Document NE9BGJqxNBQ1vjendOOgzbagV

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1952 Sept-Dec DOC#: API029 DOCUMENT DESCRIPTION: Letters, Memos, Reports, Financial Reports & Other Relevant Documents from Sept-Dec, 1952 A U MAIL OV. T. X. R te k F n Annata Xtflalag coryontloa f t * City, T n s 3 199 z a i w w lning two l i n k m i n t f t r i n to a n 1 is tia s n tfca w ln ta t f tfea M a s * n a j n * i i r l w i j c a n lttn anting n M y 10, 199. Z ftl not n a in m an te* tallo * art um inllj it fen goat ntany la tfeo n i l . panalo. ***** * * * * * * * * * ** API 05401 ! Copy froia D* 3trc0P for Information of Members and Associates cf Medical Advisory Committee. ____________________________________________ _______________ 9.-U-32 REPORT OF SUBCOMMITTEE ON CARCINOGENIC ITT TO THE MEDICAL ADVISORY COMMU T ES, API - SEPTEMBER 25, 1952 1 - The Subcommittee on Carcinogenicity has held no stated meeting since its last meeting in Cincinnati April 18, 1952, which action has been approved by letter ballot. 2 - The R.P.A. Committee held its third meeting at Bettering Laboratory on July 10, 1952, the minutes of which have been circularized to all members and associates of the Medical Advisory Committee and which minutes have been approved by the subcommittee by letter ballot. 3 - The research project (MC-1) has been continued on about the same scope as it has been during the past two years but with better results from the standpoint of quantitative mouse testing. Data sheets on various mouse experiments were mailed by Dr. Horton on July 16, 1952, to members of the Medical Advisory Committee, who also have received from Dr. Horton prior to this meeting a tabular sumnary of the current and completed biological experiments. 4 - Dr. Horton will present an interim progress report as part of this report. 5 - The subcommittee recommends that the various medical directors on the Medical Advisory Committee cooperate more fully by submitting the data requested by Dr. Phair in connection with the epidemiological survey and particularly the data concerning current cases. 6 - Dr. J. J. Phair will present as part of this report: a. A progress report on the epidemiological studies. b. Dr. Kehoe's decision as to whether or not Kettering Laboratory would be willing to undertake a critical review, with abstracts, of the literature on cancer as related to petroleum and his estimate of the additional cost if undertaken. 7 - With respect to the epidemiological survey (See Exhibit A) amor employees of customers, the letter ballots of the members of the subcommittee showed sufficient differences of opinion to warrant referral of this subject back to the subcommittee for further consideration. (Some letter ballots not received as of 9/10/52, but final tally will be available for the Chicago meeting.) 8 - The subcommittee by letter ballet approved of continuing Research Project MC-1 at approximately its present scope and cost ($100,000 per year) for the year beginning July 1, 1953. However, a few members recommended that the general level of research activity and the budget be decreased. API 05402 / -2- Dr. Eshoe will submit for this meeting an estimate of the budgetary requirements subdivided insofar as possible in terms of scientific objectives. 9 - Beeommendations, if any, eventuating from the meeting of the Research Project Advisory Committee to be held on September 2k, 1952. Respectfully submitted, M. N. Newquiat, Chairman. API 05403 API - MEDICAL ADVIS CRY COMMITTEE ACTIONS WITH RESPECT TO CANCER REGISTRY Macting - April 28, 19U7 - Buffalo. Nev York page 2 of Minutes, Item D, Report of Subcommittee on Carcinogenicity "Establish a registry of malignancies to report to the Subcommittee on Carcinogenicity. This registry would collect data on all malignancies incident in employees of the petroleum industry. It would set up its own procedures, forms, extent of data, follow-ups, pathology, treatment, outcome, autopsy reports, etc. after consultations with existing rogistries." c.*venth Meeting - April 2, 19^8 - Boston. Massachusetts Page 3 of Minutes, Item 3, Report of Subcommittee on Carcinogenicity "The committee reconsnended that Dr. Robert A. Kehoe and his associates collaborate with the Chairman of the Subcommittee on Carcinogenicity and as many members as is necessary in the preparation of a plan of collecting statistical medical information on cancer in the petroleum industry versus the country at large; and if possible versus other industries. The committee also recommended that a definite proposal be made for implementing the collection and coalition of such information (every effort should be made to separate any cancers caused by contact with known products from those arising from other causes)." Slghth Meeting - November 12, 19^6 - Chicago. Illinois Page 2 of Minutes, Item 5-d, Report of Subcommittee on Carcinogenicity Tho carcinogenic program -- at the University of Cincinnati should include: "Epidemiological studies of this problem in the industry." Tenth Meeting - November 11, 19^9 - Chicago, Illinois Appendix A, 3rd paragraph, Report of Subcommittee on Carcinogenicity "Dr. J. J. Phair, Professor of Preventive Medicine, Univorsity of Cincinnati, discussed the epidemiological aspects of this problem. 3e proposed the establishment of a cancer register at the University of Cincinnati to serve the petroleum industry and submitted a draft of a form to be used in obtaining the necessary morbidity information. It was agreed that legal advice should be obtained as to whether reporting such cancer cases to the University cf Cincinnati would be an invasion of the patient's rights." Meeting - Subcommittee on Carcinogenicity - August 26. 19^7 - New York, New York Page 2 of Minutes, Item 6-(a) "It is desirable to assemble data regarding (1) nature, (2) frequency and (3) duration of exposure of employees and customers to intermediate or commercial products containing as a constituent heavy catalytic distillates or residua which contain fractions boiling above 700 F. Also, to obtain the number of (1) employees and (2) customers so exposed. In order to obtain uniformity, Dr. Woody will outline the procedure for survey and approach the companies to conduct the above survey." API 05404 API 05405 REPORT OP SUBCOMMITTEE ON CARCINOGENICITY TO THE MEDICAL ADVISORY COMMITTEE, A.P.I., - SEPTEMBER 25, 1952 . . The Subcommi ttee on Carcinogenicity has held no stated Beetl ing since its last meeting in Cincinnati April 18, 1952, which action has been approved by letter ballot. The R.P.A. Committee held its third meeting at Kettering Laboratory on July 10, 1952, the minutes of which have been circularized to all members and associates of the Medical Advisory Committee and which minutes have been approved by the Subcommittee by letter ballot. 3 - The research project (MC-1) has been continued on about the same scope as it has been during the past two years but with better results from the standpoint of quantitative mouse testing. Data sheets on various mouse experiments were mailed by Dr. Horton on July 16, 1952, to members of the Medical Advisory Committee, who also have received from Dr. Horton prior to this meeting a tabular summary of the current and completed biological experiments. ll - Dr. Horton will present an interim progress report as part of this report. 5 - The subcozanittee recommends that the various medical di rectors on the Medical Advisory Committee cooperate more fully by submitting the data requested by Dr. Phair in connec tion with the epidemiological survey and particularly the data concerning current cases. 6 - Dr. J. J. Phair will present as part of this report: a. A progress report on the epidemiological studies. b. Dr. Kehoe's decision as to whether or not Kettering Laboratory would be willing to undertake a critical review, with abstracts, of the literature on cancer as related to petroleum and his estimate of the additional cost if undertaken. 7 - With respect to the epidemiological survey (See Exhibit A) API 05406 T/ -2- among employes of customers, the letter ballots of the members of the subcommittee shoved sufficient differ ences of opinion to varrant referral of this subject back to the subcommittee for further consideration. (Some letter ballots not received as of 9/10/52, but final tally will be available for the Chicago meeting) g . The subcommittee by letter ballot approved of continuing Research Project MC-1 at approximately its present scope and cost (#100,000 per year) for the year beginning July 1, 1953* However, a fev members recommended that the general level of research activity and the budget be decreased. Dr. Kehoe will submit for this meeting an estimate of the budgetary requirements subdivided insofar as possible in terms of scientific objectives. 9 - Recommendations, if any, eventuating from the meeting of the Research Project Advisory Committee to be held on September 2l{., 1952. Respectfully submitted, H. N. Newquist, Chairman. II API 05407 * / API - Medical Advisory Committee ACTIONS WITH RESPECT TO CANCER REGISTRY r fi ----i-pf-l-t-inK - April 28, 19117 - Buffalo, New York ^ pftge 2 of Minutes, Item D, Report of Subcommittee on Carcinogenicity gstablish a registry of malignancies to report to the Subcommittee jp Carcinogenicity. This registry would collect data on all mal I gnancies incident in employees of the petroleum industry. It yould set up its own.procedures, forms, extent of data, follow-ups, oftthology, treatment, outcome, autopsy reports, etc. after consultations with existing registries." .,,th Meeting - April 2, 191i8 - Boston, Massachusetts page 3 of Minutes, Item 3# Report of Subcommittee on Carcinogenicity "The committee recommended that Dr. Robert A. Kehoe and his associates collaborate with the Chairman of the Subcommittee on Carcinogenicity and as many members as is necessary in the preparation of a plan of collecting statistical medical informa tion on cancer in the petroleum industry versus the country at large; and if possible versus other industries. The committee also recommended that a definite proposal be made for implementing the collection and coalition of such information (every effort should be made to separate any cancers caused by contact with known products from those arising from other causes)" riith Meeting - November 12, 19li8 - Chicago, Illinois Page 2 of Minutes, Item 5-d, Report of Subcommittee on Carcinogenicity "The carcinogenic program -- at the Univ. of Cincinnati should include: "Epidemiological studies of this problem in the industry." I liath Meeting - November 11, 19li9 - Chicago, Illinois Appendix A, 3rd paragraph, Report of Subcommittee on Carcinogenicity "Dr. J. J. Phair, Professor of Preventive Medicine, University of Cincinnati, discussed the epidemiological aspects of this problem. He proposed the establishment of a cancer register at the University of Cincinnati to serve the petroleum industry and submitted a draft of a form to be used in obtaining the necessary morbidity information. It was agreed that legal advice should be obtained as to whether reporting such cancer cases to the University of Cincinnati would be an invasion of the patient's rights." - Subcommi ttee on Carcinogenicity - August 26, 19ii7 - New York, N.Y. Page 2 of Minutes, Item 6- (a) "It is desirable to assemble data regarding (1) nature, (2) frequency and (3) duration of exposure of employees and customers to inter mediate or commercial products containing as a constituent heavy, catalytic distillates or residua which contain fractions boiling above 700F. Also, to obtain the number of (1) employees and (2) customers so exposed. In order to obtain uniformity, Dr. Woody will outline the -- ' '1 API 05408 ,,, ,N S LARORATORT ^ g f MEDICINE-- EDEN AVENUE aT1 19. OHIO UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH September 20, 1952 CARLE ADDRESS: KETLAR. CINCINNATI TELEPHONE: CAPITOL MM Mr* D. V. Stroop American Petroleum Institute 50 West 50th Street New York City 20 Dear Mr. Stroop: I am sending you herewith, for your information, a statement of expenditures made on behalf of American Petroleum Institute during the second quarter of 1952. (This statement- does not include the amount of $50,000.00 which was received on July 18.) I believe the statement is self-explanatory, but if you have any questions or comments, Doctor Kehoe would appreciate your bringing them to his attention. Very truly yours, ef Inc. x j t . iLenoe API 05409 MEMORANDUM FROM THE KETTERING LABORATORY FOURTH MEETING OF THE ADVISORY COMMITTEE A_PI~-R-ESE1AR-CH PROJECT .. MC-1 .. I,I\!i' n x . Chicago, Illinois September 2k V A , Biological Testing of Refinery Intermediates and Products. The main emphasis is being placed currently on raw lubricant stocks. Selected samples of such straight run distillates -*ave been analyzed spectrophotometrically and classified according to spectrum type (Type C includes those which show a definite absorption maximum at 1j28U36 n y i ; Type B are those which show no maxima in their absorption curve but do exhibit an inflection at approximately 385 myi ). No straight run distillate containing seme material boiling above 800F. has yet been found which could be classified as Type A (no Inflections nor maxima in its absorption spectrum indicative of three to six ring aromatic hydrocarbons). Further, the untreated Type B and Type C oils on which mouse tests have been completed have demonstrated moderate carcin ogenic potencies (PMC ~ 0.1) in this laboratory. However, reports from other research organizations have indicated the possibility that some straight run distillates in this boiling range may have no more than a negligable potency to mioe. Highly refined white oils have exhibited no tumor inducing character whatsoever under conditions of testing comparable to those used for the untreated distillates Such white oils, of course, show very little, if any, absorption API 05411 * - 2- in the 350-14-50 m ji region. However, this lack of spectral absorption is not, by any means, a necessary specification for a non-carcinogenic lubricant. The solvent-refined product, API-100, still absorbs radiation of these wave lengths almost as strongly as the straight run distillates tested, but has not induced a single tumor in C3H mice in the course of a year of repeated applications. This result is contrasted with that on API-99 (Pm c s 0 * 0 7 ) , a lubricant I of similar viscosity, which had been only mildly acid-treated in its refining. In investigating further th9 etiology of the cases of scrotal carcinoma among wax pressmen, the mouse test would appear to be a very useful tool. It may be possible to determine whether the lack of difficulty in many refineries can be related to the non-carcinogenicity of the paraffin distillates employed or if the whole answer lies in the I precautionary measures being taken, along with other factors, such as low susceptibility to the disease on the part of certain types (races, etc.) of employees. The preliminary indications are that weakly carcinogenic lube stocks can be handled safely so long as reasonable precautions are taken to prevent prolonged or frequent exposure on the part of the workmen. In addition to the mouse tests on lube stocks, a large number of experiments are being carried out on cracked streams already subjected to a preliminary biological screening test. The purposes of these observations are described in