days, very few animals thus painted showed any tumors. When the paintir^, was kept up for 450 days, however, tumors were Induced by all AT?I 04967 9t -6- of 8 samples of crude waxes but the percentage of animals that developed tumors was small. Often, merely papillomas and no cancers resulted. By contrast, the aromatics ex tracted by silica gel from these crude waxes possessed very I marked carcinogenic potency. In every instance, they elici- j ted considerably mere tumors than the whole crude wax from which they were obtained. Furthermore, the aromatic frac- 1 tions regularly produced one or more malignant tumors. It therefore appears that the carcinogenic hazard in the case of crude waxes is due to the presence in them of aromatic components, and not to the paraffins which compose the final purified waxes. .i 1 V i API 04968 T "! f* LIST OF SLIDES 1. Cancer and papilloma as seen on a mouse painted with a sample of high boiling catalytically cracked oil (color photo). 2. Histological section of tumor shown in Slide 1. 3. Papillomas on ear of rabbit painted with same material applied to mouse shown in Slide 1. 4. Ditto (monkey) 5. Graph showing data from painting methylcholanthrene (Exp. 22) 6. Graph showing data from painting a sample of high boiling catalytically cracked ail (Sample III, Exp. 11) N.B. We have removed the cross-hatching which this graph erroneously shows between 40 and 70 days. 7. Definition of Cancer and of Tumor Indices. 8. Cancer Index/Tumor Index data on oils with various boiling ranges. 9. Reduction of carcinogenicity of high boiling oils by dilution with non-carcinogenic oils. 10. Carcinogenicity of aromatic contrasted to paraffinic fractions of a high boiling catalytically cracked oil. u. Carcinogenicity of crude waxes contrasted to that of their 11 aromatic fractions. API 04969 0* TUMOR INDEX: CANCER INDEX: SLIDE #7 TOTAL NUMBER OF ANIMALS THAT DEVELOPED TUMORS ORIGINAL NUMBER OF ANIMALS LESS THE NUMBER DEAD AT 90 DAYS WITHOUT TUMORS TOTAL NUMBER OF ANIMALS THAT DEVELOPED CANCER ORIGINAL NUMBER OF ANIMALS LESS THE NUMBER DEAD AT 90 DAY WITHOUT CANCERS API 04970 f SLIDE #8 SAMPLE % DISTILLING CI/TI SAMPLE % DISTILLING CI/TI NO. ABOVE 700P. at 250 days NO. ABOVE 700P. at 250 217 less than 1 213 3 224 10 207 28 219 3 0/0 0/0 0/0 4/12 4/4 206 74 173 78 223 78 216 45 212 78 33/67 38/57 38/77 46/71 67/87 API 04971 r$ SLIDE # 9 REDUCTION OF CARCINOGENICITY OF A HIGH BOILING OIL BY DILUTION WITH NON-CARCINOGENIC OILS MH 101 (4555 distilling above 700F) BLEND CONTAINING: 127 67# MH 101 121 55% MH 101 115 29% MH 101 173 (7B% Distilling above JOOF) 175 Non-carcinogenic oil 176 10 173 177 2056 173 178 3056 173 179 40g 173 CI/TI at 250 days 27/62 23/67 13/57 0/27 CI/TI at 281 days 36/50 0/0 0/4 16/36 3/24 44/59 API 04972 ru.- SLIDE # 10 192 193 1 Silica Gel 196 197 CANCER INDEX TUMOR INDEX at 250 days API 04973 CRUDE WAX 8/19 7/7 4/4 0/7 0/4 0/4 4/4 4/4 r> SLIDE #11 CANCER INDEX TUMOR INDEX at 450 days AROMATIC EXTRACT 24/38 23/35 17/43 14/34 9/13 8/30 4/30 Vl9 API 04974  UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH CARLE ADDRESS: EETLAt. CINCINNATI TELEPHONE: CAPITOL MU ' Mr. D. V. troop, The American Petroleum Institute = " 'Joe-h K.O-J-Vi ct,,ee* f Dear Mr. troop! I am sending you herevith, for your information, a statement of expenditures made on behalf of The American Petroleum. Institute for the first quarter of 1950* If you have any questions or comments, Doctor Eehoe would appreciate your bringing them to his attention. Very truly yours r.nc. API 04975 o UNIVERSITY OF CINCINNATI KETTERING LABORATORY ACCOUNT OF AMERICAN PETROLEUM .INSTITUTE For the First Quarter of 1950 .aTES (Based on Proportion of Time Actually Spent ion Project) Francis Heyroth Supervision John Phair - Wesley Horton - Chemical Assistance prank Dutra - Pathological Assistance Frank Cleveland - R R Russell Tye Ruth Pierle Sylvan Witherup - Chemical Assistance -r n It ft Harold Schlecht Dorothy Templeton - Technical R Assistance H Karl Eorpi - ft ft 75.00 1375.02 1950.00 50.00 187.14 900.00 1125.00 11.51 8.05 330.05 153.50 6145.27 tCELLANEOUS EXPENSE purchase of Animals............................................................................. '458.88 Laboratory Supplies * .................................................................. . . Traveling Expense.................................................................................... proportion of Secretarial, Library, Janitors, Wash Boys, Draftsman, Shipping Clerks, Animal Caretakers, Histopathological Preparation etc .... ................................. Proportion of Heat, Gas, Electricity, Steam, Telephone, Maintenance, Pensions, Annuities etc ........ TOTAL ............................................... 11,997.35 Balance Available for Work' in 1950 at End of 4th Quarter 1949 ....................................................$34,594.15 Receipts - January 12, 1950 ........................................................ Expenditures - 1st Quarter 1950 ............................................... 38,963.39 73,557.54 v 11,997.35 ^ Balance Available for Work in 1950 at End of 1st Quarter 195 . ............................................... $61,560.19 s API 04976 May 16, 1950 Dr. Robert A. Kehoe University of Cincinnati Dept, of Preventive Medicine and Industrial Health Cincinnati, Ohio Dear Dr. Kehoe: Your letter of May 9 has been received Just as I am pushing off for a week; of meetings in Atlantic City and Chicago. Gome time between meetings I shall study your memorandum. Upon my return I shall give you my suggestions. Yours very truly, DVS:prd D. V. Stroop Executive Assistant API 04977 g KETTERING LABORATORY ,lL(GE OF MEDICINE--EDEN AVENUE ^elNNATI It. OHIO o UNIVERSITY OF CINCINNATI a DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH May 9, 1950 CABLE ADORERS: EETLA1, CINCINNATI TELEPHONE: CAMTBL MM v 5 f i Mr. David Stroop. Director of Safety, American Petroleum Institute, 5_' Vest pcth Street, New York City 20. Dear Mr. Stroop: I am sending you herewith several copies of a memcrandun I have prepared for submission to the sponsors of the experimental vcrk cf the Laboratory. I believe this will be self-explanatory, but I have considered it desirable to append a note to It, In explana tion cf its length, which seems a bit long. It Is my firm conviction that there is nothing which this Laboratory can do for industry, and specifically for the petroleum industry, which would be more useful in the long run than to spend some of our efforts in training medical men to appreciate the general problems of industrial health. This is a service that industry needs, and I am sure that it can afford to pay a nominal cost for the benefits to be achieved. Therefore, I have gone to some length to explain our program and our ideas in connection with It. I realize that this may be a very poor time to suggest more exten sive expenditures. On the other hand, I think this should be presented for consideration. It might have been wise to do it at the formal meeting of the Medical Advisory Committee, but, quite frankly,I did not want to cloud the issue*under consideration by bringing forward a proposal of this type. I leave entirely to your discretion the manner and the time of presenting this. In my feeling, if it were approved in principle, we would be in position to handle the situation fairly well this year, since our cost for the current year will probably be relatively small. I shall appre ciate hearing from you at your convenience concerning this matter. Sincerely yours. F.AK ef nc. Robert ~A~. lie"Hoe', 'M.' t)T a i *t i API 04978 i i The Institute Of Industrial Health of the University Of Cincinnati oU UNIVERSITY OF CINCINNATI THE GRADUATE SCHOOL OF ARTS AND SCIENCES INSTITUTE OF INDUSTRIAL HEALTH TERING LABORATORY OF APPLIED PHYSIOLOGY COLLEGE OF MEDICINE . EDEN AVENUE CINCINNATI IB. OHIO MEMORANDUM CABLE ADDRESS' KETLAB. CINCINNATI TELEPHONE UNIVERSITY 2665 TO FES?ONSIELE EXECUTIVES OF ALL INDUSTRIAL ORGANIZATIONS INVOLVED IN THE EXPERIMENTAL PFOGRAM OF THE KETTERING LABPLATOFY, COLLEGE OF MEDICINE, UNIVERSITY OF CINCINNATI The developments of recent years in the field of industrial health and, specifically, the evolution and grovth of the activities of this Laboratory in this field, have posed a number of problems that are of considerable importance to this Medical College and University and are, likewise, matters of concern to industry. It is necessary to formulate certain policies and plans m order to deal with these problems on some more or less oermanent basis, and it is the purpose of this memorandum to obtain an expression of opinion from representatives of industry relative to such plans. The work which led to the creation of the Kettering laboratory began in the Department of Physiology in the Medical College in 1925, when the study of a single toxicologic and lygienic problem was undertaken for, and at the expense of, one .ndustrial organization. While this work was expanding beyond the space and facilities available in the laboratories of the Medical Jolle-ge, additional industrial organizations became interested in >ur engaging in other investigations. There being no source of funds .n the University by which to provide facilities for such work, a ;roup of three industrial organizations provided funds to build and quip a laboratory, which was completed late in 19JO, and was namc-d he Kettering Laboratory, in honor of the distinguished Indusrialist, scientist and inventor, Charles Franklin- Kettering, whose API 04980 )J c work, with his associate Midgloy and others, had created the industrial commodity (antiknock material containing tetraethyl lead as the primary ingredient) out of which our first industrial 'inves tigation grew. The significance of the foregoing comments is that Ameri can industry, with particular reference