the following sections of this memorandum. API 05412 I A _ B. Biological Methods for Measuring the Relative Potencies of Petroleum Stocks under Various Conditions. Since the expansion of the biological testing pro gram in 19U-9 all results of experiments on oils have been related to those of tests on an external reference standard, the synthetic polycyclic methylcholanthrene. Three different frequencies of exposure have been employed in covering the wide range of potencies of the refinery streams which have been examined. For various reasons, it has been assumed that the mechanism of the cancer-inducing action of most hydrocarbontype oils was the same as that of the reference standard and hence that the translation of the results of experiments involving one, two, or three applications of oil per week to a common potency (Pjic) seal was justified. A number of experiments have been started in 1952 to determine whether this assumption was valid. It will be apparent from Figure 1 that it was necessary to select oils with potencies in the range, 0.10 to 0.16 , if satisfactory tests at all three frequencies of application were to be obtained, Hence, API-63, a catalytically cracked residuum, and API-113, a blended industrial fuel oil, were chosen for the current experiments. The preliminary results are in line with the expectation that PMC values are Independent of the frequency at which the oils are applied to the mice. API 05413 AVERAGE LATENT PERIOD FOR TUT'OE INDUCTION (weeks) ) ") ) h'lgurs 1 --ItiJLATiOH OK AVkiHKOL: L.K'1`k M 'K l-LiHlWV) L E CI E N D SYMBOL STRAIN OF MICE NUMBER OF APPLICA TIONS PER WEEK DOSAGE PER APPLICA TION (mg.) a C3H 1 100 k C3H 2 100 C3H 3 100 CFW 3 100 + C3H 1,2,3 20 '\13 0.10 API 05414 0.20 0.30 o.lfO _L o .5o o .6o RELATIVE CARCINOGENIC POTENCY,Pnc 0.70 0.80 0.90 ) ) T 11 Since the amount of oil applied upon the skin of a mouse with a camel's hair brush cannot be held exactly constant, experiments have been started to determine the effect of the variable average dosage per application on the rate of induction of tumors by various types of carcin ogenic oils. "'ith solutions of the reference standard, methylcholanthrene in benzene, reduction of the average dose from 100 mg. to 20 mg. per application did not alter the rate significantly (see Figure 1). This comparison will be repeated with the new sub-line of the C3H strain which is now being supplied by the Jackson Memorial Laboratory. The methylcholanthrene will be purified by chromatography, etc., for the new tests to avoid complication by trace impurities. Similar results were obtained with the fuel oil, API-113. The rate of induction of tumors was found to be independent of the amount of oil per application within the range of 5 to 100 milligrams. Indeed,the average latent period for three experiments with API-113 on C3H mice, involving doses of 5 20, and 100 mg. per application, varied by less than one week (17.2-18.0 weeks). Since many of the fuel oil blends tested on other projects have proven excessively toxic to C3H mice, this was a welcome finding. Thus the systemic toxic effects accompanying the employment of a heavy fuel oil i *- an experiment of this type may be minimized by reducing the total quantity of oil applied without delaying the induction of tumors significantly. API 05415 ! - 6- In contrast to the foregoing results on standard methylcholanthrene solutions and fuel blends, two tests on the highly potent catalytically cracked residua, API-8 and 71, have indicated .hat the rate of induction of tumors with these materials is strongly dependent on the amount of oil involved in the individual application. The presence of accelerating constituents in these oils, particularly in API-71, had previously been suspected on the basis of fractionation studies and related biological test's. It should be possible now to determine by biological testing the critical level of concentration for the action of such a material. To this end, experiments have been started on API-3 at three dosage levels (5, 20, and $0 mg. per application). Experiments are also being started with distillate fractions, boiling at 14.65 to 690 F., of API-71, from which polycyclic compounds containing more than two aromatic rings have been removed by chromatography. These fractions will be tested in such a manner as to determine which, if any, demonstrate the type of irritating and accelerating properties exhibited by various dodecylbenzenss. The average time required for the development of grossly malignant changes in tumors induced by a carcinogenic oil seems to be related inversely to the degree to which the oil has these specific irritating properties. In a number of experiments, further relationships have been noted between the absorption spectrum of the oils and this "delay period" . These findings are being developed further in connection with the analytical tool. API 05416  \ - 7- Qt Development of Rapid Methods for Estimating the Relative Carcinogenic Potency of Any Given Refinery Intermediate or Product. Continued efforts to relate the observed carcinogenic potencies of the large number of refinery streams which have been tested on mice to certain of their physical and chemical properties have led to a working hypothesis concerning the tyoes of compounds responsible for the physiologic action of these complex oils. It has been postulated that, primarily, II their cancer-inducing action dependsupon the presence of specific polycyclic aromatic hydrocarbons containing three or more rings. The isolation of the 5-r inged compound ^ /v V I 3,lj.-Benzpyrene 20^12^ from the FCC cracked residuum, API-8, provided evidence that the carcinogenic structures in such petroleum products may be identical to those in coal tars. From the available chemical and biological data, there is every reason to believe that an Important contribution to the observed potencies of cracked products is also being made by certain polycyclic hydrocarbons of lower molecular weight than benzpyrene. API 05417 - 8- The second basic postulate is that the rate of induction of tumors by a refinery stream depends not only upon the concentration and activity of specific polycyclic carcinogens, but also upon the concentration of non-carcin ogenic but accelerating constituents such as certain long chain alkylbenzenes. Under certain conditions, it is felt that the effect of such constituents on the rate at which an oil will induce tumors in mice may be much greater than that of even the necessary carcinogens themselves. The third important mechanism operating to modify the normal physiological action of an oil containing carcin ogenic hydrocarbons would appear to be an inhibitory one. It is necessary to postulate this type of mechanism to explain the lack of potency of certain crude oils and reduced crudes to mice. The inhibitory components are probably contained in the highest boiling ends of these crudes and could well be non-hydrocarbon in composition. The relative potency of a given oil is thus con sidered to be the resultant of three semi-independent vectors, the effective concentrations of the carcinogens, the accel erators, and the inhibitors. Fortunately, the third factor can probably be safely neglected for most refinery streams, excepting crude oils, reduced crudes, and cracked residua from viscosity breaking operations. Hence our efforts along chemical lines are being directed toward the identification of the carcinogens and the accelerators responsible for the demonstrated potencies of the available samples of cracked products and straight run distillates. API 05418 > * -9 - The levels of concentration of 3i+-bnzpyrene in the fractions of catalytically cracked residua which boll above 900F., as estimated from fractionation studies made in the laboratory, are more than enough to explain the observed potencies of these cuts. Hence, current work is being centered on fractions which boil in the 700-900 range, to identify or classify the structure of carcinogens respon sible for the very significant potency of these fractions. All of the materials which would react with maleic I anhydride, including anthracenes, benzanthracenes, naphtho- pyrenes, 6,7 -benzoquinolines, etc., have been exhaustively extracted from the FCC cracked residuum, API-8, for mouse testing. The extent of the contribution of phenanthrene and fluorene derivatives to the potency of a similar catalytically cracked product is also being determined by animal testing. Additional biological experiments are planned, employing fractions in which certain classes of J^-ring hydrocarbons have been concentrated by the techniques of vacuum fractional ' distillation, chromatography, and liquid thermal diffusion. The most reliable semi-empirical correlations between potencies and physical properties of oils, which have been developed in this and in other laboratories, have depended upon ultraviolet spectra in the 36O-I4.50 mjul range. 3,Ij.-Benzpyrene and Anth&nthrene (one of the Dibenzpyrenes) have characteristic absorption bands in this range (383 I and 14.29 m^u , respectively, in isooctane). It is felt that the success of these methods depends rather strongly upon API 05419 i ) - 10- the degree of influence of pyrene-type carcinogens upon the potency of any particular oil in question. iVhere carcinogens of lower molecular weight are of predominating importance and where the concentration of monocyclic aromatic hydrocarbons with specific irritant properties becomes significant, as could be true in the case of cracked or straight run dis tillates, boiling $ 0 Q -7 $ Q F ., these methods have not proved to be satisfactory. Thus, although the potency of the San Joaquin (California) distillate, API-79# 86 percent of which 1! boils above 750F., was predicted very closely on the basis of the absorption band at 1*29 /U that of the West Texas distillate, API-105* 73 percent <75 0 # was very much higher than was indicated by spectrophotometric data. Similarly, ' one of the very few incorrect predictions of the potency of a catalytically cracked residuum was that for the TCC product, API-71, an oil containing an unusually large colorless fraction, II boiling 500-750F. A s previously mentioned, a number of cuts have been prepared from this fraction to narrow down the search for possible accelerating irritants. Since 3, i*-benzpyrene seems to be an important component of the majority of the petroleum stocks which have been carcinogenic to mice, some effort is being given to the development of a reasonably rapid method of analysis for this compound. The major problem involves its separation from the non-carcinogenic isomer, perylene, which is usually i present in higher concentration. API 05420 t # - 11 - Correction factors for physical properties such as viscosity, mid-boiling point, etc., have been discussed at length. Some preliminary animal tests have been started to determine whether the viscosity of an oil is an important factor in determining the rate at which it induces tumors, A straight run distillate (viscosity, 235 SSU/100P.) is being compared with a 5 percent solution of a polymer of an alkylstyrene in the same distillate, the viscosity of the material having thus been raised to 175& SSU/100P. If the solution containing the polymer has a significantly different potency than the virgin distillate, it will of course be necessary to be sure that the polymer itself has no effect on the skin before the difference can be attributed to a purely physical change in the oil. I API 05421 * - 12 - prom the Kettering Laboratory, College of Medicine, University of Cincinnati, Cincinnati, Ohio Investigative Team: Frank P, Cleveland, M.D. Ralph T. Denham, B.S. Frank R. Dutra, M.D. Mary Jane Graf, B.S. Francis F. Heyroth, Ph.D., A. Wesley Horton, Ph.D. John J. Phair, M.D. Ruth C. Pierle, Ph.D. Helen . p]gge, B.S. Fred Shaffer, M.S. Raymond R. Susklnd, M.D. Dorothy A. Templeton, B.S. Russell Tye, M.S. Waldo J. Younker, M.S. Effie Bright Anna Marie Gross Lea Murbach M.D. Report: A. Wesley Horton, Ph.D. Date; September 2li. 1952 Director API 05422 i For Information Only - Not for Publication FI Research Project MC-1 TABULAR SUMMARY OF CURRENT AND COMPLETED ! BIOLOGICAL EXPERIMENTS ' The Kettering Laboratory in the Department of Preventive Medicine and Industrial Health College of Medicine University of Cincinnati Cincinnati, Ohio API 05423 t i INDEX Index to Processes Page Number 1 Index to Table I 2 Table I - Skin Painting Experiments on High 5 Boiling Samples Table II - Concentration Standards Concentration Standards with Methylcholanthrene in Benzene 22 Concentration Standards with Synthetic Carcinogens in ' Dodecylbenzene 2k Concentration Standards with Methylcholanthrene in Sec,-amylbenzene 25 Concentration Standards with Synthetic Carcinogens in Various Solvents 26 Control Experiments with Various Solvents 27 Experiments Employing a Limited Number of Applications of Methylcholanthrene in Benzene 28 II Table III Experiments on Acceleration of Carcinogenesis by Specific Solvents 29 Table IV - Experiments on Retardation of Tumor Formation 3y Washing 31 Individual Data Sheets on Completed Skin Painting Experiments 3l|. API 05424 - 1 - INDEX TO PROCESSES Process Appendix Page Number Non-catalytic cracking of virgin gas oil Non-catalytic cracking of catalytic gas oil Steam cracking Viscosity breaking Dubbs coking 3atch coking Delayed coking Naphtha reforming Polyforming Hydroforming Thermofor catalytic cracking (T. C. C.) Fluid catalytic cracking (F. C. C.) Houdry Cycloversion Solvent extraction Straight run distillation Fractional distillation Lubricating oil Wax pressing MEK - Benzol solvent dewaxing Filtration dewaxing Desulfurization by catalytic hydrogenation Acid treating Viscosity effects Fuel oil blending Fractional distillation of API-8 Diels-Alder reaction Solvent extraction with concentrated HgSO^ * Air oxidation Chromat ography 5 5 8 8 8 9 9 10 10 10 11 12 15 15 16 17 17,18,21 18 18 18 19 19 19 19 19 20 20 20 21 21 API 05425 API Sampl T 2 6 8-3 8-i 8-f 8-6 8-7 8-8 8-9 8-10 8-11 8-12 8-12a 8-13 8-la 8-1$ 8-16 8-17 8-18 8-19 8-20 8-21 8-22 8-23 9 10 11 12 12-2 12-i|. 12-$ 12-6 12-7 1$ 16 17 18 19 20 20-1 21 22 ) INDEX TO TABLE I Process Straight run distillation Non-catalytic cracking of virgin gas oil T. C. C. F C C Straight rim distillation Non-catalytic cracking of virgin gas oil T. C. C. F. C. C. Filtration dewaxing Dilution of No. 8 Chromatography Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Diels-Alder reaction Fractional distillation of No. 8 Fractional distillation of No. 8 Fractional distillation of No. 8 Dilution of No. 8 Chromatography Fractional distillation of No. 8 Solvent extraction with concentrated HgSO]^ Solvent extraction with concentrated HgSOjT Dilution of No. 8 * Chromatography Diels-Alder reaction T. C. C. T. C. C. Houdry F. C. C. Chr omat ogr aphy Distillation (1 plate vacuum) Distillation (1 plate vacuum) Distillation (1 plate vacuum) Fractionation Polyforming Solvent extraction Solvent extraction Solvent extraction Solvent extraction Viscosity breaking Naphtha reforming Non-catalytic cracking of catalytic gas oil Dilution of No. 20 Desulfurization by catalytic hydrogenation Cycloversion Appendix Page Number 17 5 11 12 17 5 li 13 19 13 21 20 20 20 20 20 20 20 20 20 20 20 13 21 20 20 20 13 21 20 11 11 1$ 13 21 21 21 21 20 10 16 l6 16 16 8 10 5 $ 19 1$ * Experiments which are complete, including micro- . ' . pathology, are indicated by an asterisk in the body ^ of the tables. API Sample number 25 25-1 20 27 28 29 30 31 32 % 35 30 37 38 ?9 j ft -1 t ft b-9 50 I I H 57 58 9 60 61 62 $ I 67 68 69 70 ) > - 3 - I.'