to the chemical industry, was on the way to its present dominant position in international production and commerce, creating, as it developed, the special industrial hazards which it had no proper means of appreciating or controlling. Historically, the same thing had happened in Germany, and it was inevitable that medical attention should be brought to bear on these problems by some means. The facilities available in the United States were very scanty and wholly inadequate, and, bysheer accident, wc were drawn into this type of work at a compara tively early time. The Laboratory, therefore, has developed, with something of a lag, in response to the needs of the situation, and since no other means was available, these developments, in the University, were financed by industry exclusively. From its small beginning, the Laboratory has expanded its equipment and personnel to fit the work that it has been able to accept, and with the completion, equipping and staffing of a new wing in July of 1949, which more than doubled the available space, its physical facilities accommodate a staff of more than one hundred persons, and its annua,, budget comes to about $4u0,0G0.0J per year. This growth and development has not been merely quanti tative but qualitative as well, in that experience with the problems of industry has contributed to the shaping of policies, methods of procedure and functions. It became apparent at an early date that the experimental work had to be applied in the industrial environ- API 04981 \m.) 1 j ment, and that much of it would have to be done with the practical problems of industry clearly in mind. This resulted in frequent consultations with industrial people, in a variety of direct professional services to industry, and in the acquisition of direct familiarity with the industrial organizations, plants, and per sonnel involved. This experience demonstrated, among other things, that trained personnel for the work of industrial health were not available. Therefore, nothing was more clear than that a Univer sity medical center such as this had the duty of making provision for professional training. For the most part, the facilities required for such training were available in the Colleges of this University, but a great deal of planning and organizing was necessary to put them to work. By July of 19^7 plans had been crystallized for this purpose, the Institute of Industrial Health had been organized in the Graduate School of Arts and Sciences of the University, and two graduate pnysicians had been enrolled for a course of three years of study and training as candidates for the degree of Doctor of Industrial Medicine. While these developments were in progress in this University, somewhat similar activities began and progressed elsewhere, in response to the continually growing requirements of American industry in these respects. Other centers of research or professional training, or both, have been established or are being established and developed. This Laboratory, however, which is the administrative and academic center of the Institute of Industrial Health in the Graduate School, and which, recently, was consolidated with the Department of Preventive Medicine to become the Department, of Preventive Medicine and Industrial Health in the College of API 04982 Ju 4. Medicine, has the unique character of being a university enter prise created and financed wholly by industry to serve industry. It embodies the willingness on the- part of an important segment cf American industry to invest appreciable sums of money in the solution of industrial problems by an organization that is responsible to tin. public. The presumption, based on the growth of the Laboratory, is that this has been a good investment. Because of this presumption, and in keeping with the good will that has developed out of years of direct and frank relationships with industrial management, certain changes in fiscal and operating policies are proposed for consideration, which, if generally acceptable, will be incorporated in future formal agreements between the Laboratory and its sponsors . The educational program of the Laboratory has created some expense, and the means of dealing with this expense-is a problem which it seems necessary and desirable to present to the industrial organizations involved independently and jointly in the financial support of the experimental work. One point must be made clear in this regard. There arc no funds available tc us at present from public or private sources, other than those earmarked for the prosecution of experimental work agreed upon between the University and industrial organizations. Nor can the University of Cincinnati, which is a municipal institution, provide funds for the support of any part of the experimental cr educational program of this Laboratory, it being caught, as are most American universities, on the two vicious horns of