.PEX TO TABLE I Process F C C Solvent.extraction rith concentrated HgSOji Solvent extraction 1 ith concentrated HgSoj Non-catalytic crackiig of catalytic gas oil Distillation Dilution of No. 25 F. C. C. Solvent extraction Delayed coking Catalytic feed to non-catalytic cracking Non-catalytic cracking of catalytic gas oil T. C. C. Wax pressing Delayed coking Houdry Non-catalytic cracking of catalytic gas oil T. C. C. Polyforming Catalytic feed to non-catalytic cracking Non-catalytic cracking of catalytic gas oil T. C. C. Delayed coking F. C. C. F. C. C. MEK - Benzol solvent dewaxing F. C. C. Non-catalytic cracking of catalytic gas oil F. C. C. Non-catalytic cracking of catalytic gas oil F. C. C. Hydroforming Houdry Houdry Dubbs coking Dubbs coking Catalytic feed to non-catalytic cracking Non-catalytic cracking of catalytic gas oil Straight min distillation Wax pressing Naphtha reforming Non-catalytic cracking of virgin gas oil T. C. C. Non-catalytic cracking of catalytic gas oil Acid treating Houdry Non-catalytic cracking of catalytic gas oil Non-catalytic cracking of virgin gas oil Viscosity breaking Viscosity breaking F. C. C. Polyforming Solvent extraction ApI o5427 Appendix Page Number 5,12 20 20 6 17 17 13 16 l 11 18 61 15 11 10 6 6 11 10 13 13 18 7,12 10 15 15 8 8 7 7 17 18 10 5 11 7 19 7,15 7 5 8 8 Ik 10 16 API Samp Ie Member 71 71-1 71-2 72 % 75 7b 77 78 79 81 82 83 83-1 83-2 8 35 86 87 88 89 90 91 92 93 9h 96 97 98 99 100 101 102 103 lOlj. 105 108 109 110-1 1 1 1 -k in -6 111-7 112-1 112-3 Sf iik-i 115 ) -k - > INDEX TO TASLS I Process T. C. C. Chromatography Chromatography Non-catalytic cracking of P. C. C. Delayed coking Solvent extraction Naphtha reforming Hydroforming T. C. C. Straight run distillation Houdry T. C. C. Air oxidation Air oxidation Chromatography Delayed coking F. C. C. Steam cracking Batch coking F. C. C. F. C. C. Delayed coking F. C. C. Non-catalytic cracking of Non-catalytic cracking of Non-catalytic cracking of Delayed coking Delayed coking Delayed coking Lubricating oil Lubricating oil F. C. C. F. C. C. Delayed coking F. C. C. Straight run distillation Non-catalytic cracking of T. C. C. Fractional distillation Fractional distillation Dilution of No. 111-ij. Dilution of No. 111-q. Fractional distillation Fractional distillation Fuel oil blending Straight run distillation Viscosity effects Straight run distillation virgin gas oil ' ' catalytic gas oil catalytic gas oil virgin gas oil virgin gas oil API 05428 $ - ;> - TABL3 I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES PROCESS API SAMPLE NUMBER PRODUCT Uon-cataly tic cracking of 2 Cracked sidestream ANA LY T ICA L DA TA DISTILLATION (2mm corr. to 760mm) GRAV ITY VISCOSITY <7SCF (%) 750 925* >925 E.P. (#) (#) (P.) 21.2 33/100 SSU 6 59 65 72 91; 108 Cracked residuimi Cracked residuum Cracked residuum Cracked residuum Cracked residuum Cracked residuum 5.2 33 26 4-1 - 8.5 32 - 6.6 163.5/100 4-3.8 29.9 26.3 SSU 9.6 37.1/122 35 37.5 27.5 - SSP 10.1; 31.7/122 35 4-8 17 - SSP 2.3 1530/ 130 32 25.5 IlL.9 - SSU Non-catalytic cracking of catalytic gas oil 20 Cracked residuum i;.7 132/ 122 51 33 16 - SSP Dilution of No. 20 20-1 50# oil No.20; 50# dodecyl- benzene Non-catalytic 23 PCC gas oil cracking of feed catalytic gas oil 26.7 55.5/100 78.5 20.6 SSU .9 838 API 05429 ---------- > -5 - TABLE I S O PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES ^-- B I0L 0G ICAL DA TA STRAIN i ' cu OP MICE AND NUMBER OP APPLICA TIONS PER WEEK K I W S3 04 O M M Eh ORIGINAL s5 NUMBER < O CO M OP QO MICE PINAL EFFEC TIVE NUMBER OP MICE MAXIMUM INCIDENCE OP TUMORS (T.I. /weeks' AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 2 C3H 1 100 20 0/75 - RELATIVE CARCINOGENIC POTENCY, pmc - 6 CPW 3 100 30 59 C3H 3 100 20 65 C3H 3 100 20 72 C3H 3 100 20 9U- C3H 3 100 20 108 C3H 3 100 20 108 C3H 3 5 20 20 CFW 3 100 20 20 C3H 3 100 20 20-1 CPW 3 100 20 21 76/30 11 82/69 9 89/29 15 73/18 10 60/39 7 71/28 20 0/3 15 100/22 10 90/21 17 100/25 20*5-i W.7ll3 o.o6l;o3 - - 20. ^ -.0 1 13.711 vo.i7i:^ 25:i3 2 1.8^ - 13 .7!? 17.1 0.08^ g J ,+.01 0.1-.0 2 aj O.lll.02 o.wio! i u .i u ! 0.10l ;02 23* CPW 3 100 20 23* C3H 2 100 20 20 100/19 18 9V28 10I 1 7 .2^2 _ ^O.lS-Ioi Number alive after 52 weeks. API 05430 - n t TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES A N r~p PROCESS API SAMPLE NUMBER PRODUCT Non-catalytic cracking of catalytic gas oil m n it tt tt m m 2k Cracked residuum from No. 23 29 TCC gas oil feed 30 Cracked residuum from N o . 29 3*4- Houdry gas oil feed 35 Cracked residuum from N o . 3I4. 38 Total crack ing charge; combination unit 39 Cracked residuum from No. 38 k k PCC decanted oil feed kS Cracked residuum from No. 14t DISTILLATI^ (2mm corr. to 7 GRAV ITY VISCOSITY 750. S I l (%) 5.9 5 1 .9/210 32.3 3I4..6 33.! SSU 15.7 70/ 100 SSU 8.5 10/210 26 SSP 28.0 k 7 . 5/100 SSU 2.7 2320/100 35 37 SSU 16.1 32.2 23.3 i+3.1 7.8 1 7 7 / 1 2 2 31.0 19.8 4-8.U SSF 15.2 -1.7 2 k 1 /100 SSU 179/122 SSP API 05431 I '- 6 - TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES -- STRAIN OP MICE 1 fr. bO <5 b i o :L 0 G I C A L DA T A AND K PINAL AVERAGE NUMBER w a fr O EPPEC- LATENT OP H ORIGINAL TIVE W EH MAXIMUM PERIOD RELATIVE P API APPLICA- O < NUMBER NUMBER INCIDENCE FOR TUMOR 3ARCIN0GENIC SAMPLE TIONS < O CO w OP OP OP TUMORS INDUCTION POTENCY, P. liUMBEP PER WEEK O J MICE MICE T.I./weeks) (weeks) Q fr PMC 2i+ CPW 3 100 19 18 100/15 8.51 - 29 C3H 1 100 20 19 30* C3H 1 100 20 13 3 k * CPW 3 100 18 17 35 CPW 3 100 20 15 38 CPW 3 100 20 13 81+/30 92/33 9U/32 87/20 62/58 19-31 21+t^ 19.5!J 2 9 -3 ^ n 3q+09 *39_.21 0.06 .01 o .o 9!:q2 39 CPW 3 100 20 11 S k /2 h 2i.s!f /\j 0.051.01 39 CPW 3 100 10 7 57/20 16.l4.iJ 1+1+ C3H 1 100 20 16 9I+/I4.O 27^ 1+5 C3H 1 100 20 9 89/1+1 30*1* H O +CM1 O0 O API 05432 TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES A N A L Y T I :a l D A T A PROCESS API SAMPLE NUMBER PRODUCT Non-catalytic cracking of catalytic gas' oil If ft M m m i*6 FCC gas oil 'eed 1*7 Cracked residuum from No. 1*6 5k Total crack ing charge 55 Cracked residuum from No. Sk 61 Cracked residuum 63 Houdry gas oil feed DISTILLATIOBj ] (2mm corr. t0 76oJ GRAV ITY VISCOSITY <750 (%) 750 925 >925 B. }\ <*> (*) (0y 87.9 12.1 0 780 76 15.5 8.5 I 1 33.0 i*.2 7.8/122 93.9 l*.l 2.0 822 SSF 18.8/122 55.9 26.1 18 I SSF 6.3 25.6 73.6/100 66.8 18.2 15 1 SSU 25.7/100 1*8.5 37.6 13.9 I SSU n 6i* Cracked 19.9 3 1.8/100 52.5 31.8 15.7 m 1 residuum SSU from No. 63 fl 91 FCC gas oil 20.1* 57.8/100 80.1 17.9 2.0 830 feed SSU API 05433 I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES -- API SAMPLE iUMBER STRAIN OP MICE AND NUMBER OP APPLICA- TIONS PER WEEK B" I" L O \T I r T i n r m a t ocsj a a, O H O < <5 u 50 5 h g ORIGINAL NUMBER OP MICE PINAL EPPEC- TIVE NUMBER OP MICE MAXIMUM INCIDENCE OP TUMORS (T. I ./weeks' ---------- AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, *MC 1*6* CPW 3 100 20 15 100/ 2 k 1 6 J o.o9i:8i 14.7 CPW 3 100 20 Ik 93/17 1 1 .6^ 5k CPW 3 100 20 16 100/36 2 3 .k ll A / 0.O4..OI 55 CPW 3 100 19 15 87/21 13.2 m 0 . 12 ! : ^ 61 CPW 3 100 20 17 88/26 13.6 ,n , o+.02 'v/0*12-.06 63* C3H 3 100 20 18 89/26 19!? n 11 52+- .*0021 63 C3H 1 100 20 19 37/36 - - 63 C3H 2 100 20 18 100/33 2 1 .8^ 63 C3H 3 100 19 15 6i|.* C3H 3 100 20 13 IOO/19 100/23 15.^1 I5 .a ;f 0.1 5 .0 1 n .1 +.01 *1^ -.02 91* C3H 2 100 20 19 95/23 16.1 0.1 9 1 .0 1 API 05434 -ri- TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES A N A L Y T I CAL D A T A DISTIJn a t i o n 1 2mm 3orr. 760maJ w PROCESS API SAMPLE NUMBER PRODUCT Non-catalytic 92 Cracked cracking of residuum catalytic from No. 91 gas oil a 93 Cracked residuum GRAV ITY VISCOSITY <750 (*) 750 925 >925 (*) (*> E.P. | F0J i 6 .1 102.5/100 70.5 27 SSU 2.5 p 7.9 I*9 .i*/100 87 l*.5 8.5 1>4 SSU I - Steam cracking Viscosity breaking m m Dubbs coking n 86 Cracked residuum 3.5 5000/ 100 51.9 28.1* l8x 880lM SSU 18 Cracked residuum from No. 17 3.1 1123/210 23.7 21* 52.3 SSU i 66* Cracked 6.5 residuum 67a Cracked side 15.6 stream from fractionator producing No. 66 18/210 22.1 29 1*8.9 SSP ' 81/000 81*.6 10.7 1*.7 SSU 1 52* Cracked sidestream 53* Blowdown oil 21.0 10.5 1*3.5/100 SSU 203/ 100 SSU 95.2 2.5 2.3 6I .3 23.3 15.1* - 1 tm 1 Distillation stopped when cracking occurred. a Peed to unit included catalytically cracked components. API 05435  I - - 8- . TABLE I <! SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES API SAMPLE NUMBER STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK 92 C3H 2 BIO 1 ^ 5! ce H 25 Oh O ta H Ej ORIGINAL o <4 NUMBER <4 o CO H OF O J q a. MICE L 0 G I C A L DA FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS CT.I. /weeks) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 100 20 A 78/23 RELATIVE CARCINOGENI POTENCY, PMC nJ 0_.21+..0Q25 93 C3H 3 100 20 18 914-/30 27.3-1 0.0 7 1 .0 1 86 C3H 1 100 20 17 100A9 35:? rJ 0.1 2 . >02 18 CFW 3 100 10 9 56/30 18-i1 -7i:o5 18 CFW 3 100 20 6 50/25 - - 66 C3H 2 100 20 19 100/37 28.2+f *>0.111.0 1 67 C3H 2 100 20 13 77/17 1 1 .7^1 - 52 CFW 3 100 20 15 I 87/36 19.7!];1 53 CFW 3 100 20 20 100/15 8-1 API 05436 - 9 - TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES A N A L Y T I CAL data PROCESS API SAMPLE NUMBER PRODUCT Batch coking 87 Cracked sidestream GRAV ITY 14.9 DISTILLATION 2mm <sorr. 760aai VISCOSITY 750 <750 925 >925 E.pJ (*) (%) (*) P.) 500/ 100 SSU Delayed coking m m n 28 Cracked 15.3 361/100 42.4 sidestream SSU 71; Total furnace 12.5 198/122 22.3 32.5 45.2 - charge SSP (including recycle) 33 Cracked side 16.8 1 3 1 .4/100 60 38.1 1.9 - stream from SSU No. 71; 81; Cracked sidestream 30.2 55/100 79 19.9 1 . 1 - SSU 90 Cracked sidestream 30.5 40.6/100 90.2 9.2 SSU .6 850 96 Cracked sidestream 33.2 43.7/100 77.7 22.2 SSU .1 92U 97 Total furnace 16.6 386/100 57.8 32.2 10 charge SSU (including recycle) 98 Cracked 31.0 38.1 /100 100 740 sidestream SSU from No. 97 API 05437 TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES --- - API ;a mple DUMBER - 87 STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK 1 < g W 55 (X, O M W E-* O < < o CO M O iJ Q fXi BIO 0RIGINAI NUMBER OF MICE C3H 3 100 20 l c g :[ C A L D J L T A FINAL EFFEC TIVE MAXIMUM NUMBER INCIDENCE OF OF TUMORS MICE !T.I./weeks! AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 12 17/5 - 1I 87 C3H 2 20 87 C3H 2 100 20 20 28* CFW 3 100 20 28 C3H 1 100 20 11 91/30 114- 14/11 19 84/15 19 a h /S i 20.5U - 1 0 .6 tf 24.2!^ 74 C3H 2 100 20 1 l6 9 k/b 7 29| RELATIVE CARCINOGENIC POTENCY, Pm c - r J 0.16.03 " - - ~>o.23i;gf 33* CFW 3 100 20 1 33* C3H 1 100 20 1 84 C3H 3 100 20 90 C3H 3 100 20 96 C3H 3 100 20 ! 97 C3H 3 100 20 18 95/15 19 95/30 19 95/24 17 100/38 15 93/27 15 87/22 8-1 1 5 .5 !? 15.6? 21.7^ 1 6 .2 j 16.3g o.56t:^ o-iSt'.os 0 .10 .0 2 O-^.'OE o .i b l - .o z 98 C3H 3 100 20 11 73/39 2t . 8 | 0 08*oi API 05438 O - 10 - t a b l j: i SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES __ A N A L Y T I C A L D A T T PROCESS Delayed coking N Naphtha reforming m n DISTILLATION (2m m corr. to 760m ^ API SAMPLE NUMBER PRODUCT GRAV ITY VISCOSITY <750' (*) 750925>925 (*) 103 Cracked sidestream k l Wax tailings, $ 0 $ benzene 19 Cracked residuum 58 Cracked residuum 76 Cracked residuum 25.2 1.2 17.0 6.3 30.6 135ss/u100 1 3 1 / 21^0 SSP 4-3*9 35.1 9.6 4-9.8 39.7/100 SSU 91 8.95 117/122 SSP 85 H 4..3 3s1/su130 rJ 91 8 Polyforming 13 Cracked residuum 10.1 ssu 15^/100 63 15 8901 . 37 Cracked residuum 11.2 ssu 60.2/100 66 15 19 8623 Hydroforming 69 Cracked residuum k9 Cracked residuum 77 Cracked residuum 15.9 10.1 22.8 ^ s3s/u130 75.1 ^95 8.3 16.6 3.3 100 1 Distillation stopped when cracking occurred. API 05439  * - 10 - TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES API SAMPLE number STRAIN OF MICE AND NUMBER OF APPLICA- TIONS PER WEEK B I (3 L 0 G i S.SP w rg o o E3 H E-t ORIGINAL CD < < O NUMBER CO M OF O iJ Q MICE FINAL EFFEC- TIVE NUMBER OF MICE ICA L D A MAXIMUM INCIDENCE OF TUMORS J. I. /weeks) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 103 C3H 3 100 20 17 9lt/23 1+.2!| RELATIVE CARCINOGENIC POTENCY, pMC n -i4*01 0,lb-.03 l+l C3H 2 100 20 13 85/25 20.i l l 0 .1 6 _ * q | 19 CFW 3 100 20 11 100/37 2712 ^o.03!;oi 58 CFW 3 100 30 21+ 88/31 18.5*i 76 CFW 3 100 29 28 96/52 21.si? ^ 0.05^*02 13* CFW 3 100 30 16 13 CFW 2 100 30 28 91+/38 86A1+ 21+-3!| 23.8*JZ in ni +02 ^ 0 -0l4--.01 - 37 CFW 3 100 20 12 92A6 26-5 ~ o . 3: :j; 37 CFW 3 100 10 5 100/30 19.5!i 69 CFW 3 100 20 18 78/30 1+9 C3H 1 100 20 19 siiAi 31+.1+!i ^ 0.13i .01 77 CFW 3 100 20 19 89A 1 28^2 ^0.03i.01 API 05440 t f - 11 - TABLE I SKIN PAINTING EXPERIMENTS 01' HIGH BOILING SAMPT.ttfl A H A L Y T I CAL D A T A -- ^ PROCESS T. C. C. n it * API SAMPLE NUMBER PRODUCT 3 Cracked sidestream 60 Cracked sidestream 109 Cracked sidestream 7 Cracked residuum 9 Cracked residuum DISTILLATION (2mm. corr to 760*. GRAV ITY VISCOSITY <750 9725500 >925 E.P. (*) (%) (*) (*F.) 33.2 32.7/ 100 SSU 214..9 0 00 100 2J+.1 20.2 46.1 /100 SSU 34.5/ 100 v l O O SSU 18.4 97 2.33 780 10 Cracked 1 1.6 117 /100 56.7 36.6 6.7 - residuum SSU 31 Cracked 16.0 14 .8/122 35.6 870 residuum SSP 36 Cracked . 21.9 90/100 48 892 residuum SSU * 40 Cracked 19.8 residuum 77.2 22.2 .65 860 71 Cracked 22.8 59/100 77 21.5 1.5 845 residuum SSU 78 Cracked 16.1 residuum 45.7 44.' 10 - n 82 Cracked 13.6 126/130 25.7 51.5 22.8 - residuum SSU API 05441 * - 11 - table i -- API sample jtJMBER SKIN STRAIN OP MICE AND NUMBER OP APPLICA TIONS PER WEEK DOSAGE PER AP PLICATION (mg.) PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES B I C L 0 G ICAL DATA ORIGINAL NUMBER OP MICE PINAL EFFEC TIVE NUMBER OP MICE MAXIMUM INCIDENCE OP TUMORS 1.1./weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, ?MC 3 C3H 1 100 20 9a 0/62 - - 60 CPW 3 100 20 109 C3H 3 100 20 7 C3H 1 100 20 9* C3H 3 100 10 9# CPW 3 100 20 10# C3H 1 100 20 31 C3H 1 100 20 A 57A 8 15 93/25* 9X 11/55 9 100/1+7 16 oo/i+i 17 91+/39 17 100/32 37.SIJ r J 0,01 ,1 16.72 r\ it A-.02 - - 33.8$ 27. 8 $ / V 0.05-.01 a J 0.03 .01 22.51 \ .26!;3| 1 19.3 0.391;^ 36 C3H 1 100 20 16 9fcA4 31.3f ^ o.i5: 1+0 C3H 1 100 20 71 C3H 1 100 20 9 100/1+2 20 90/22 32.23 is! A'O.ll^ o.sa:2I 78 C3H 1 100 19 17 82/20 82 C3H 1 100 20 20 95/31+ 11+.81 26 0.59.01+ in o / V o o+ 25 *2-.02 4 < * Number alive after 52 weeks. 8 Crusts, comparable to those p r o d u c e d by dodecylbenzene, developed In the early stages of the test on API-109 and were sloughed after II 7 -10 weeks. c 0 - i:-. - TABLE I SKIN PAINTING EXPERIMENTS OK HIGH BOILING SAMPLES A N A L Y T I CAL D A f j| -*1 PROCESS API SAMPLE NUMBER PRODUCT GRAV ITY DISTILLATION | 2mm sorr. to 760nmm VISCOSITY <750* (%) 750 925 >925* E.PJ (%) <*) !P.) c c N k Cracked sidestream 23 Cracked sidestream 21.6 26.7 55.5/100* 78.5 20.6 .9 838 ssu 1* Cracked sidestream 87.9 12 .1 0 780 ff 88 CrAcked 22.5 78/100 69.3 30.2 .5 900 sidestream SSU ff 89 Cracked 27.0 51/100 100 7k$ sidestream SSU 91 Cracked 20.k 57.8/100 80.1 17.9 2.0 830 sidestream SSU m 101 Cracked 2I4..8 14.0.1 /100 89.7 9.1 .3 790 sidestream ssu * 102 Craoked 23.5 53.1/100 99 - 1 750 sidestream ssu ti IOI4. Craoked 7.6 sidestream API 05443 TABLE I --- API SAMPLE DUMBER SKIN PAINTING EXPERI.4ENTS ON HIGH BOILING SAMPLES STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK B C0I 0 G I C A L DATA i - JP M g Et] E-* ORIGINAL O < NUMBER < o cn m . OF O Q 4 . MICE FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T.I./weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC C3H 1 100 20 91 0/69 mm - 23* CFW 3 100 20 23* C3H 2 100 20 1+6* CFW 3 100 20 88 C3H 2 100 20 20 100/19 18 91+/28 15 100/21+ 18 9lt/26 10+3 1 7 .2+2 "3 15.2 3 ^.i-:Sf / V 0.20+.01 89 C3H 3 100 30 28 89/21 12+1 - 91* C3H 2 100 20 19 9 k /2 3 16+1 /^o.i9i.oi 1018 C3H 3 100 20 6 100/12 7 - 102 C3H 2 20 20 20 0/3 - 102 C3H 2 100 20 20 0/3 - 101+ C3H 3 100 20 5 100/12 7 101+ C3H 2 100 20 20 0/3 - 101+ C3H 2 20 20 20 0/3 - mm mm ID O M < 1 Number alive after 2 weeks. 8 Crusts, comparable to those produced by dodecylbenzene, developed in the early stages of the test on API-101 and were sloughed after 5 to 6 weeks. V - JO - TAi'-E I SKIN PAINTING EXPERIMENT! ON HIGH BOILING SAMPLES API 05445 * - 13 - 1V3LE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES STRAIN OF MICE AND NUM3ER OF API APPLICA SAMPLE TIONS number PER WEEK i '7 B I O L 0 G I C A L DA ? ce KJ a: a. O M M Eh ORIGINAL C < < O NUMBER CO M O J OF Q eh MICE FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMCRS tf.I./week) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC 8* C3H 3 100 30 23 91/16 7 . 6^ 8 C3H 2 100 20 17 9ll/lil 5 . 7^ - 8* C3H 1 100 20 17 9 k/k 4.-U-I1 0 61+*0^ u* -.09 8 C3H 1 20 20 19 1 0 0 / 5 0 33.7 n / 0u ,1i-3J-+..0037 8 C3H 1 5 ko ko 0/3 - - 8 C3H 1 20 ko ko 0/3 tm - 8 C3H 1 50 ko ko 3-U. C3H 3 100 30 21 0/3 86/23 16.6*^ - n . 1 + .0 1 Ooll4- . 0 2 8-16 C3H 1 100 20 3-21 C3H 1 100 20 19 100/52 n .z t k ^ 0 . 1 5 ! ; o3 17 70/27 2 0 . 2 ^ 12 CF71 1 100 18 17 88/3U 111. 7 12 CFW 3 1 0 0 15 Ik 100/34 8- f 26 C3H 1 100 20 19 100/20 1*3 o.72*;|j kz C3H 1 100 20 18 9ll/3ll 2 2 .iil o .2 7 i;g1 4-3 C3H 1 100 20 15 IOO/ 3 7 33.113 /VO.H4.+ .02 API 05446 TABLE I S K IN P A IN T IN G E X P E R IM E N T S 01* H IG H B O IL IN G SAM PLES A N A L Y T I CAL D} TA PROCESS F. C. C. ! n API SAMPLE NUMBER PRODUCT 1+1+ Cracked residuum 1+8 Cracked residuum 68 Cracked residuum 73 Cracked residuum 85 Cracked residuum DISTILLATION |2mm cjorr. t0 7603m} GRAV ITY 15.2 6.0 VISCOSITY 214.1 / 100 SSU <750 (0 31.1 750 925 >925 E.P. (*) (*) P.) "" 51+.2 13.6 - 9 1 .7/100 1+7.1 37.3 15. b - SSU 9.8 81/130 1+3.3 1+1+9 11.8 SSU f 17.5 16.9/122 21 62 17 SSF 8.1 216/100 1+2.6 1+7.8 9.6 ! SSU API 05447 T Hi. - A 1V3LE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES -- 3 10 L 0 G I C A L DA T A API SAMPLE DUMBER STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK < "3 e- c M M &H O R I G I N A L < O < U NUMBER GOl MJ OF Q ~ MICE FlNxiL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T. Io/weeks' AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (w e e k s ) m C3H 1 100 20 16 91+AO 271] RELATIVE CARCINOGENIC POTENCY, pMC C3H 1 100 19 13 100/36 3 0 . 1 ^ a ^O, 1 6 _ 'Q 2 68 C3H 1 100 20 15 100/ 1? 13.5: l o . 65 : :i 73 C3H 1 100 20 12 73 C3H 1 100 20 20 83/22 95/31 18^ 22.5^2 Oe~-o07 35 C3H 1 100 20 18 100/25 <1 o.sai;:!! API 05448 TA3LE I SKIN PAINTING EXPERIMENTS 01 HIGH 30ILING SAMPLES A N A L Y T I C A 4- J fi PROCESS Houdry n n API SAMPLE NUMBER PRODUCT 11 Cracked residuum 3k Cracked residuum 50 Cracked residuum 51 Cracked residuum 63 Cracked residuum DISTILLATION (2mm corr BU0 C"******"*,V1j 750. GRAV <750' 925c>925' i ITY VISCOSITY (*) (%) (*) if.3 71/100 81+ lo 0 -* 1 220 S3U 28.0 1+7.5/100 SSU 9 -j r> 21.3 6i+/l00 85 15 0 " 20 ! i SSU 25.7 67/100 83 17 0 811 SSU 2 5 .6 25.7/100 SSU 1+8.5 37.6 1 3 .9 H 81 Cracked 22.7 1+0/210 1+0.8 5 2 .6 606 - residuum SSU Cycloversion 22 Cracked residuum 25.6 1+9.5 1+1+2 6 .3 - 1 k API 05449 J : T. 3LE I ^ SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES --- 3 T 7 T T 7 T T T (i A L D A f A " API sample jiUMBER STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK < % M ORIGINAL ClI E-! O < NUMBER < U CO M OF C ' MICE Q c- FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T. I./weeks' AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC 11 C3H 3 100 20 19 89/19 13.5l| /v 0.17i.03 CFW 3 100 18 17 9 k /}2 19.5!? 0.061.01 50 CFW 3 100 20 16 100/21 1 3 .0 : 1 -S 0.11i.02 51 CFW 3 100 20 63* C3H 3 100 20 63 C3H 3 100 19 63 C3H 2 100 20 o3 C3H 1 100 20 31 C3H 1 100 20 31 C3H 1 100 llO 31 C3H 1 20 llO 18 83/19 18 89/26 15 100/19 13 100/33 19 37/36 20 IOO/ 3 6 1^0 0/3 ko o/3 12.6+J - 19!f I5.iii 21.5^ 26.3^| - -i 2::o 2 O.1 5 + 0CI ^-i5i:o2 - ^ o .2o !;| - 22 CFW 3 100 20 15 93/17 io !? - API 05450 TABLE . S K IN P A IN T IN G E X P E R IM E N T S ON H IG H B O IL IN G SAM PLES A NALY TICAL D"T T a **ISTILLATICN (2mm corr.to 760a^ PROCESS API SAMPLE NUMBER 750 GRAV <750 925 >925 PRODUCT ITY VISCOSITY (*) (*) (*) (%) Solvent extraction Ik Furfural ex 10.3 1910/100 3 0 .: b9.7 - 902 tract from ssu Kansas 200 stock It 15 Furfural ex 10.9 1 ^ 303/ 10 0 'll*.7 85.3 tract from ssu Oklahoma 1*00 Pale 16 Phenol extract 9.7 352/210 62 910 from Coastal ssu 900-X M 17 Duosol extract 7.1 2276/210 3 23.7 68.3 from Califor ssu nia waxy ' residuum, $0% in sec.-amyl benzene ft 27 Phenol extract 11.0 173/100 19 910 from San ssu Joaquin naphthenic distillate t! 70 Nitro-benzene 15.7 99.1*/210 5 85.3 11*.2 extract from ssu Barbers Hill 60/30 II 75 S0a extract ll+.i* 38,3/100 100 from TCC ssu gas oil API 05451 lo r. ISLE I SKIN PAINTING EXPERIMEI.TS ON HIGH BOILING SAMPLES --- API sample vtjMBER -- STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK Ik CFW 3 1 ft* I n-> a cu 03 M M Eh g < < O w m 0 a Q -- BIO ORIGINAL NUMBER OF MICE L C G I C A L DA FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T. I./veeks) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 100 20 9 33/11; - RELATIVE CARCINOGENIC POTENCY, pMC - 15 CFW 3 100 30 0^ 0/1k - - 16 CFW 3 100 10 6 16 C3H 3 100 10 7 17 CFW 3 100 20 12 67/73 13/70 67/62 25^2 s U 0 .03 .0 1 % 27 CFW 3 100 20 12 83/17 0 .13 + .0 3 70 CFW 3 100 20 6 70 C3H 3 100 20 lk 75 CFW 3 100 20 13 50/25 93M 77/51 22. 3t.8| ^ 0 .05!;! ^o.o5;gf 29 4 ! i r J 0.021.01 ~ All animals dead in 1k weeks. API 05452 - 17 - TABLE I SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES ANALY TICAL D A?r PROCESS API SAMPLE NUMBER SPECTRUM TYPE1 OR PRODUCT GRAV ITY DISTILLATION (2mm corr. to 7>0bb^ VISCOSITY 750 C750` 925 >925 E.. (*) (*) (*) P.) Straight run 1 Distillate 31.9 37/100 I distillation # 11896 SSU \ n 56 Waxy Midcon 29.9 87/100 5 2 .I1 1+1.6 (2.0) 330 tinent dis SSU tillate, ! Type B (.5) t I ft 79 San Joaquin 16.6 63.9/210 a /13 86.2 855 I naphthenic SSU i distillate, Type C (2.2) I 105 West Texas 28.9 51;.3/100 72.c 23-4 33 m paraffin SSU distillate, Type B (.5) Hi; Type B (.6 3 ) 21;.6 235/100 SSU t 115 Type C (.58) 2 3 .2 231;/100 SSU tt ' 5 Residuum from 12.8 572/12: 26 26 w - Wilmington SSF crude #11885 Distillation 25 700+ bottoms 21;.3 1 1 5 /10 0 1;9 k S 6 from F.C.C. SSU heavy cycle gas oil Dilution of No. 25 25-1 $ 0 % oil No.25; 50# (White oil + W. Texas residuum) l See page 8 of Section A of report of the classification of Straight dated April 5 Run Distillates 1952, for discuss!:by Spectrum Type API 05453 - 17 - 'ABLE I SKIN PAINTING EXPERIME ITS ON HIGH 30ILING SAMPLES r--- API sample number STRAIN OF MICE AND NUMBER OF APPLICA- TICNS PER 77EEK -- 3 10 0-, A <* g IX Cd 3 CL, O M Cd Si ORIGINAL o < J o NUMBER CA M O `- OF Q =- MICE L G 1 C A L DA FI. AL EFFEC- TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T.I./weeks) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, ?MC 1 C3H 1 100 20 21 0/72 - - 56 CFW 6 100 20 16 * 56 CFW 3 100 20 17 81/22 88/22 l^-7!j - 0.09.01 79 C3H 2 100 20 100/33 m 79 C3H 2 100 20 15 67/57 3o.ai| /O c 3 * > 0 .3 6 1.0 2 105 C3H 3 100 20 17 38/33 21.2^ CVjr^ O O . -4- 1 i-- 1 O 111; 115 5 C3H 1 100 20 21 0/"6 - - 25 C3H 3 100 30 22 82/19 12.5! 1 - 25-1 C3H 3 100 30 26 I Number alive after 52 weeks 92/1+0 23^ o.o9+;8f API 05454 - 1'. TABLE SKIN PAINTING EXPERIMENTS ON HIGH BOILING SAMPLES ;l N A L Y T I C A L T. A T PROCESS API SAMPLE NUMBER SPECTRUM TYPE1 OR PRODUCT GRAV ITY DISTILLATION (2mm corr. to 760sr^ VISCOSITY <.750 (*) 750 925 >925 S.p. (%) (%) (p.) Fractional 110 -1 Type B (OO4.) 61.0 .95/70Fa 100 distillation i ft 1 1 1 -lj. Type 3 (1.62) 23.0 17/llj.OFa Dilution of No. 111-lj. 111-6 50% No. 110-1 $0% No. III-I4. tt 111-7 50% No. III-I4. ? 50% No. 112-1 Fractional 112 -1 Type 3 (.016) 65.9 dis tillation i j w 112-3 Type B (.01+5) 39.7 i l Lubricating oil 99 Type C (.5) 20.0 52/210 ^v/38 SSU tt 100 Type B (.3) 29.5 53/210 SSU Wax pressing 32 Dewaxed paraf fin distillt fraction from Lima crude ff 57 Dewaxed oil 28.7 9 1 .3/100 80 19.5 .5 898 from No. 56 SSU MEK - 3enzol 14.3-1 Dewaxed oil 12.9 195/100 29.5 57 13.5 solvent from F.C.C. SSU dewaxing decanted oil No. I4.3 1 1 See page 8 of Section A of report dated April 5 1952 for discussion of the classification of Straight rtun Distillates by spectrum type. 3 Kinematic viscosity (centistokes). API 05455 - 13 - Tl 3LE I SKIN PAINTING EXPERIMEN S CN HIGH SOILING SAMPLES API sample vrrMBER STRAIN OF MICE AND NUMBER OF APPLICA TIONS PER WEEK 3 I 0 L 0 1 C A L DA l < s' rr 3 3 <O--t y 3 H < ORIGINAL < O NUMBER CO M O J OF Q ^ MICE FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS JT I./weeks ) T A AVERAGE LATENT PERIOD FOR TUMOR INDUCTION ' (weeks) RELATIVE CARCINOGENIC POTENCY, ?MC 110-1 C3H 3 2C 20 20 0/22 - - 111-14- C3H 3 20 19 17 83/22 1 6 .61 0.114.1.0 1 111-6 C3H 3 20 20 20 20/22 - - 111-7 C3H 3 20 20 20 30/22 - - J 112-1 C3H 3 20 20 20 0/22 - - 112-3 C3H 3 20 20 20 10/20 - - 99 C3H 3 100 20 16 100 C3H 3 100 20 18 9-^7 o/h.9 23.5114- 0.07.02 - 32 CFW 100 20 15 ,A- / 30.8^| - (3-6)1 SI* CFW 6 100 20 17 100/25 -i - 4-3-1 C3H 1 10C 20 19 914-/25 19 2^1 0.ii-0+o<?? -lo week thereafter, API 05456 TABLE I SK IN PAIN TIN G EXPERIM ENTS 0 / H IG H .B O ILIN G SAMPLES A NALY TICAL D *T A API SAMPLE TOMBER PRODUCT GRAV ITY DISTILLATION | (2mm corr. t0 760tnmJ VISCOSITY <750 00 750 925e >925 (*) (#) H.P. p A Filtration 8-3 dewaxing of No. 8 Desulfuriza 21 tion of 8-3 [hydrogenation Acid treating 62 Effect of viscosity on tumor induction !! Ilk 111+-1 Fuel oil 113 blending Press oil, 85# of origins: (.91+# s ) Hydrogenated heavy gas oil M 5 * s) Hydrolyzed acid sludge Straight run distillate, see page 17. of Appendix 95# API-111+, 5# alkylpoly- styrene Industrial fuel oil 11.3 18.1 21+.6 235/100 SSU 1756/ 100 SSU 30/ 122 SSF 65 21.1+ 13.1+ - 71+ 20 58 6 ' 850 r k3> 20 37 _______________ 1 API 05457 T - 19 - 1 13LE I i SKIN PAINTING EXPERIMENTS ON HIGH SOILING SAMPLES -- 3 10 L 0 G I c a l n T I STRAIN 1 - OF MICE < S API SAMPLE number AND NUMBER OF APPLICA- TIONS PER WEEK a s_ 3. O Cd M =-t ORIGINAL 0 < NUMBER < CO M OF 0 j MICE .Q Pi FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS J.I./weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC 8-3 C3H 3 100 20 20 90/17 . 1+ HU> ni 21 C3H 3 100 20 20 100/13 8 -2! - 62 C3H 3 100 20 17 214./79 - - m 1111.-1 1131 C3H 3 20 27 23 1*8/20 1132 C3H 3 20 27 l6 1138 C3H 3 20 27 25 69/20 6Q/- ' 1133 C3H 2 20 27 23 13/19 1133 C3H 1 20 27 27 0/20 1133 C3H 3 100 14-0 37 73/20 1133 C3H 3 5 39 38 71+/20 1133 C3H 3 1 20 20 0/3 113? C3H 3 20 20 20 /3 _ 1 1 C3H 3 20 20 20 o/3 2 Age of mice at start of experiment, 17 weeks. 3 Age of mice at start of experiment, ll^. weeks, ^ Are of mice at start of experiment. 8 weeks. - 17.211 17.21 -- - - - - 0.131.01 0.131.01 * -- API 05458 \ - :0 - TABLE I SKIN PAINTING EXPERIMENTS 0' HIGH BOILING SAMPLES PROCESS API SAMPLE NUMBER PRODUCT Fractional distillation of No. 8 H ft H CO 1 CO 8-61 b. 35-83C./0.01+ mm.; 0-9.3# 8-71 b. 83-102C./0.02 mm.; 9.3-19.1+# b. 102-133C./0.03 mm.; 19 .I+-3O.3# Tt 8-91 b. 133-139C./0.03 mm.; 30.3-39.8# 8-101 b. 11+2-175c /0.03 mm.; 39.8-1+9.6# tt 8-1 1 1 b. 175-197C./0.03 mm.; 1+9.6-59.2# Tt Diels-Alder reaction 8-12 1 b. 198-217C./0.035 mm.; 59.2-69.1# 8-12a l non-adduct from reaction (951+# of API-8-12) Fractional distillation of No. 8 ft 8-131 b. 2l5-238C./O.Oi+5 mm.; 69.1-78.5# 8-1I4.3 b. 238-258C./0.0l+5 mm.; 78.5-80.8# m Diels-Alder reaction 3-151 Residue; 80.8-100# 8-18 Reblend of distillation fr-" -ions, 3-6 thru 8-15 8-23a- Materials extracted from API-8 by maleic anhydride 8-23h Solvent extraction with corn. H aS04 8-191 Extract from 8-10 and 8-11 8-201 Raffinate from 8-10 and 8-11 It 23-1 Extract from No. 23, 20# in benzene tt 23-2 Raffinate from No. 23, 20# in benzene * .Fractionation 12-73 Non-adduct of Diels-Alder reaction on raffinate _______________ from sulfuric extraction of fraction b.l30-l80C/.- 1 50# solution in benzene. 2 333/0 Solution in benzene. 3 30# solution in benzene. API 05459 r--- API SAMPLE DUMBER S K IN P A IN T IN G E X P E R IM E N T S ON H IG H S O IL IN G SA M PLES STRAIN OF MICE AND NUMBER 0F APPLICA- TIONS PER WEEK 3 10 L 0 G 3 : C A L DA T A r** 5 s e- o a s* ORIGINAL o < < o NUMBER CO M OF O 1-3 Q C-. MICE FINA. EFFEC- TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS [T. I./weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC 3-6 C3H 2 100 20 121 0/66 - - 3-7 C3H 2 100 20 121 3-3 C3H 2 100 20 161 9-9 C3H 2 100 20 18 8-10* C3H 2 100 20 16 8-11* C3H 2 100 20 20 8-12* C3H 2 100 20 14 8-12a* C3H 2 100 16 16 3-13* C3H 2 100 20 14 3-16. C3H 2 100 20 12 8-15 C3K 2 100 20 13 3-18 C3H 1 100 15 14 3-23a- C3H 3 15 20 20 3-23h 3-19 C3H 2 100 9 9 C3H 2 100 9 9 23-1* C3H 2 100 20 19 23-2 C3H 2 100 20 19 12-7 C3H 2 20 20 1 Number alive after 52 weeks. 0/74 0/74 55/62 94/44 90/33 93/28 100/26 79/25 25/21 92/35 9*/*' 0/3 22/32 67/28 89/26 100/44 - 32!f6 291 { 23.5 18+2 16-1 20.5!? - r J 0.09 /v 0.14.01 0.14+.01 /V 0.184.02 A* 0.19i.01 A* 0.164.01 - 26.6-2 1 2 .7!-j; - - ^ 0.124.01 - - 22.6+2 16.342 2! ^ - /v o.iSi;gf V 0.19!*0k o.i3i:8i API 05460 o i ro C D CO TABLE I SK IN PA IN TIN G EXPERIM ENTS 0. HIGH B O ILIN G SAM PLES PROCESS API SAMPLE NUMBER PRODUCT Air oxidation 83 Two hour oxidation product (cobalt naphthenate catalyst) n 83-1 Four hour oxidation product _ 83-2 Aromatics by chromatography from No. 83 plus 30.6# by weight of sec.-amylbenzene Chromatographs 8-22 8-5 Aromatics by chromatography from API-8 plus 30.6# by weight of sec.-amylbenzene Aromatics of No. 8 from Silica Gel m 8-17 Reblend of chromatography fractions of No. 8 n 12-2 Non-aromatics (cut with 20# heptane) Distillation '1 plate vacuum) n n 12-ij. Aromatics b. 510-710F. (corrected) 12-5 12-6 Aromatics b. 1010-1065F. (5 g./l00 ml. benzene) Aromatics residue; b.^1065''-^. (5g./l00 ml. benzene Chromatography 71-1 See page 3ii of Section A-I4. of report dated April 5 1952, for description 99 71-2 Proportionate reblend of all fractions from chromatography of API-71 71 See page 11 of Appendix for description API 05461 ) 1 - 21 - TABLE I SKIN STRAIN OF MICE AND NUMBER OF API APPLICA SAMPLE TIONS NUM3EF PER WEEK P A I N T I N G E X P ERIN. :NTS O N H I G H B O I L I N G S A M P L E S 3 I o~T F T T 0 A L D T T I ------- < i *>- a a a o t-- 1 a Eh 0RIGINAI o c C O NUMBER CO M OF o a O Ch MICE FINi L EFFEC TIVE MAXIMUM NUM3ER INCIDENCE OF OF TUMORS MICE T.I./weeks' AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) RELATIVE CARCINOGENIC POTENCY, PMC 33 C3H 2 100 20 Ik 100/17 1 1 .6^ - 33-1 C3H 2 100 20 16 91+/17 33-2 C3H 1 100 20 19 1+7/37 8-22 C3H 1 100 20 19 14-7/36 1 C1D vn C3H 1 100 20 i co CFW 1 100 20 8-17 C3H 1 100 20 12-2 CFW 3 100 20 1 12-1+ CFW 3 100 20 12-0 CFW 3 100 20 12-6 CFW 3 100 20 71-1 C3H 1 20 30 12 92/22 19 71+/28 17 91+/30 IS1 o/i+ia 16 56/3U 12 92/31+ 12 b7/8" 30 3/9 71-2 C3H 1 20 30 30 i 0/20 71 C3H 1 20 33 33 15/19 i 1 Number alive after 3 weeks. E x p e r i m e n t d i s c o n t i n u e d a f t e r 1+1 w e e k s . nil - - - - - 17!i 10.!