the dilemma of diminishing private gifts of all kinds and returns on endowment funds, on the one hand, and the increasing cost of all API 04983 ; 5. of its activities, on the other* The result of this is the necessity of turning to industry for the entire support of the activities believed to be necessary. Since everyone vho vants money turns either to government or to industry for it, this has a familiar sound. There is a difference, however, we believe, in that the entire productive effort of this enterprise is designed to benefit industry, in an area of great industrial need and weakness. Moreover, present trends in industrial legislation and practice, with reference to health and welfare, employee relations, <1 and community comfort and health (with specific stress on stream and atmospheric pollution), arc such that the present lack of adequately trained personnel in the field of industrial health is a serious and growing threat to American industry. If cur experience of the past twenty years is to be trusted, the urgent need for competent industrial physicians will have to be met in the near future Moreover, industrial management is more aware of this, we believe, than is the medical profession, in general, including those responsible for the training of physicians, and therefore we can expect to obtain understanding and support from industrial management in this matter before it will be forthcoming elsewhere. With these matters in mind, wc have considered the cost of our educational program carefully , and have decided to propose to the sponsors of our work that wc be authorized to add to the cost of all experimental work an overhead charge of lu per cent for educational purposes. This figure has been arrived at on the basis of previous cost accounting and estimates which extend somewhat into the future. Appended hereto, is a bulletin in which the program of graduate education is outlined, together with a API 04984 ./ w schedule of fellowship stipends offered to graduate physicians who are accepted for training. (The stipends arc- offered a3 a means of reducing the economic hurdle for physicians who may wish to extend their training beyond the already prolonged period required, thereby encouraging able but impecunious applicants. It is also evident that some inducement must be offered to potential candi dates, in view of the almost overwhelming tendency of graduate physicians to enter into other fields of professional practice.; Our intention is to accept four students per year for training if II satisfactory applicants are available. Present facilities in the Laboratory, and in the University generally, will not justify our accepting a larger number at this time. This would mean that we would have eight fellows (in two classes) in the school per year, since the third year group would be in residencies in industrial establishments for which they will be compensated by the industry in which they are working. (Arrangements have been made to take care of a certain number of trained men in these residencies, and additional arrangements can be made as required.) Under these conditions, the cost of all of the fellowship stipends will not exceed $22,800.00 per year, and will usually be somewhat less than this 3um. Various plans are under way to obtain funds for this purpose from other academic and professional sources, and to the extent that these succeed, the funds obtained will be applied against this cost, but it seems necessary in lieu of such sources to secure the financial structure of this educational program through funds made available by the supporters of the general work of the Laboratory. The cost of the instruction of graduate students, as the vor>v of thr Facultv of the Institute of Industrial Health is API 04985 / 7- / presently organized, varies a little from year to year- Much of this cost applied automatically against the budget of the Labora tory for experimental purposes, in that the time spent in instruction by members of the staff of the Laboratory is paid for by salaries authorized for experimental work. (Other members of the Faculty, in other Departments of the University, receive no additional compensation for services rendered in the Graduate School.] However, the time so expended by members of our staff has been recorded and made a charge against the educational program for the past two years. It came to about $10,0u0.u0 in 1947-48 and to about $15,000.00 in 1948-49- Other items of expense included the oost of instruction given by non-university personnel, the traveling expense of visiting instructors (lecturers), the cost of miscellaneous supplies, stationery, printing, books and equipment, and a reasonable share of overhead expense for light, heat, janitor service and the like. The total expense, exclusive of fellowship stipends, was $20,00u.00 in round numbers in the academic year 1947-48, and $21,uOj.OO in 1948-49- This