+:J;2 139it - o.5::8^ - -637.27 - *1 003_ #oi+ / J 0.0J+.02 - - - - - - - API 05462 ) ) ) TABLE II CONCENTRATION STANDARDS WITH METHYLCHOLANTHRENE IN BENZENE API SAMPLE NUMBER NUMBER ORIGINAL OF NUMBER C0NCEN- APPLICA OF T R A T ION TIONS1 MICE (gy^lOO ml.)['ER WEEK C3H CFW FINAL EFFECTIVE NUMBER OF MICE C3H CFW MAXIMUM INCIDENCE OF TUMORS (T .1./weeks) C3H CFW AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) c 311 CFW STARTING DATE 220 0 3 20 20 lO3 133 0/90 0/62 - - 12/4/50 201 0.01 3 10 10 9 1*4/71 100/70 - - 7/20/1,9 210 0.02 3 20 lip 78/53 30.5^ 2/3/50 203 0.075 3 10 10 9 9 100/34 100/23 24.5-2 ilif 5', -0/49 203 0.075 3 20 10 20 7 85/35 100/31 28.7!^ 20.92 10/9/50 219 0.10 3 30 20 20 l6 9^/35 100/33 21.8l| 1 4/14/So 2l|.3* 2if32 o.i3 o.i3 3 20 3 20 20 100/24 19 100/26 17.5*1 1 7 .6*3 7/28/51 10/1/51 221* 205 2092 0.10 0.30 o.45 1 20 15 87/49 W-U 8/ 22/50 l 20-:: 20 19 17 100/35 100/30 2 \ t [ 22 .J|3 6/ 13/50 1 20 20 100/24 17.8-1 10/4/51 1 Dosage per application was 100 mg. except where otherwise specified, p Dosage per application was 20 mg. 3 Number alive after 2 week3. API 05463 TABLE II CONCENTRATION STANDARDS WITH METHLCHOLANT1IHENE IN BENZENE API SAMPLE NUMBER C0NCEN- T R A T ION (g./l00 ml. NUMBER OP APPLICA- TIONS1 PER WEEK ORIGINAL NUMBER OF MICE C3H CFW PINAL EFFECTIVE NUMBER OF MICE C3U CFW MAXIMUM INCIDENCE OF TUMORS ( T .I . / w e e k s ) C3H CFW AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) C.3II CFW 2 0 6 -::220 o.6o 0.90 1 20 1 20 20 IOO/3O 20 IOO/1 8 *5-1 7.2 230 232 205 0.20 0 .2 0 0 .3 0 2 20 2 20 20 95/22 20 1 0 0 /2 7 15-i 1 7 .1^ 2 20 20 20 l6 100/20 88/25 l3.7f 15.2^ STARTIuG DATE 10/ 10/50 5/3/50 10/2/51 6/9/50 API 05464 Dosage per application was 100 mg. except where otherwise specified. Dosage per application was 20 mg. T Aliali 11 CONCENTRATION STANDARDS WITH SYNTHETIC CARCINOGENS1 IN DODECYLBENZEUE2 API SAMPLE NUMBER C0NCEN- TRA T ION g /100 ml. NUMBER op APPLICA- T I O N 3 -5 PER WEEK ORIGINAL NUMBER OF MICE C3H CPW PINAL EFFECTIVE NUMBER OF MICE C3H CFW MAXIMUM INCIDERCI I OF TUMORS ( T .I . / w e e k s ) C3H CFW AVERAGE LA']'ENT P E R I O D FOR TUMOR INDUCTION (weeks) C3H CFW RELATIVE CARCINOGENIC POTENCY, Pm c C3H CFW 2 2 1 -::2 2 1 - 1^*' 221- ^ 226 225-::- 213 211 200 2l|9^ A9 212 0 0 0 0.005 0 .0 1 O.Olp 0 .1 0 0.13 0.15 0.15 0 .3 0 3 20 1 33/37 -- 3 3 3 0/3 - - 3 3 3 0/3 - - 3 20 20 11 17 SSAo iii/A - - - - 3 20 20 l6 11 01A 3 91/ A 3l*^Jo 3 20 15 100/18 10 ^.02J01 lo - 3 20 6 20 7 100/22 10 0 /17 i o .5 ! f 9 . S ! ]{ - - 3 30 30 100/15 9.S U - 3 20 18 09/A .i^ ~ 3 20 16 100/12 8 .0 1 - 3 20 19 100/ 1 9.51 - 21*51 o .i5 3 20 1 100/19 9.7J - API 05465 * * v w * * * v j - * * *- ' v**j w j -------- i ----- - -- ---- r * ' f ----- ----- -- ' * * P 3 ,ii-benzpyrene was used. Proauct obtained by alkylation of benzene with the propylene tetramer (aluminum chloride 3 Dosage per application was 100 mg. except where otherwise notod. catalyst) `i D o s a g e p e r a p p l i c a t i o n w a s 2 0 m g . / ll-ii2# f r a c t i o n o b t a i n e d f r o m A P I - 2 2 1 b y c h r o m a t o g r a p h y f r o m a l u m i n a , o l|2-0l|./lS f r a c t i o n o b t a i n e d f r o m A P I - 2 2 1 by c h r o m a t o g r a p h y f r o m a l u m i n a . ) ) ) TABLE II CONCENTRATION STANDARDS WITH METllYLCHOLANTHRENE IN S E C .-AMYLBENZENE API SAMPLE NUMBER NUMBER OP CONCEN- APPLICA.- TRATION TIONS1 (g./l0 0 iiil. :PER W E E K ORIGINAL NUMBER OF MICE C3H CPW PINAL EFFECTIVE NUMBER OF MICE C 3 II C F W MAXIMUM INCIDENCE OP TUMORS ( T .I . / w e e k s ) C3H CFW AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) C3H CFW RELATIVE CARCINOGENIC POTENCY, C3H CFW 22I4. 0 3 30 23 17/59 - - 223 0.075 3 20 20 l6 18 8 1/ 1^6 8 3/ 1*6 3 2 9 .2 +^ ^-.OE *>D2.01 222 O.I5 3 20 20 20 19 lOO/l^i. I O O / 3 3 2 t)-.5 f 2 2 .6 2 .0 8 .01 /^.Q5.0 1 23k O.3O 2 20 19 100/27 1 5 .1 '- <-- 235 O .60 2 19 19 IOO/I9 12.8 D o s a g e pe* a p p l i c a t i o n w a s 100 m g . API 05466 T A B L E II C O N C ENTRAI'ION S T A N D A R D S W I T H S Y N T H E T I C C A R C I N O G E N S IN V A R I O U S S O L V E N T S API STARTAMPLE INO IUMBEH DATE FARCIN- 00 E N 1 SOLVENT CONCEN- STRAIN TRATION OP g/l.OOmL.) M I C E 2/17A 7 MC 218 2/3/50 MC 218 2/3/50 MC 2l,l* 9/ll|/5l BP A n - 8o2 Sat.Sol. C3H (^0.2 g.) API-53 0.30 CPW AP 1-5 0 .3 0 C3H benzene 0.15 C3H 2lt5 12/3/51 BP DDB 0.15 C3H 2 l ^ 3/22/52 MC \PI-112-:i 0 . 1 5 C3H 2k61' i i / n / 5 2 M C IPI-113-J o . i 5 C3H 2k7 W 5 2 MC API-80 0.20 C3H 2l|8^ i^/n/52 MC iPI-110-1 * o .i5 C3H NUMBER OP ORIGINAL APPLICA- NUMBER TIONS OP PER WEEK MICE FINAL EPPEC- TIVE NUMBER OP MICE MAXIMUM INCIDENCE OP TUMORS (T.I ./weeks) 1 20 l6 01A9 3 20 16 81/29 3 20 17 100/30 3 20 20 100/33 3 20 18 IOO/19 3 20 20 100/22 3 20 18 9ll/l9 3 7 7 86/20 3 20 20 75/19 AVERAGE LATENT PERIOD /OR TUMOR INDUCTION (weeks) RELATIVE CARCIN OGENIC POTENCY, PMC 33.5 ^0.13 22 3.2!} 2l| .6!$ 9.7*3 12.6^ 15.3^ i6.ii *5 or* S ' " .02 - ^ - : 002 o.o01;O3 - o.i5:*.oi P 2 0 - M e t h y l c h o l a n t h r e n e ( M G ) and 3,lj-Bonzpyrene (BP) . ~ Technical white oil. 3 Wilmington residuum; see page 17 of Table I for description. R; D o s a g e p e r a p p l i c a t i o n w a s 2 0 mg. See page l8 of Table I for description. API 05467 TABLE II API SAMPLE NUMBER SOLVENT CONTROL EXPERIMENTS WITH VARIOUS SOLVENTS NUMBER OP APPLICA TIONS PER WEEK ORIG]:h a l NUML1ER OF1 MIC:e C3H CPW FI NAL EFI'E C T I V E HUM BER 0F MI CE C3U CFW M A X I M U M 11 C I D E N C E O F TUMCIRS ( t u m o r inc ex/weeks) C3H CFW INCID1ilNCE OF G1iOSS CARCINCIMA (//wee?ks) C3H CFW 80 White oil 3 95 White oil 3 221-::- Dodec y l - 3 benzene 22I4 Sec .-amyl- 3 benzene 220 Benzene 3 2\\1 D i s t i l l e d 3 water 30 2l|> 33 2k1 20 18 30 23 20 20 /") 17 181 131 231 81 0/55 33/37 0/90 0/^6 0/^6 17/59 0/62 0/56 0/55 0/52 0/90 0/56 0/56 O fr' , '/ ^ 0/62 0/56 STARTING DATE 0/7/51 7/20/51 5/5/50 7/li|/50 12/ 1^/50 7/28/51 Number alive after 52 weeks. API 05468 ) ) TABLE II ------------------------ i E X P E R I M E N T S EMPLOYING A L I M I T E D NU M B E R OF A P P L I C A T I O N S OF M E T H Y L C R O L A N T H R E N E (MC) IN BENZEilE API AMPLE UMBER CONCEN STRAIN TRATION OF (g./100ml J M ICE NUMBER rOTAL NUMBER OF OF APPLICA APPLICATIONS TIONS OF PER WEEK MC SOLUTION SOLVENT APPLIED FOLLOWING LAST MC APPLICATION NUMBER F APPLICA TIONS ORIGINAL PER WEEK NUMBER OF OF SOLVENT MICE FINAL EFFEC TIV E NUMBER OF MICE MAXIMUM INCIDENCE NF T U MORS (T.I./wks: AVERAGE IATENT PERIOD FOR TUMOR INDUCTION (w o e lcs) 230 0.20 C3H 2 230 0.20 C3H 1 205 0.30 C3H 1 2l1-2 0.5 C3H 3 2l|2 0.5 CFW 3 l6 Nil 11 Nil 11 Nil ^ Benzene 6 j <- s Sec.-amyl- 6 benzene Benzene 6 yr ' N^ ''Sec .-amyl- 6 benzene 20 20 35/21 - 20 20 O/3 3 - 20 20 100/32 - 10 9 l| il/V < - i 10 6 100/15 9.7ll 10 9 09A 7 10. 5 * ^ 10 10 100/32 io*!+ API 05469 EXPERIMENTS ON ACCELERATION OE CARCINOGENESIS NY SPECIFIC SOLVENTS1 API EXPERI MENT NUMBER DESCRI.PT10N OF EXPERIMENT MATERIALS APPLIE 0 TO MICE DURING FIRST SIX WEEKS OF EXPERIMENT SEVENTH WEEK TO E N D OF EXPERIMENT STRAIN OF MICE NUMBER OF ORIGINAL APPLICA NUMBER TIONS OF PER WEEK MICE FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS (T.I ./wks .) d AVERAGE LATENT PERIOD FOR TUMOR INDUCTION ( w e e k s )- 2 2 1 -:: 9-::9-::- 2 2 1 -9 -::221-9 501,-9 57- 221-57 200 221-200 DDB API-93 A P I -9 DDB DDB PDD A P I - 5 7 3 *^ DDB API-208^ DDB DDB A P I -9 API-9 API-9 A P I -9 API-9 API-57 API-57 API-200 API-200 C3II 3 CFW 3 C3H 3 C3H 3 C3H 3 C3H 3 CFW 6 CFW 6 C3H 3 C3 3 20 18 20 16 10 9 20 ; 20 20 15 20 17 20 17 20 10 30 30 20 20 33/37 looA i 100/ 1|7 100 93/22 911/26 100/25 100/15 100/15 100/ 1.1, - 2 7 .8 33.0^1 13 .2I2 12.0 w l? 5 !( 9-5^1 5.0 1 Dodecylbenzenes obtained by alkylation of benzene with 12-carbon olefins; DDD obtained with P propylene tetramer; 2-phenyldodecane (PDD) obtained with 1 -dodecene. c Time measured from date of initial paintiup; w i t h m a t erial labeled with API code number, r See Table I for description. H' Rair c l i p p e d . ^ See Table II for description. API 05470 4 ) TABLE III EXPERIMENTS ON ACCELERATION OP CARCINOGENESIS BY SPECIFIC SOLVENTS 1 API EXPERI MENT NUMBER DESCRIPTION OF EXP E R IMENT MATERIALS APPLIED TO M ICE DURING FIRST SINGLE p SIX WEEKS APPLICATION NINTH WEEK OF IN SEVENTH TO END OF EXPERIMENT WEEK EXPERIMENT STRAIN OF MICE NUMBER OF APPLICA TIONS PER WEEK ORIGINAL NUMBER OF MICE FINAL EFFEC TIVE NUMBER OF MICE MAXIMUM INCIDENCE OF T U M O R S -, T.i./wks.)^ AVERAGE LATENT PERIOD FOE* TUMOR INDUCTION (w e e k s )3 229 230 231 232 236 237 239 2I4O Nil Nil Nil Nil DDB DDB Nil Nil API-229^5 Nil C3H - API-229^ DDB C3H 3 a p i -8^6 Nil C3H - API-8^ DDB C3H 3 API-8 DDB C3H 3 API-229 DDB C3H 3 API-8r water C3H 3 c a p i -8' white oil, C3H 3 API-80 tfO l|0 12/13 1*0 37 92/31* US 387 0/63 hS 3k 56/?^ 31 28 28/30 I40 38 87/22 30 26 0/60 30 21 0/57 - 10 - - o - V,J 9-l| - Dodecylbenzenes obtained by alkylation of benzene with 12-carbon olefins; DOB obtained with P propylene tetramer; 2-phenyldodecane (PDD) obtained with 1-dodecene. Single application followed by two week interval before furtiior treatment of inice. r Time measured from date of single application of carcinogenic material involved in experiment. ^ Solution of 0.5 g. 9 10-d imethyl-l,2-benzanthracene in 100 ml. sec.-amylbenzene . 5 Hair clipped. 6 See Table I for description. 7 Number alive after 52 weeks. API 05471 TABLE IV EXPERIMENTS ON THE RETARDAT LOU OF TUMOR FORMATION BY WASHING - CFW MICE API JARCIN- EXPERI 0UEN1C MENT OIL NUMBER APPLIED NUMBER OF AP PLICA TIONS PER WEEK HAIR CLIPPED PERIOD OF EXPOSURE TO OIL BEFORE REMOVAL BY WASHING WASHING AGENT ORIGINAL NUMBER OF MICE FINAL EFFECTIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS [T .I ./weeks i AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 8 o2 1 300 8 1 301 8 1 302 8 1 no Control none 20 (no washing) no 10 min. soap 10 solution no 1 hour 11 10 no l| h o u r s n 10 Hi 8 6 /2 6 U -I i, 1 0 /8 1 " 1 51 Hl/3 6 - V S 6 /7 0 - 12 122 3 303 12 3 30li 12 3 Y' Control none 15 (no washing) yes 1 hour soap l solution yes 9 hours 11 15 111 10 0 /4 111 1 0 0 /l+0 25.6 11 100/21 154 N u m b e r a l i v e a f t e r 5>2 weeks . 2 see Table I for description. API 05472 TABLE IV EXPERIMENTS ON Till: RETARDATION OF TUMOR FORMATION BY WASHING - CFW MICE API EXPERI MENT NUMBER NUMBER C A R C I N OF OGENIC APPLICA OIL TIONS APPLIEI PER WEEK HAIR CLIPPED PERIOD OF EXPOSURE TO OIL BEFORE REMOVAL BY WASHING WASHING AGENT ORIGINAL NUMBER OF MICE FINAL EFFECTIVE NUMBER OF MICE MAXIMUM INCIDENCE OF T U M O R S T.l./weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (w e e k s ) 305 O2 306 8 307 8 300 8 3 yes 3 yes 3 yes 3 yes 20 min. detergent 20 solution 1 hour II 20 1 hour white oil- 20 detergent 1 20 min. white oil 20 III 93/51 39 .2 ^| 17 9lp/Ml 3 2 .l1!? 20 85/t > 15 100/52 2 8 .2*3 113 1132 3 > ' Control none 20 (no washing) 309 113 3 ye 3 1 hour detergent 20 solution 310 113 311 113 3 yes 3 yes l| hours n 20 I4. hours white o il- 20 detergent 18 8 9 / 2 5 e :? 16 30/67 - 13 5l|/57 12 83/52 1,2 .6^ White oil rinse followed by washing with detergent solution. 2 See Table I for description. API 05473 API EXPERI MENT NUMBER TABLE IV EXPERIMENTS ON THE RETARDATION OF TUMOR FORMATION BY WASHING - CFW MICE DESCRIPTION OF EXPERIMENT NUMBER OF APPLICA TIONS PER WEEK HAIR CLIPPED ORIGINAL NUMBER OF MICE FINAL EFFECTIVE NUMBER OF MICE MAXIMUM INCIDENCE OF TUMORS T .I ./w e e k s ) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (weeks) 312 Barrier cream applied 9:00 AM API-0 applied 11:00 AM Removal of oil by wu3hing with detergent solution 12:00 AM yes 20 10 70/l|5 30.5^; 313 Barrier cream applied API-0 applied API-0 applied Hemoval of oil by wushing with deterge solution 9:00 AM 11:00 AM 2:00 PM i+:30 PM yes 20 13 100/31 'a) i3 Ji*1 VaJ API 05474 L E G E N D F O R D A T A SHE: _ ;! CII I N D I V I D U A L E X P E R I M E N T S S 0.bols ^ used in connection with aver ace weicht curves: Time of d eath (from di ease) of t h tumor-free mouse. L. Time of death (from disease) of 6 t h tumor-bearing mouse, ^or 'V Time mouse killed. Mouse missing from cage. gross and microscopic pathology: 3 Time of appearance of first papilloma in l th mouse. W h e n this symbol is first u s e d for a g i v e n m o u s e after its death, the p r e s e n c e of n o n - i n v a d i n g c a r c i n o m a (i n t r a - e p i t h e l i a l ) or small areas of benign neoplasm was determinable only by histopathology. .Cj Time of appearance of p a p i l l o m a which regressed later or was not confirmed by histopathology. Time of appearance of gross changes indicative of m alignancy in tumor of i th mouse. Diagnosis confirmed except in cases w h e r e no tissue s e c t i o n available. W h e n this symbol is first used for a given mouse after its death, the invasive malignancy of the tumor was determinable only by histopathology. Gross diagnosis of malignancy of tumor not confirmed by histopathology. (] o r & N o t i s s u e s e c t i o n a v a i l a b l e for h i s t o p a t h o l o g y b e c a u s e of extensive post-mortem decomposition or cannibalism. Tumors not recorded during this week. Cumulative dose-response otherwise specified): curves (summation rf data from all cages unless -n--------------; E x p e r i m e n t a l c u r v e f o r b e n i g n p a p i l l o m a s . ------------ -- - Hypothetical curve for papillomas. This curve furnishes average latent period (time for 50 percent t u m o r index) f r o m w h i c h r e l a t i v e p o t e n c y , P^c* *-3 determined). ----- --------- Experimental curve for grossly malignant tumors. API 05475 API 05476 12 l6 20 2I4. 28 32 36 k T IM E A FTE R FIR S T PAINTING (WEEKS) I s s u e d 9 / 1 A>< J U M O R INDEX {%) - 09 - AVnV 01 Ot 0 o 96 7i i ? n o o M i ' i i " / ' ) jcM i ' / m `0!1i ") 1!.H !M I^:h i i,v. ,j i ! ^Ni ; ' '/)', m j / o .-i h)/,7 AVERAGE WEIGHT OF SURVIVORS (GRAMS) API 05478 TIM E AFTER FIRST PAINTING (W EEKS) Issued 9/ 3 / V * -^.lurLAITSUM FROM THE KSTTZRINjS LABORATORY _ API RESEARCH PROJECT ON CARCINOGENICITY EPIDEMIOLOGICAL ^STUDIES September 2hr , 1952 During the four months following the summation given at the April 1952 meeting in Cincinnati, 37 case reports have been received, making a total of 939 collected by the Registry since its inauguration in September 1950. The accompanying tabulations (Pages 3, Ij., and 5) have been corrected to include the additional material but, as vrill be noted, the pattern found earlier has not been changed materially. Much effort has been devoted to preparations for the correlation of the occupational histories and the kind and degree of petroleum exposure with other variables. All of the reports were carefully reviewed in great detail, with particular reference to the descriptive terms employed by the various medical directors to describe the occupations and petroleum contacts of the cases reported. Prom the findings of these studies, codes have been drawn up to be used in the tabulation of these two important variables. The proposed classifications can be found on pages 17 to 20. The numerical codes employed for the other items are given also for your information. A sample of the Key-sort card has been included likewise. It Is hoped that the medical directors will be guided by these classifications in filling out future reports. It will be helpful if any error, inconsistency or difficulty Is encountered In using the occupational or contact codes, to bring it to our attention so that corrections can be made as soon as possible. A revised r e c o r d form embodying the new classifications is planned for distribution In the near future. i API 05479 T 4 FIGURE 1 - 939* CASE REPORTS FROM 13 COMPANIES RECEIVED BY THE CENTRAL REGISTRY ACCORDING TO SEX, RACE AND MALIGNANCY SEX RACE MALIGNANT BENIGN TOTAL i White 685 22 707 Colored 25 25 MALE Not Given nil- 38 152 TOTAL 82ij. 60 Q8I4. White 28 1 29 FEMALE Not Given 9 5 li]- TOTAL 1 NOT GIVEN I Ii TOTAL BOTH SEXES 1 37 6 k3 k - k 865 66 931 * Eight reports could not be used. Five were not tumors; one of these was Boeck's Sarcoid. Three gave only the occupational history. (Additional information has been received on one case reported 1J.-5-52 as incomplete.) API 05481 i ) ) ) 4 Type of Tumor Site Buccal Cavity 00-09 Digest. Sys. & Perit. 10-19 Respiratory System 20-29 Gland. Epith. 00-09 11 2lk3 27 FIGURE 2 - MALIGNANT TUMORS IN MALES AS REPORTED ACCORDING TO TYPE OF TUMOR AND PRIMARY SITE Non Gland. Epith. 10-19 Leuke Lympho Nervous mias 20-29 mas Tissues 30-39 b.O-lj.9 Vascular Tissues 50-59 Muscle 60-69 NonEpith. Tissues 70-79 Embry. & Mixed Tissues 8O -89 6l 1 18 3 86 6 1 1 Tumors Not Class 90-- Total 73 0 2 272 3 118 Breast 30-39 1 1 Genital Organs IpO--14.9 1*0 Ik Urinary System 5>0-59 21 20 Skin & Soft Tissue 60-69 lli7 Bones 70-75 6 3 2 1 9 63 1 1 lf3 3 2 1 155 2 1 13' Brain 76-79 2 2 1 Lymph. & Hem. System 8O-89 12 17 Other Sites 90-- 8 25 1 Total 357 376 12 22 k 1 API 05482 13 18 29 1 k 39 15 ik 23 82l* ) ) Type of Tuinor Site Buccal Cavity Digest. Perit. OO-O9 Sys. & IQ-19 Respiratory System 20-29 Gland. Epith. 00-09 8 1 Breast 30-39 12 Genital Organs 2 Urinary System $0-59 Skin & Soft Tissue ' 60-69 1 Bones 70-7$ FIGURE 3 - MALIGNANT TUMORS IN FEMALES AS REPORTED ACCORDING TO TYPE OF TUMOR AND PRIMARY SITE Non Gland. Epith. 10-19 Leuke Lymphomias 20-29 30-39 Nervous Tissues l+0-k9 Vascular Tissues 0=59.. Muscle 60-69 Hon- Embry. Epith. & Mixed Tissues Tissues 70-79 80-89 Tumors Not Cluss. ..9 0 --- 1 1 1 2 1 5 1 Total 1 8 2 13 k 1 6 1 Brain 76-79 Lymph. : Hem. S y s t e m 80-89 OSittheesr 90-- 1 Total 2ll 12 1 1 37 API 05483 I) FIGURE if - MALIGNANT TUMORS AS REPORTED BY SEX AND PRIMARY S IT E COMPARED V/ITII U.S.A. MORBIDITY AND MORTALITY ESTIMATES SEX Site M A L s Number Reported Per Cent of Total U.S.A.* Per Cent Cancer Cases U.S.A.-- Per Cent Cancer Deaths Buccal Cavity Digestive Sys. & Peritoneum 1 Respiratory 1 System I Breast 73 8.9 10,0 272 33.0 36.0 118 lip.3 8.0 1 o.l if.7 if7 . 7 1 5 . if 0.2 | Genital Organs | Urinary System 1 Skin and I S o f t Tl a a u Q_____ 1 Bones | Brain I Lymph. & Hema1 topoietic Sys. 1 Other Sites | TOTAL 63 7.6 12.0 if3 155 13 5.2 7.0 1 8 .8 1.6 17.0 \ 18 2.2 29 39 82lf ' 3.5 if.7 100.0 j 10.0 100.0 13.0 6.6 2.2 1.3 2 . if L_1 ) 6 -5 100.0 FEMALES BOTH SEXES Number Reported Per Cent of Total U.S.A Per Cent Cancer Cases U . S . A .iH:` Per Cent Cancer Deaths Number Reporte Per Cent of Total U.S.A Per Cent Cancer Deutliu 1 2.7 2.0 1.2 7if 8.6 2. 8 21.6 23.0 38.7 280 3 2 . 5 il3.2 2 5 . if 2.0 3.9 'v 13 35.1 J _________ 1 9 . 1 if 10.8 / 51.0 23.5 1 2.7 3.0 3 . if 6 16.2 11.0 1.5 1 2.7 1 .1 1.5 1 1 2.7 ) 8.0 ) 6.2 37 100.0 100.0 100.0 120 lif 67 ifif l6l lif 18 29 ifO 86l 13.9 9.6 1.6 9.7 7.8 18 .3 5.1 5.0 1 8 .7 1.0 1.6 0 .1 2.1 2 .' -- -w* 3.if if.6 7 .if 100.0 100.0 Primary site of development of cancer among w h i t e males and females a c cording to Dorn, Harold F.: Illness from cancer in the United States. Reprint No. 2^37 Public Health Reports. (Based upon morbidity records collected from ton large cities in the United States between 1937 and 1939) ^ C a n c e r doaths by site in American Cancer Society, API 05484 the U n i t e d S t a t e s f o r 19lf8 as utilizing statistics from the prepared National by the Office Statistical Research of Vital Statistics. Section, * - 7 Mc3EE KEY-SORT CODS API CASE STUDY Banka T 1-2-3 Case Humber - Punch directly 3ank 1 - Units 2 - Tens 3 - Hundreds T 4.-5 * Company Humber - Punch as coded by Central Registry Bank ij. - Units 5 - Tens (Actual code numbers are confidential information) T -7-8-9 For Future Use Geographic Location - Punch as coded 0 - Not Specified 1 - North Eastern States: Connecticut Delaware Illinois Indiana Kentucky Maine Maryland Massachusetts Michigan New Hampshire New Jersey New York Ohio Pennsylvania Rhode Island Vermont Virginia West Virginia 'Viscons in 2 South Eastern States: Alabama Florida Georgia Mississippi North Carolina South Carolina Tennessee 3 North Central States: Colorado North Dakota Idaho South Dakota Kansas Utah Montana Wyoming Nebraska 3A - North Eastern-Central 3order States: Iowa Minnesota Missouri Ij. - South Central States: Arizona ' New Mexico Oklahoma Texas i*A - South Eastern-Central Border States: Arkansas Louisiana 5 - South Pacific States; California Nevada 5a - North Pacific States: Oregon Washington 6 - Marine Workers 7 - Pipe Lin9 Crew and Production Workers API 05487 Banks 3 1-2-3 ) - 9- Type of Timor - Punch as coded by American Cancer Society Bank 1 - Malignancy Code Bank 2 - Units) 3 - Tens ) - Eistogenic Classification Hlstogenic Classification Tumors of Glandular Epithelium (00-09) 00 01 02 03 Oij.,05 0o-08 09 - Ductal tumor - Tumor cf mucinous secreting epithelium - Papillary tumor, not elsewhere classified - Neoplastic cyst, not elsewhere classified - Functionally active tumors - Other specific glandular tumors - Unspecified tumors of glandular epithelial origin T u m o r s o f H o n g l a n d u l a r E p i t h e l i u m (11-lli.) 11 12 13 lk 15,16 - Tumor of transitional epithelium - Tumor of basal epithelium - Tumor of baso-squanous epithelium - Tumor of sauamous epithelium - ........... * Tumors of Melanin Forming Tissue (17) 17 - Tumor of melanoblast Tumors of Epithelium, not elsewhere classified (18-19) 18 - Specific tumors of epithelium, not else where classified 19 - Unspecified tumors of epithelial origin Leukemias (20-29) 20 21 22 23-25 2o 27 23 29 - Lymphocytic leukemia - Monocytic leukemia - Granulocytic leukemia - .......... - Compound leukemias - Leukemia and lymphoma - Other specific leukemias - Leukemia, type not specified API 05488 Banks 3 1-2-3 f - 10 - Type o f Tumor (C o n tin u ed ) Lymphomas (30-39) 30 - Lymphosarcoma 31 - Reticulum cell sarcoma 32 - Hodgkins disease 33 - Plasma cell myeloma 3k - Giant follicular lymphoma 3365 - - Compound lymphomas 37 - 38 - Other specific lymphomas 39 - Lymphoma, type not specified Tumors of Nervous Tissues and Associated Structures (if0-[(.9 ) Lo - Tumor of ganglion lj.1 - Tumor of sympathicoblast 1.2 - Tumor of neuroepithelium 43 - Tumor of paraganglion 4J4. - Argent affinoma ' ij.5 - Tumor of peripheral nerve sheath 40 - Timor of meninges 47 - Tumor of glia 4.3 - Other specific tumors of nervous tissue and structures i^9 - Unspecified tumors of nervous tissue origin Tumors of Vascular Tissue (50-59) 50 51 52 53 54 55-57 58 59 - Tumor of blood vessel - Hemangiomatosis - Multiple hemorrhagic hemangioma of kaposi - Tumors of specialized vascularstructures - Tumor of lymph vessel - .......... - Other specific tumors of vascular tissue - Unspecified tumors of vascular tissue origin Tumors of Muscle (66 -6 9 ) 66 - Tumor of smooth muscle 67 - Tumor of striated muscle 68 - Other specific tumors of muscle 69 - Unspecified tumors of muscle origin API 05489 Banks B 1-2-3 -- 11 -- Type o f Tumor (C o n tin u ed ) Tumors of Connective Tissue (70-77) 70 - Tumor of fibrous tissue 71 - Tumor of mucinous connective tissue 72 - Tumor of lipoid tissue 73 - Tumor of cartilage 74 - Giant cell tumor 75 - Ewings sarcoma 76 - Tumors of osseous tissue, not elsewhere classified 77 - Tumors of serous and synovial surfaces Tumors of Nonepithelial Tissues, not elsewhere classified (73-79) 78 - Specific tumors of nonepithelial tissue, not elsewhere classified 79 - Unspecified tumors of nonepithelial tissue origin Tumors of Embryonal and Mixed Tissues (8O-89) 80 - Tumor of trophoblast 81 - Tumor of embryonal gonadal tissue 82 - Tumor of teratoid tissue 33 - Tumor of epithelial and mesodermaltissues 84 - Tumor of epithelial and lymphoid tissues 35 - Tumor of mixed tissues, salivary gland type 80 - Tumor of dental tissues 87 - Tumor of mesenchyme 88 - Other specific tumors of embryonal and mixed tissues 89 - Unspecified tumors of embryonal and mixed tissue origin Tumors Not Elsewhere Classified (97-99) 97 - Tumors of uncertain histologic type - no agreement as to classification 98 - Tumors of specific tissues, not elsewhere classified 99 - Tumor, cancer, neoplasm and other general and nonspecific terms Other Conditions (XX, X8 and X9) XX - No information . X8 - Not a neoplasm X9 - Diagnosis not completed - possibly a neoplasm API 05490 Banks 3 1-2-3 1 12 - Type o f Tumor (C o n tin u ed ) Malignancy Code General Malignancy Code (Used with all Histogenic Code Numbers except Code Numbers 20-39) X 0 1 2 3 i|. - Not a neoplasm - no premalignant significance Not a neoplasm, but having premalignant significance * Benign neoplasm - no premalignant significance Benign neoplasm, but having premalignant significance Diagnosis not completed - suspected malignancy Neoplasm, malignancy not determined 5 - Malignant neoplasm, non-infiltrating (including carcinoma in situ) 6 - Malignant neoplasm, differentiated 7 - Malignant neoplasm, undifferentiated (anaplastic) 3 - Malignant neoplasm, differentiation not determined 9 - Malignant neoplasm, metastatic site Leukemia Malignancy Code (Used with Histogenic Code Numbers 20-29) $ - Aleukemic, not otherwise specified o - Chronic 7 - Acute 8 - Not determined Lymuhoma Malignancy Code (Used with Histogenic Code Numbers 30-39) 1 - Specified as benign (except the term "benign lymphoma") 6 - Single 7 - Multiple 8 - Multiplicity notstated API 05491 Primary Site - Punch as coded by Maryland State Cancer Program Bank !<. - Units 5 - Tens Buccal Cavity and Pharynx International Classification Number 00 - Lip, upper 01 - Lip, lower 02 - Lip, unspecified 03 - Tongue Oq. - Floor of mouth 05 - Salivary gland Oo - Other and unspecified parts of mouth 07 - Oral nasopharynx 08 - Nasopharynx 09 - Hypopharynx OX - Pharynx, other and unspecified parts li|.0A li|0B liiOC lip. lii-3 1k 2 114 45 lii-6 47 48 Digestive System and Peritoneum 10 - Esophagus 11 - Stomach 12 - Duodenum 14 3 - Small intestine - Large Intestine, except rectum 15 - Rectum 16 - Biliary passages 17 - Liver 18 - Pancreas 19 - Peritoneum IX - Unspecified digestive organs 150 151 152A 152B 155a 155B 157 158 159 Respiratory System 20 - Nose, nasal cavities and middle ear 21 - Accessory sinuses 22 - Larynx 23 - Trachea 24 - Bronchus and lung 25 - Media stinum 2X - Other and unspecified thoracic organs l60A 160B l6l l62A l62B I6I4. l65 30 - 3reast 170 API 05492 p rim ary S it e (C o n tin u ed ) Genital Organs International Classification Number ko - Cervix uteri U - Corpus uteri k2 - Other specified parts of uterus - Uterus, unspecified part b h . Ovary and oviduct kS - External and unspecified female genital organs h i - Prostate k8 - Testis k9 - Penis kx - Other and unspecified male genital organs (scrotum) 171 172 173 174175a ,1753 176 177 178 179A 179B Urinary System 50 - Kidney 51 - Bladder 55 - Other and unspecified parts of urinary system l80 l3lA 18IB Skin 6o - Skin of lip 61 - Skin of face, head, neck 62 - Skin of upper extremities to - Skin of trunk 6k - Skin of lower extremities 65 - Skin, unqualified Melanoma 190 A I9OB I9OC I9OD 19 0E 19 OF Other Types 191A 19 IB I9IC 19 ID I9IS 19 IF Soft Tissue 66 - Soft tissues of face, head, neck 67 - Soft tissues of upper extremities 68 - Soft tissues of trunk 69 - Soft tissues of lower extremities 6x - Other and unspecified soft tissues (Note: This group will include neoplasm of peripheral nerves which are coded to 193 of the International List.) 19 7A 19 7B 197C 19 7D 19 7E API 05493 B k-S < 1 * ** - -O - Primary Site (Continued) Bones 70 - Jaw bone 71 - Bones of head and face 72 - Bones of upper extremities 73 - Bones of trunk 7k - Bones of lower extremities 75 - Bones, unspecified site International Classification Number 19A 1963 196c 16d 1962 I96F Drain and Other Parts of Central Nervous System 76 - Eye 77 - 3rain 78 - Othercentral nervous system and intracranial nerves 192 193A 193B Lymphatic and Hematopoietic System 30 - R e t i c u l u m c e l l s a r c o m a 81 - Lymphosarcoma 82 - O t h e r m a l i g n a n t n e o p l a s m of lymphoid tissue 83 - Hodgkins disease 8k - Giant follicular lymphoma 35 - Other forms of lymphoma 86 - Multiple myeloma 87 - L y m p h a t i c l e u k e m i a 88 - Myeloid leukemia 39 - Monocytic leukemia 8x - Other and unspecified leukemia 8Y - M y c o s i s f u n g o i d e s 200.0 200.1 200.2 201 202.0 202.1 203 20k. 0 20k. 1 20k. 2 20I4..3,20I4..I4. 205 Malignant Neoplasm of Other Sites 90 - Thyroid 91 - Adrenal 92 - Pituitary 93 - Thymus 9k - Pineal 95 - Other and unspecified endocrine glands 96 - Other specified sites 9X - Unspecified sites or unknown 19k 195A 195B 195>C 195d 195E 199A 199B API 054 9 4 Banks B 6 - l6 - Stage of Disease - Punch as coded 0 - Unknown or not given 1 - Early 2 - Advanced local Regional nodes - Distant metastases 5 - Fatal termination reported B 7-8 For Future Use 3 9 Age at Onset - Punch as coded 0 - Unknown or not 1 - 0-19 years 2 - 20-29 years 3 - 30-39 years q. - J4.O-I4.9 years 5 - 50-59 years 6 - 60-69 years 7 - 70+ years given B 10 Sex and Race - Punch as coded 0 - Unknown or not given 1 - Female white 3 - Female other race . - Hale white 5 - Female unknown race 6 - Male other race 7 - Hale unknown race API 05495 Primary Petroleum Occupation - Punch as coded Bank 1 - Units 2 - Tens 00 - Unknown or not given Production 01 - Rigger and driller 02 - Well puller 05 - Others with frequent exposure to crude petroleum 06 - 07 08 - 09 - Others with infrequent exposure to crude petroleum Refining 20 - 21 - 22 23 - 2I4. - 25 - 26 27 23 29 - Catalytic cracking (includes thermal cracking of catalytic feeds) - Operators Catalytic cracking (includes thermal cracking of catalytic feeds) - Laborers, still cleaners, etc. Thermal cracking - Operators Thermal cracking - Laborers, still cleaners, etc. . Coking operations - Operators Coking operations - Laborers, still cleaners, etc. Blending of heavy fuel oils (#3-6) Blending of heating oil #2 Others on cracking operations 30 - Refining and blending of lubricants - Operators 31 - Refining and blending of lubricants - Laborers, still cleaners, etc. 32 - Packaging of lubricants 33 - Manufacture and packaging of greases 3k - 35 - Others - Lubricants and greases 36 - Refining and filtration (Pressing or centrifugation) of paraffin - Operators 37 - Refining and filtration (Pressing or centrifugation) of paraffin - Laborers, still cleaners, etc, 33 - Packaging of paraffin 39 - Others - Paraffin API 05496 - 13 - Primary Petroleum Occupation Refining (Continued) Distillation of crude oil - Operators SS I Distillation of crude oil - Laborers, still cleaners, etc. hZ - Production of asphalt - Operators k3 - Production of asphalt - Laborers, still cleaners, etc. I:7 - L8 - 9 - Straight run distillations - Others 50 - White oil manufacturing - Operators 51 - White oil manufacturing - Laborers, still cleaners, etc. 52 - 56 - Petro-chemical operations - Operators 57 - Petro-chemical operations - Laborers, still cleaners, etc. 58 - . 