cost can be expected to increase to some extent as cost accounting of any and all expense attributable to such professional training is more rigidly scrutinized and recorded. Moreover, the furtherdevelopment of the professional curriculum will involve some additional cost, since not all of the Departments of the University arc staffed adequately for the purposes of consultation and instruction. To the extent that the Laboratory needs and can make adequate use of consultants in a number of fields in which demands arc made on us by industry, we shall undertake to augment the resources of these Departments. For example, consulting services and surveys in the field of Industrial Relations, with API 04986 / specific reference tc :cb appraisal and fitness, employee morale and production, and other aspects of the human equation in indus try, merit much more attention, study and research than they have had at the hands of professional people. The work of the Harvard School of Business Administration is a notable example of what can be done b, competent people in this field of study. On the whole, it is estimated that the cost of our program of graduate training^, including provision for fellowship funds not otherwise available, will rarely exceed ^bO,OOu.OJ in any one year, and that an overhead charge of not more than 10 per cent of our experimental budget U395^5^ in 1950) to this purpose, would secure the educational program indefinitely . Actually the cost i i be applied directly to the cost of any experimental project would not come to 10 per cent, but would be nearer to 5 per cent. It is not our intention to accumulate any special educational fund, but to distribute the cost of graduate instruction annually in such manner as to balance receipts and expenditures yearly. Finally, it is our belief that an Integrated program of medical and hygienic services to industry, of investigative work and of graduate instruction in the field of industrial health, is all of one piece; that these are related and complementary functions , and that the separation of the one from the other in terms of function or expense is disadvantageous and unrealistic. Therefore, we take pleasure in offering this combination of functions to industry, as a proper service of this Universi'y to industry and to the community, at the actual cost that is required by a Univeisity organization to supply such services. We invite the pres^r-1- sponsors of the work of the Laboratory to narticipatc in API 04987 9this program, and request a response to this proposal, with the intention, if there is general concurrence in the proposal, of modifying all agreements with subsequent sponsors, to include this expense. Signed: __ Hobert A. Kehoe, M. 1)., director The Kettering Laboratory and The Institute of Industrial Health March 15, 1950 API 04988 May 25, i?5C Dr. Bobart A. Behoe nnlTsraltj of Cincinnati Hie Setterlag laboratory Collage of Nedlclne Cincinnati 19, Ohio Dear Doctor Kehoe: The --nranrim trmtanl tted with your letter of Nay ?th baa been considered sort thoughtfully. He feel eo farorehly disposed that ee suggest the inclusion of com suitable wording In our letter of agreement for the eeedng year. ' If job agree. It will amble ua to subnlt a pacific jropoaitlon to the Nodical Advisory Ccmlttaa 1 mail lately for acceptance prior to July 1, 1950. Far jeer cmeideratian a rough draft of uhat I have in nlnd la enclosed far yoar consideration. If you concur in tbla approach, please let e know and I'll circularise coplea of the draft to neabere of the Medical Advisory Ccmdttee for acceptance cr ccaaent. Jmrj truly youra. DVS:d / Enclosure / cc: Dr. Heifer Woody / P.S. If there haa bean any change in your eetlaated figure for/the 1950-51 budget, please gire ne the total to be used in the letter of agreemat. DTE API 04989 SCOT OUR Boord of Jdroetcro UnnlV of Cl--la--tl t |w^0 Cl--1--fttl 19, Cblo ^^ / SB, 1990 .Hf lr if 9sis nwinlinti li amtoorltj to toxicity and --do of oetl-- of --to in patrola-- prod--to for too |wr --11m JO-- 30, 1991, ftooordlnf1 C'*3 5 to too tor-- of too id-- --tod job--ry 0, 19*, --d -- too 'H'k tool* of o --rf-- tod--t for oyarotlag axpa--aa ofd/flo.ooo ' vlto too ohtorotoadim tot ft portion, not to >--* 10 par --t, tooll to niwlrtli in wpport of too tolnroUj'i of crotoftto trfttoUc. ^^ Upon racaipt/df yoor opproml of of too projoot vlto toll conditio--1 toll pfty 1-- too 0-- of floC)> too too --expanded toXonooioo of 30, 1990, to to you -- In--jr 1,19931. Zt lo --dorctood toot ony tola--0 rmolirlng in too fond on JO-- 30, 1991 olll to rotor--& to too A--rle-- Patrol*-- Dutltotii and toot -- oxsom ovor too --oat of too to&gst lo to to otllftfttiod or opairt vitomt vrltton antoorl--tlan. Tory tmly join, AMEKXCA1 nZROUBX 1W1BIB irooitosT Aoooytoi and Appro--d unraggi or Xtaroftto ito loord of Uroetovo API 04990 ^ tv ^j American Petroleum Institute SO WEST BOTH STREET NEW YORK 20. N. Y. 9tMlMti , kl* trW 30, 6956*^1 u^a^Vw ^CVvv. --.."fcojcfr iT />Xs*X\ -(nL of tto rejKt vlto mo r5 tbr'i 1, 1950. /I**) It^ andorotoot toot a* la tto cm Am 30, 1996 U1 to rta4 to tto totltato, ad toot ao oapoooo orvor tto oapont of tto tout lo to to otiljotod or opont without orlttoa oatoorlaotloa. [ i ffi!!