59 - Special products - Others 60 - Maintenance - Pipe Fitters 61 - 62 - Maintenance - Boilermakers 63 - Maintanance - Mechanics 6L - Maintenance - Tank cleaners 8: 67 68 - 69 - Maintenance - Others > 70 71 - Loading department 72 - 78 - Control laboratory 77 - 78 - 79 - Others not otherwise Refining Operations specified - General API 05497 Primary Petroleum Occupation (Continued) Transportation 80 - 81 82 - 85 - Pine line workers 86 - Marine division - Transportation of light and medium distillates (end boiling point < 650) 87 - Marine division - Fuel oil carriers 88 - Fuel oil carriers - Others 39 - Transportation - Others Marketing and Executive 90 - Service stations 91 92 - 95 - Others - Office workers, etc, 96 - Others (Not included in the four main divisions) 99 - Job to be described in detail on card Secondary Petroleum Occupation - Coded as for Primary Petroleum Occupation (See page 17) Bank j3 - Units Tens API 05498 - 20 Principal petroleum Product Contact - Punch as coded (Note: If only one product is listed and if the exposure is described as rare, infrequent or light, the information will be punched only in the secondary petroleum contact field - Bank L-o.) 0 1 2 3 - Ij. 5 - 6 7 - 8 9 - 10 11 - No contact or casual contact Not given or unspecified petroleum products Crude petroleum, reduced crude, asphalts Gasoline, light ends and solvent naphthas (i^OO0 P.) , , Medium distillates (ij.00-650o F,) Lube distillates and related uncracked intermediates (600-1000 F.) Refined products Products derived from thermal cracking units in refineries before or without catalytic cracking (600-1000 F.) Products derived from coking operations (?600F.) Products derived from catalytic cracking and reforming processes or from thermal cracking units in refineries with catalytic crackers (600-1000 F,) Chemical additives Petro-chemicals Secondary Petroleum Product Contact - Coded as for Primary Petroleu Product Contact Bank L-5 Approximate Number of Years Employed in the Petroleum Industry Prior to Onset - Punch as coded 0 - Unknown or not 1 - 0-1 year 2 - 2-ij. years 3 - 5-9 years 4- - 10-lq. years I - 15-19 years 6 - 20+ years given API 05499 ganks R 1-2 R 3 R i; - 21 y Principal Other Occupation - Punch as coded Bank 1 - Units 2 - Tens ' 00-09 - Professional and Semi-professional 10-19 - Proprietors 20-29 - Skilled Labor 30-39 - Sales and Service ij.O-ij.9 - Factory Workers and General Laborers 50-59 - Miscellaneous Approximate Number of Years Employed at Principal other Occupation - Punch as coded 0 - Unknown or not 1 - 0 -1 year 2 - 2 -L years 3 - 5-9 years - 1 0 - 1 ij. y e a r s 5 - 15 -19 years 6 - 20+ y e a rs given Primary Irritant Other Than Petroleum - Punch as coded Physical Agents 1 - Trauma 2 - Radiant Heat Solar Rays Ultraviolet Rays 5 - Radioactive Substances or Roentgen Rays Inorganic Substances 6 - Arsenic 7 - Chromates 8 - Others (Specified in detail) Organic Substances 9 - Aromatic Amines 10 - Tar or Pitch 11 - Soot 12 - Creosote and Anthracene Oils 13 - Others (Specified in detail) API 05500 B 5 y 22 Approximate Number of Years Exposed to Primary Irritant Other Than Petroleum - Punch as coded 0 1 2 - 3 ij. 5.- o - Unknown or not 0 - 1 year 2-l years 5 -9 years IO-I4. years 1 5 -1 9 years 20 + years given R 6 Secondary . Irritant other Than Petroleum - Punch as coded for Primary Irritant Other Than Petroleum - BankR-4 page 2 1 R 7 Approximate Number of Years Exposed to Secondary Irritant Other Than petroleum - Punch as coded 0 1 2 3 If. - 5 o - Unknown or not 0 -1 year 2 -1; years 5 -9 years 10 -lq. years 15-19 years 20+ years given API 05501 'A.v.v. ,V O w L A -' ((TTERINS LARORATORT CE OF MEDICINE-- EDEN AVENUE NNATI I * . OHIO UNIVERSITY OF CINCINNATI DEPARTMENT OF PREVENTIVE MEDICINE AND INDUSTRIAL HEALTH November 24, 1952 CABLE ADDRESS: KETLAR. CINCINNATI TELEPHONE: CAfitol M U Mr. D. V. Stroop, Director Department of Technical Services American Petroleum Institute 50 West 50th Street Nev York City 20 Dear Mr. Stroop: For your information I am sending you herewith a statement of expenditures made on behalf of American Petroleum Institute for the third quarter of 1952. I believe that the statement will be self-explanatory, but if you have any questions or comments, Doctor Kehoe would appreciate your bringing them to his attention. Very truly yours E. R. Fortlage, Secretary to Dr. Kehoe ef Snc API 05503 UNIVERSITY OF CINCINNATI KETTERING LABORATORY ACCOUNT OF -AMERICAN PETROL&UM INSTXI'Utjs cno 3rd- Quarter 1952____________ S A L A R IE S (Based on Proportion of Time Actually Spent on Project) Direct Salaries...................................................................................... .8S.9.4...62___ Indirect Salaries H istopathologica I Preparation.......................................... ?r.9.?.*.9.9....... Other Services............................................................ 8 1 7 3 . 1 6 ____ 1 3 .1 6 .7 8 MISCELLANEOUS EXPENSE Purchase of Animals....................................................................................................... Special Laboratory Supplies...........................................................................................- Travel .................................................................. ............................................................. Overhead (Proportion of Heat, Gas, Electricity, Steam, Telephone, General Laboratory Supplies, Postage, Annuities, Pensions, Maintenance, etc................................. 550*80 4 7 2 .8 9 552*26 *1305.80 T O T A L ............................. 2 4 ,0 4 4 .5 3 Balance Available for Further Work at End o f 2 n d . . u a t e r . . . l 2 5 2 ____________ 8, 387.02 Balance Due Kettering Laboratory at End of...................................................................... Receipts . . . J . U l y . . . l 9 5 2 --------------------------------------------- Balance Available ............... Expenditures .3r.cL.iuar.tejr.............. 24,04.4*53. Balance Available for Further Work at End o f . . . 3 r . . Q u a r t e r . ..1 9 5 2 ...* .--..-...*.. 3 4 , 3 4 2 . 4 9 Balance Due Kettering Laboratory at End of....................................................................... FORM 12)0 X KIT LAB $00 7-92 API 05504 Decenter 16, 1952 To Members Research Project Advisory Committee I am attaching the minutes of the Fourth meeting of the Research Froject (MC-1) Advisory Committee which was held in Chicago September 2I4., 1952. The Research Froject Advisory Committee will hold its next meeting at the Kettering Laboratory in Cincinnati Friday, January 16, 1953 commencing at 9:30 A.M. Eastern Standard Time. I would greatly appreciate receiving promptly from the members suggested items to be included on the agenda which will be circularized prior to the meeting. Very truly yours, MNN-.RMS ENCLOSURE 5v-W Adesis L. ft; Dq aid, 7T. Kluffei-BtTIB, H .D . .R. E^.-Eckardt,, T. M. Fraaifr, -Mvfr. D . M . H1r t -R t M. Lando-n S . K . Linder-, -g-. Q. Macfeeuzle .R.-. Xithoff Members and Associates - Subcommittee on Carcinogenicity Members and Associates - Medical Advisory Committee Dr. R. A. Kehoe Dr. A. W. Horton Dr. J. J. Fhair Mr. D. V. Stroop API 05505 Fourth Meeting R.P.A. CCWiITTEE (MC-1) Chicago, Illinois - Sept. 21+, 1952> 10:00 a.ra. D.S.T. Conrad Hilton Hotel Room 523 AGENDA 1. Consideration of the various items listed in the report to be made on 9-25-52 by the Subcommittee on Carcinogenicity to the Medical Advisory Committee, including progress reports by Dr. R. A. Kehoe, Dr, A. W. Horton, and Dr. J. J. Phair. (Copies of the reports have been circularized by Mr. Stroop.) 2. For information and any action that may be indicated. (a) Letter of August 26., 1952, from Mr. G. G. Rumbergor to Mr. Elmer 0. Mattocks. \To>n (b> Letter of August 13, 1952, bs*i Col. S. J. Auld io Dr. M. N. Newquist. (c) Letter of September 10, 1952, from Dr. R. Eckardt to Dr. M. N. Newquist. 3. Othei* I4.. Time and place of next meeting. Respectfully submitted, E. W. Adams L. C. Beard, Jr. Kieffer Davis, M.D. R. E. Eckardt, M.D. T. M. Frank, M.D. C. H. HIne, M.D. D. V. Stroop (2) R. A. Kehoe, M.D. (3) M. N NEWQUIST, Chairman R. M E. K K. G R. C R. M Landon Linder, M.D. Mackenzie MIthoff Shepardson API 05506 Per Information Cnlv - Not For Publication Research Project MC-1 Advisory September 2!, 1552 Conrad Hilton Hotel Chicago, Illinois Committee EMBERS PRESENT M. N. Newquist, M.D. - Chairman R. *4 Sckardt, M.D. - Acting Sec'y. w7 w. Adams L. nw Beard, Jr. Kieffer Davis, M.D. T. K. Prank, M.D. c-. M. Landon E. K. Linder, M.D. K. Cr. Mackenzie R. C. Mithoff R. M. Shepardson MEMBERS ABSENT AND NOT REPRESENTED C. M. Hine, M.D. OTHERS PRESENT k D. R. C. H. W. A. W. R. A. --* C. A. C. J. J. Bent - Cole - Gerarde.M.D. - Horton - Kehoe, M.D.- Mattocks - Pabst - Fhair, M.D.- Atlantic Refinign Company Phillips Petroleum Company Standard Oil Development Co. University of Cincinnati University of Cincinnati American Fetroleum Institute Socony-Vacuum Oil Co., Inc. University of Cincinnati API 05507 The attached agenda of the meeting, which had been distributed by Dr. Newquist prior to the meeting, was used as the program. rygM x The report of the Subcommittee on Carcinogenicity to be presented to the Medical Advisory Committee on September 25, 1952, was reviewed. This report, which had been sent to members of the Subcommittee on September 11, 1952, had received approval by the ^Subcommittee. The final tabulation of the voting on epidemiological studies of cancer among employes of customers was as follows: Do you recommend that Kettering Laboratory, University of Cincinnati, make epidemiological studies of cancer among employes of customers? Yes 12 No 12 Not voting 1 If yes, what is your opinion on the following points? a. Random selection of plants for survey. Yes 3 No 6 Not voting 3 b. Limit surveys to plants where cancer cases are allegedly due to petroleum products. Yes 6 No 0 Not voting 6 c. Maintain a cancer registry wherein only cancer cases proven to be due to exposure to petroleum products would be recorded. Yes 5 No 2 Not voting 5 DR. HCETON'S RDFCRT - ^ Dr. Horton used as the basis for his discussion the m e m o r a n d u m from Kettering Laboratory, dated September 21+, 1952, w h i c h h a d been distributed to members of the Medical Advisory API 05508  -MS m a p s ere n e st im portant f e a t u r e s t r e s s a o.a s e r a ' a a i o n t h a n t h e r e a r e n o n - c a r e t r o c a n t e t ..ls ; ohan Is to say th a t apparent t o e a r m c u t s u c h a n e x t r e m e d e c r e e ex' r a u n ite o i l in order to e lim in a te she c a 3 '^1C'1 C f C s, Y 1 hiC G GGn. 3 t r 6 3 S C t lI-3 3 o 3 il _ 1 pY ^ - 7 9 . T r i e r ' e we.3 c o G S i G e r a c i s g i s c g `use vest toe nature of AI1--10C ana At !- them dot .net, feel than nha specie ic grav that, t h e s e r e p r e s e n t e d a typ o oi c t o a n d o n t h e n a r k e t i n v a s oirp ria 0 o--- c f \ t e a r t h e s e o i l s w e r e t a k e n o a t 01 3GthO IT i n c a m a i n t e s n e n g i n e s . rib r t o 1: . s u g g e s t e d t h a t b e c a u s e c i t h e t e g c t l s a r e c a l r r a d on r i c e , in miurit rane r l a on r a b b i t s i n c e t i e d n g l i s h at t i e i m p o r t a n c e o f r a b b i t s m s k : r. no oas n e x t a c o n s i d e r a t a l o amount n i c h h a r e i n d i c a t e d t h a t d c d e c y l ,r:z6C- c r o n t r a s k i n of t h e r o u s e trinicn s e e m s t Oj t r u l y c a r e 1 n o g l e c o m p o u n d s , i d e s e c o n c a g e 2 9 o f t h e a n n i d a r s i ' mma r y t i l t l o g i c a l e - p e :;' - rt e n t s d a t e d S e p t e m b e r , _~ o d e c yl d er:ze ne c an ag t U s ci e r i on t o 7 -ev -, V-d i e a t e d A~p s x x e r i m e r i t a a e experiments indicate that If the skin is sensitized with icdec benzene trior to the application of AFI-9, the average latent reeled of tumor Induction is approximately l/? of what it :s v this sensitization process is not carried out. It is f:on at: accumulating tody of data of this nature that Dr. forte:" ^q n pc :ng the concept that certain materials contain accelera''Cl'S cc carcinogens. It is believed by Dr. Horton that these a( are particularly important in what he designates as sidt- q p v- p p and are of considerably less importance in residua. T;:\-.3 C.6 r.. found that an oil which has been prepared by distlllati.:n vsi c' xc benzpyrene, or essentially none, still has a cor.sibe:cab ie activity. The laboratory is attempting to find out the C - pj q, c classes cf compounds 'which are responsible for this act.vicy.. Dr. Horton's laboratory has developed a very *ap id m for quantitatively determining the amount of benzpyrene in an sample. This discussion led to the suggestion tnat Dr, Horten should consider performing an experiment in which a bat :hwis e solvent extraction of a typical lube stock base (for Ir 3pane e An I-5b AiI-79)Or API-10^) with subsequent testing of tie ertn and raffinate (s) would be performed. It Is felt t h a t n e t an e x p e r i m e n t might essentially remove ip and 5 ring a r o m a t i c comp leaving the 1,, 2, and 3 ring materials for testing,. Experiments are now underway to determine the effect Fun of painting once, twice or three times a week. In addin:c experiments on the effects of varying the amount cf material a a a given a p p l i c a t i o n (,i .e . frem 5-ICQ mg.) are also fainp co ed,, rre1ininary it is beginning to appear that the amenrn:  material applied each time may be significant in materials which have a considerable amount of the accelerators in them but p r o b a b l y is n o t i m p o r t a n t in those m a t e r i a l s in w h i c h these accelerators are minimal or absent. Thus, w h e n the potency of a m a t e r i a l /seems to correlate w i t h its benzpyrene content, the a m o u n t of m a t e r i a l a p p l i e d p e r a p p l i c a t i o n seems not to h ave any effect on this potency determination; but when a material seems to have a higher potency than its benzpyrene content would suggest it should have, the amount of material applied at each application may have a considerable effect on the potency determined. In a d d i t i o n to the p r e s e n c e of accelerators, Dr. H o r t o n has seme evidence to indicate that there may be inhibitors in cert a i n p e t r o l e u m products, and that these inhibitors are present in the residua of distillation processes but are absent in the side streams. This fact, correlated with certain other observations, has given some suggestive evidence, although certainly not conclusively demonstrated, that the inhibitors m a y be heavy metals or may be compounds associated w i t h the h e a v y metals. Dr. Hor t o n believes that these inhibitors probably account for the reason why crude oils are essentially r.on-carcinogenic, while gas oils prepared from such crudes m a y exhibit some carcinogenicity. It is Dr. Horton's belief that crude oils contain sufficient benzpyrene and other related carcinogens to demonstrate a significant degree of carcinogenicity, whereas, animal and h u m a n data indicate that they do not. It was Dr. Horton's intent not to pursue inhibitors very strenuously. Certain members of the committee, however, believe that the pursuit of such inhibitors mignt have very important practical considerations API 05511 to the petroleum industry and suggested that they not be abandoned lightly. . Because of the great complexity