|jiAjl ln.*,lj!l'!i*5!",^ ,T *r ' ....... ' 11 jg !g "\ API 04991 r &9 American Petroleum Institute 90 WEST BOTH STREET NEW YORK 20. N. Y. To Members Medical Advisory Committee June 14, 1950 Subject: University of Cincinnati Kettering Laboratory Gentlemen: For your consideration ve enclose a copy of a letter dated May 9 and memorandum dated March 15 both from Dr. Robert A. Kehoe who outlines a need for increasing the University's overhead charges against research projects carried on at Kettering Laboratory. You vill note that his proposed program of graduate training is expected to increase the total overhead percentage by more than 5% but less than 10%. As recommended in November 1949, the carcinogenicity budget for 1950*51 is $92,000. With the additional overhead. Dr. Kehoe estimates the maximum total budget should be Increased to $100,000 to cover the next 12 months. We believe the unexpended balance of current funds at Kettering Laboratory on June 30, 1950 will be at least $8,000; There fore, our payment of nev money should not exceed the $92,000 which is now available and on deposit at the Institute. In view of these facts and with the possibility that you may favor acceptance of Dr. Kehoe's recommendation, we enclose a rough draft of a modified letter of agreement for your consideration. Your comments, either favorable or unfavorable, should be mailed to me at the earliest possible date because the agreement should be submitted to Dr. Kehoe not later than June 26. If no objections are received on or before that date we shall assume you have none to submit. Yours very truly. DVS:fn Enc. ). V. Stroop . API 04992 ast-gisr,-' J COPY COPY COPY UNIVERSITY OF CINCINNATI Department of Preventive Medicine and Industrial Health May 9, 1950 The Kettering Laboratory College of Medicine--Eden Avenue Cincinnati 19, Ohio Cable Address: Ketlab, Cincinnati Telephone: CApitol 1414 Mr. David Stroop, Director of Safety, American Petroleum Institute, 50 West 50th Street, New York City 20. Dear Mr. Stroop: I am sending you herewith several copies of a memorandum I have pre pared for submission to the sponsors of the experimental work of the Laboratory. I believe this will be self-explanatory, but I have con sidered it desirable to append a note to it, in explanation of its length, which seems a bit long. It is my firm conviction that there is nothing which this Laboratory can do for industry, and specifically for the petroleum industry, which would be more useful in the long run than to spend some of our efforts in training medical men to appreci ate the general problems of Industrial health. This is a service that industry needs, and I am sure that it can afford to pay a nominal cost for the benefits to be achieved. Therefore, I have gone to some length to explain our program and our ideas in connection with it. I realize that this may be a very poor time to suggest more extensive expenditures. On the other hand, I think this should be presented for consideration. It might have been wise to do it at the formal meeting of the Medical Advisory Committee, but, quite frankly, I did not want to cloud the issues under consideration by bringing forward a proposal of this type. I leave entirely to your discretion the manner and the time of presenting this. In my feeling, if it were approved in principle, we would be in position to handle the situation fairly well this year, since our cost for the current year will probably be relatively small. I shall appreciate hearing from you at your convenience concerning this matter. Sincerely yours. RAK ef Enc. /S/ Robert A. Kehoe Robert A. Kehoe, M. D. * API 04993 0,1 KETTERING LABORATORY ALLEGE OF MEDICINE--EDEN AVENUE 0HCINNATI ig, OHIO UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH July n, 195: CABLE ADDRESS KETLAB. CINCINNATI TELEPHONE: CAPITOL MIA Mr. D. ,T. Streep, The American Petroleum Institute, 53 Vest 50 th Street, Nev York City 20. Dear Mr. Stroop : I am sending you herevith, for your information, a statement of expenditures made on behalf of American Petroleum Institute for the second quarter of 1950. If you have any questions cr comments. Doctor I'.ehoe vould appreciate your bringing them to his attention. Very truly yours, E. RP.. Fortllapge, Secretary o Dr Kehce ^ API 05 006 UNIVERSITY OP CINCINNATI KETTERING LABORATORY ACCOUNT OP AMERICAN PETROLEUM INSTITUTE For the Second Quarter of 1950 IES (Based on Proportion of Time Actually Spent on Project) Robert A. Kehoe - Supervision prancis Heyroth - Toxicological Assistance John Phair - Wesley Horton - Chemical Assistance prank Dutra - Pathological Assistance prank Cleveland - If II Russell Tye Ruth Pierle - Technical Assistance - It 11 Sylvan Witherup - Harold Schlecht - v Dorothy Templeton - Sari Korpi - Charles Walker - Waldo Younker - Karl Erautle - II it ff n ti n It 11 If fl tt n 200.00 50.00 1575.02 1560.00 3.00 21.15 900.00 1125.00 - 52.32 387.67 240.12 151.00 356.35 61.54 [SCELLANEOUS EXPENSE purchase of Animals Laboratory Supplies Traveling Expense . . .............................................................................. A Proportion of Secretarial, Library, Janitors, Wash Boys, Draftsman, Shipping Clerks, Animal Caretakers, Histopathologlcal Preparation etc ...................................................... Proportion of Heat, Gas, Electricity, Steam, Telephone, Maintenance, pensions. Annuities, Educational Expense etc...................................................... 6463.17 366.80 6115.81 1666.47 3836.43 2176.63 TOTAL..................................................... 20,625.31 Balance Available for Work in 1950 at End of 1st Quarter of 195............................... $61,560.19 Expenditures 2nd Quarter 195........................................ 20,625,31 Balance Available for Work in 1950 at End of Second Quarter of I95O...........................$40,934.88 API 05007 MEMORANDUM November 10, 1949 SUBJECT: RECEIPTS, EXPENDITURES AND ALLOCATIONS -- API MEDICAL RESEARCH FUND Contributions Received 19^5 19^7 1948 1949 TOTAL $28,900.00 27,800.00 98,300.00 64,340.00 $219,3^0.00 Expenditures Made Prior to November 10, 1949 Harvard University Toxicological Reviews Cutting Oil Study $37,000.00 2,500.00 39,500.00 University of Cincinnati Carcinogenicity Fluorine Study 120,413.00 5,000.00 125,413.00 Miscellaneous Books for Committee Use TOTAL EXPENDITURES BALANCE ON DEPOSIT ______ 57.77 Payments Required to Continue Current Projects Unitl 6-30-50 164,970.77 54,369-23 Harvard University Toxicological Reviews (3-14-50 to 6-30-50) 3,000.00 University of Cincinnati Carcinogenicity 38,963-39 '! Fluorine Study (11-28-49 to 6-30-50) 1,500.00 40,463.39 TOTAL PAYMENTS TO 6-30-50 BALANCE AVAILABLE 7-1-50 43,463.39 10,905.84 Tentative Budget for Tear Ending 6-30-51 Harvard University Toxicological Reviews 10,000.00 University of Cincinnati Carcinogenicity Fluorine Study 92,000.00 2,500.00 TOTAL TENTATIVE BUDGET CONTRIBUTIONS NEEDED TO FINANCE TENTATIVE BUDGET 94,500-00 ^104,500.00 93 59^-15 NOTE: If 1949 contributors should give 150^ of the 1949 contributions the total for 1950 would amount to $96,510. API 05008 THE EETTERINC LABORATORY COLLEGE OF MEDICINE--EDEN AVENUE CINCINNATI I*. OHIO 1 UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH November 2, 1950 CABLE ADDRESS: EETLAB. CINCINNATI TELEPHONE: CAPITOL UI4 Mr. D V. Strocr: , American Petroleum Institute, 5j Vest 50th Street, fiev York City 2 .. Dear Mr. Scroop: In accordance viti: the request in your letter of October / to Doctor Ecrtcn and duly transmitted to me, I have written a summary report for the purpose suggested. It is somewhat ever words, but I feel that I have trimmed it to the bone. Fifty copies of this are being sent to you by parcel post, and are expected to arrive by the time the fifty copies of the report proper reaches you by Pailway Express . I shall take additional copies with me for distribution to members of the Medical Advisory Committee and their technical advisors at the time of the meeting. It may be that they will wish to incor porate this as an abstract, so to speak, in tie larger report. Best regards. Sincerely yours 1 1 ApI 05040 1i Summary Report of Progress In The Appraisal Of The Potential Carcinogenic Properties of American Petroleum Products Introduction The history of cancer of the skin among persons vhose vork has involved intimate and prolonged contact with aromatic coal tars and oil shale, derived mainly from British experience, together with the less familiar record of scrotal cancer in the United States and elsewhere among men long exposed to contact with waxy gas oils and slack wax, has provided a background which has justified and brought forth much productive investi gation and promoted an alertness, within the industry, to this occupational hazard. Out of such background came the recent recognition of the possibility and, later, the fact, that specific carcinogenic substances could be concentrated or actually produced in certain materials subjected to certain modern technologic operations. Vith this recognition came the responsibility to appraise the potential hazard to petroleum workers and consumers from this source, and to find means of obviating any actual risk that might be found to exist. This responsibility has been assumed by the petroleum industry, through the A.P.I. Medical Advisory Committee, and a compre hensive investigation has been instigated under their sponsor ship. The staff of the Kettering Laboratory has welcomed the request of the Medical Advisory Committee that it undertake such an investigation, and has taken a pardonable pride in this manifestation of confidence in the efforts of the Laboratory API 05041 in the field of industrial health. The work was undertaken in the assurance that the whole-hearted help of the industry would be forthcoming, and this assurance has been fully justified. Scope of Investigation The plan of the investigation was laid out along fourgeneral lines; (a) a complete survey of refinery processes and materials which might have carcinogenic characteristics, in order to facilitate the selection of appropriate samples for biological testing; (b) the development and application of biological methods for measuring and expressing the relative carcinogenic potencies of the samples selected; (c) the investigation of chemical means for Identifying and determining carcinogenic materials in the samples; and (d) an epidemiologi cal program for obtaining present and future information on the actual occurrence, if any, of occupational cancer in the petroleum industry, and on the factors which may influence the occurrence of such disease. By means of these four approaches one might hope to assemble the facts in such a manner as to portray the breadth and significance of the potential hazard, to simplify and give precision to methods for defining and localizing the hazard, to formulate the measures for its adequate control, to provide early and effective diagnosis and therapy for any disease that might develop out of past or existing conditions, and ultimately to prevent the occurrence of disease of this type. A 3- Initiation and Propress of Program of Investigation Early in 19^9 the survey of the technological back ground of the industry was initiated by the Laboratory, with the advice and assistance of many well informed persons within the industry. Since that time, the gathering and analytical study of samples has been facilitated by invaluable technical help from the industry, through which the biological testing has been greatly simplified and greatly reduced in cost over that originally anticipated. The methods developed and employed for the biological and chemical examination of the samples have yielded highly gratifying results, and steady progress is being made in the accumulation of necessary and apparently reliable data. It is of the greatest importance that the methods of procedure and the manner of expressing the biological results be coordinated with those of British investigators working in the same field of endeavor. By such means the volume of data will be expanded automatically and inexpensively, while the checks on methods and judgments which stem from such scientific collaboration should prove to be valuable. During 1950, the epidemiological aspects of the program have undergone cautious development. This highly important part of the program presents difficulties which derive in no small part from lack of uniformity in the methods and records of medical examinations in the various units of the industry. The composite difficulties affect the scope and type of the epidemiological work, as well as the ultimate reliability API 05043 4. of the data. The complexities of the problem are being resolved i as rapidly as possible and in a spirit of good viii and j cooperation. Some data arc available, and it is expected that l { an orderly flow of information will be forthcoming during 1951. The ultimate scope of the epidemiological work will be determined on the basis of what seems feasible and capable of providing useful information. The Future of the Investigation I The investigation as planned and developed is on the way to achieving the intended purposes. The program should be maintained substantially in its present form, with such modifi cation or extension as may be indicated by subsequent experience The cost of the further prosecution of the work along current lines can be estimated with reasonable precision, the only important variable being the scope of the epidemiological work. The cost of the latter will depend upon the time and personnel which can be employed profitably in gathering and studying epidemiological data, and in maintaining such contact with the medical personnel of the industry as may be required to yield satisfactory information. The next budget, effective as of July, 1951, will hardly be less than $85,000.00 or more than $100,000.00. This total sum is arrived at without taking account of work of this type which may be accepted under the financial sponsorship of Individual units of the 'petroleum industry. The extent of such work, which would reduce the expenditures made on behalf of tho American Petroleum Institute, i API 05044 cannot be estimated at this time. From the Kettering Laboratory in the Department of Preventive Medicine and Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. By: v__ ""i / Robert A. Kehoe , M. t). director October 31, 195U \ API 05045