of carcinogenesis in petroleum products, which now appears to be a summation of the concentration of carcinogens, the presence of accelerators^ and the presence of inhibitors, many of the members of the committee felt that tne development of a 3imple analytical tool to test for carcinogenicity would be considerably more difficult, if not impossible, than originally believed. Thus, it was felt that carcinogenicity is not the result of a single class of compounds but rather the summation of three separate and distinct types of activity, and that, therefore, the development of an analytical tool has been considerably complicated. DR. FHAIR'5 RZPCRT -- --- ^ Dr. Fhair discussed the memorandum from the Kettering Laboratory ATI Research Project on Carcinogenicity Epidemiological Studies, dated September ZU-, 1952. This memorandum had been previously distributed to members of the Medical Advisory Committee. There was some discussion of the significance of the figures presented in Figure page 6 cf this memorandum. Dr. Fhair emphasized the importance of not drawing any conclusions from this table at the present time since the number of cases is so small. He emphasized again the necessity of collecting a large number of cases for analysis before any statistically significant differences can be demonstrated. Premature conclusions from data of this type w i l l be d e t r i m e n t a l a n d s h o u l d not be done. Dr. Phair* a s k e d for the cri t i c i s m s of ea c h of the m e m b e r s of this c o m m i t t e e and of the API 05512 Medical Advisory Committee of Che coding system which he is using 0n the case record cards, Dr. Kehoe and Dr. Phair reported that the Kettering Laboratory would be willing to undertake a critical review with abstracts of the literature on cancer as related to retroleum and that the annual cost of such bibliographic service would be 5ipu30. The Chairman of the RFA Committee then further emphasized the necessity of medical directors of petroleum companies ,who have membership on the Medical Advisory Committee submitting their cancer cases to Dr. Fhair if his work is to have any significance. If they are unwilling to submit tneir records, then this should be brought out in the open and the epidemiological side of these studies dropped now rather than attempting to continue when the lack of sufficient cases doom the project to failure before it starts. ITDM 2a The inquiry from Mr. G.G. Rumberger, Marathon Corporation, dated August 26, 1952, to Mr. 2. 0. Mattocks concerning possible carcinogenicity of petroleum waxes and Mr. D. V. Stroop's reply were presented for information with the verbal comment that contributors to the API Fundamental Research Project are not thereby entitled to reports on other API research projects. Copies of this correspondence were sent to members of the Medical Advisory Committee IT2M 2b Dr. Newquist's letter of August 13 1952, to Col.S.J. Auld concerning possible reporting in England of the research work at Kettering Laboratory was presented for information. A copy of this letter was sent to each member of the Medical Advisory Committee. API 05513  Dr. R.2. Sckardt'3 letter of September 1C, 1952, to Dr. Vewquiat commenting on the research activities of Dr. Paul Kotin of the University of Southern California on the matter of cancer and smog was discussed. It was the consensus of the R.F.A. Committee that Dr. Sckardt and any other Interested members of the committee might, as Individuals, meet Informally with Dr. Kotin at the time of the Industrial Health Conference in Los Angeles In April 1953 If they so desired* ITZM 3 - BUDGST ?0R YEAR JULY 1, 1953 - JUKE 30, 195k Dr. R. A. Kehoe submitted a proposed budget totalling $10^,073 for support of research project MC-1 for the next fisc^. year, a copy of which is attached. In executive session, tha/k.P.A. Committee recommended a reduction of $25,790, making a proposed budget of $75,203 for fiscal 1953-19514-. The following recommendations were made with respect to Dr. Kehoe's budget: I - Delete II and III to b e c o m b i n e d 25,720 IV - Reduce the total amount b y $10,000 and apply the balance to items A & 3 as deemed best. 33,130 V - Delete Items B & C and increase Item A by $6,263*00. Any change in research activities necessitated b y this reduction In the budget would be discussed b y the R.F.A. Committee with Dr. Kehoe and Dr. Horton at the next R.F.A. Committee meeting. API 05514 -9- IT5K Ij The next meeting of the R.r.A. Committee was set tentatively for January 16, 1953 at the Kettering Laboratory in Cincinnati. M. N. ilewquist, M. D . , Chairman R. S. Sckardt, M. D., Acting Secretary API 05515 A m erican P etroleum Institute SO W E S T SOTH S T R E E T NEW Y O RK 2 0 . N. Y. December 19,1952 To Members, Research Project Advisory Committee E. W. Adams L. C. Beard, Jr. Kieffer Davis, M.D. R. E. Eckardt, M.D. T. M. Frank, M.D. C. H. Hine, M.D. R. M. Landon E. K. Linder, M.: K. G. Mackenzie R. C. Mlthoff R. M. Shepardson Gentlemen: I am attaching the minutes of the Fourth meeting of the Research Project (MC-l) Advisory Committee which was held in Chicago, September 24, 1952. The Research Project Advisory Committee will hold its next meeting at the Kettering Laboratory in Cincinnati, Friday, January 16, 1953, commencing at 9**30 A.M. Eastern Standard Time. I would greatly appreciate receiving promptly from the members suggested items to be included on the agenda which will be circularized prior to the meeting. Very truly yours, M. N. NEWQUIST, Mt. ^ Chairman, Research Project Advisory Committee MNN-.RMS Enclosure me: Members and Associates Subcommittee on Carcinogenicity Members and Associates Medical Advisory Committee Dr. Robert A. Kehoe Dr. A. W. Horton /__ Dr. J. J. Phair Mr. D. V. Stroop API 05516 Fourth Meeting R. P. A. COMMITTEE (MC-l) Chicago, Illinois - Sept. 24, 1952, 10:00 a.m. D.S.T Conrad Hilton Hotel Room 523 AGENDA 1. Consideration of the various items listed in the report to he made on 9-25-52 hy the Subcommittee on Carcinogen icity to the Medical Advisory Committee, including pro gress reports hy Dr. R. A. Kehoe, Dr. A. W. Horton, and Dr. J. J. Phair. (Copies of the reports have been circularized hy Mr. Stroop.) 2. For information and any action that may he indicated. (a) Letter of August 26, 1952, from Mr. G. G. Rumberger to Mr. Elmer 0. Mattocks. (h) Letter of August 13, 1952, to Col. S.J. M. Auld from Dr. M. N. Newquist. (c) Letter of September 10, 1952, from Dr. R. E. Eckardt to Dr. M. N. Newquist. 3. Other 4. Time and place of next meeting. Respectfully submitted E. W. Adams L. C. Beard, Jr. Kieffer Davis, M.D. R. E. Eckardt, M.D. T. M. Frank, M.D. C. H. Hine, M.D. D. V. Stroop (2) R. A. Kehoe, M.D. (3) M. N. NEWQ.UIST, Chairman R. M. Landon E. K. Linder, M.D K. G. Mackenzie R. C. Mithoff R. M. Shepardson API 05517 For Information Only - Not Por Publication REPORT ON FOURTH MEETING Research Project MC-1 Advisory September 24, 1952 Conrad Hilton Hotel Chicago, Illinois Committee MEMBERS PRESENT M. N. Newquist, M.D. - Chairman R. E. Eckardt, M.D. - Acting Sec'y. E. W. Adams L. C. Beard, Jr. Kleffer Davis, M.D. T. M. Frank, M.D. R. M. Landon E. K. Linder, M.D. K. G. Mackenzie R. C. Mlthoff R. M. Shepardson MEMBERS ABSENT AND NOT REPRESENTED C. M. Hine, M.D. OTHERS PRESENT R. D. Bent R. C. Cole H. W. Gerarde, M.D A. W. Horton R. A. Kehoe, M.D. E. 0. Mattocks A. C. Pabst J. J. Phair, M.D. Atlantic Refining Company Phillips Petroleum Company Standard Oil Development Company University of Cincinnati University of Cincinnati American Petroleum Institute Socony-Vacuum Oil Company, Inc. University of Cincinnati API 05518 - 2 The attached agenda of the meeting, which had been dis tributed by Dr. Nevquist prior to the meeting, was used as the program. ITEM 1 The report of the Subcommittee on Carcinogenicity to be presented to the Medical Advisory Committee on September 25, 1952, was reviewed. This report, which had been sent to members of the subcommittee on September 11, 1952, had received approval by the subcommittee. The final tabulation of the voting on epidemiological studies of cancer among employes of customers was as follows: Do you recommend that Kettering Laboratory, University of Cincinnati, make epidemiological studies of cancer among employes of customers? Yes 12 No 12 Not voting 1 If yes, what is your opinion of the following points? a. Random selection of plants for survey. Yes 3 No 6 Not voting 3 b. Limit surveys to plants where cancer cases are allegedly due to petroleum products. Yes 6 No 0 Not voting 6 c. Maintain a cancer registry wherein only cancer cases proven to be due to exposure to petroleum products would be recorded. Yes 5 No 2 Not voting 5 DR. HORTON *S REPORT Dr. Horton used as the basis for his discussion the memorandum from Kettering Laboratory, dated September 24, 1952, which had been distributed to members of the Medical Advisory Committee. Perhaps the most important feature stressed by Dr. Horton was the observation that there are non-carcinogenic oils which are not white oils; that is to say that apparently it is not necessary to carry out such an extreme degree of refining as to produce a white oil in order to eliminate the carcinogenicity of an oil. In support, Dr. Horton stressed the results obtained with API-100 and API-99 There was considerable discussion by the associates on just what the nature of API-100 and API-99 might be since many of them did not feel that the specific gravity and viscosity indicated that these represented a type of oil which API 05519 - 3- might ordinarily be found on the market. It vas emphasized, how ever, by Dr. Horton that these oils were taken out of cans and were used presumably in certain test engines. Dr. Horton suggested that because of the negative results obtained when white oils are painted on mice, it might be advisable to test such materials on rabbits since the English are placing so much emphasis on the importance of rabbits in skin cancer testing work. There was next a considerable amount of discussion on the experiments which have indicated that dodecyl benzene has a specific irritant action on the skin of the mouse which seems to enhance the carcinogenicity of truly carcinogenic compounds. These experiments were summarized on page 29 of the tabular summary of current and completed biological experiments dated September 1, 1952. They indicate that dodecyl benzene can sensitize the skin to carcinogens even if it is applied prior to the application of the carcinogen. These results are indicated in experiments designated 221, 9, 9, 221-9, 221-9 (the first 5 samples listed in Table III, page 29). These experiments indicate that if the skin is sensitized with dodecyl benzene prior to the application of API-9,.the average latent period of tumor induction is approximately i/2 of what it is when this sensitization process is not carried out. It is from an accumulating body of data of this nature that Dr. Horton is developing the concept that certain materials contain acceler ators to the carcinogens. It is believed by Dr. Horton that these accelerators are particularly Important in what he designates as side streams and are of considerably less Importance in residua. Thus he has found that an oil which has been prepared by distil lation which has no benzpyrene, or essentially none, still has a considerable activity. The laboratory is attempting to find out the class or classes of compounds which are responsible for this activity. Dr. Horton's laboratory has developed a very rapid method for quantitatively determining the amount of benzpyrene in an oil sample. This discussion led to the suggestion that Dr. Horton should consider performing an experiment in which a batchwlse solvent extraction of a typical lube stock base (for Instance API-56, API-79 0r API-105) with subsequent testing of the ex t r a c t ^ ) and raffinate(s) would be performed. It is felt that such an experiment might essentially remove 4 and 5 ring aromatic compounds, leaving the 1 , 2,aid 3 ring materials for testing. Experiments are now underway to determine the effect on PMC of painting once, twice or three times a week. In addition, experiments on the effects of varying the amount of material ap plied at a given application (l.e. from 5-100 mg.) are also being conducted. Preliminary, it is beginning to appear that the amount of material applied each time may be significant in materials which have a considerable amount of the accelerators in them but probably is not important in those materials in which these accel erators are minimal or absent. Thus, when the potency of a material API 05520 seeos to correlate with its benzpyrene content, the amount of mate rial applied per application seems not to have any effect on this potency determination; hut when a material seems to have a higher potency than its benzpyrene content would suggest it should have, he mount of material applied at each application may have a con siderable effect on the potency determined. In addition to the presence of accelerators, Dr. Horton has some evidence to indicate that there may be inhibitors in certain petroleum products, and that these inhibitors are present in the residua of distillation processes but are absent in the side streams. This fact, correlated with certain other observa tions, has given some suggestive evidence, although certainly not conclusively demonstrated, that the inhibitors may be heavy metals or may be compounds associated with the heavy metals. Dr. Horton believes that these inhibitors probably account for the reason why crude oils are essentially non-carcinogenic, while gas oils pre pared from such crudes may exhibit some carcinogenicity. It Is Dr. Horton's belief that crude oils contain sufficient benzpyrene and other related carcinogens to demonstrate a significant degree of carcinogenicity, whereas, animal and human data Indicate that they do not. It was Dr. Horton's Intent not to pursue Inhibitors very strenuously. Certain members of the committee, however, believe that the pursuit of such inhibitors might have very important practical considerations to the petroleum industry and suggested that they not be abandoned lightly. Because of the great complexity of carcinogenesis in petroleum products, which now appears to be a summation of the concentration of carcinogens, the presence of accelerators, and the presence of Inhibitors, many of the members of the committee felt that the development of a simple analytical tool to test for carcinogenicity would be considerably more difficult, If not Im possible, than originally believed. Thus, It was felt that car cinogenicity Is not the result of a single class of compounds but rather the summation of three separate and distinct types of activity, and that, therefore, the development of an analytical tool has been considerably complicated. DR. PHAIR'S REPORT j Dr. Phair discussed the memorandum from the Kettering | Laboratory API Research Project on Carcinogenicity Epidemiological Studies, dated September 24, 1952. This memorandum had been pre- . viously distributed to members of the Medical Advisory Committee. There was some discussion of the significance of the figures pre sented In Figure 4, page 6 of this memorandum. Dr. Phair empha sized the Importance of not drawing any conclusions from this table at the present time since the number of cases Is so small. He e m p h a s i z e d a g a i n the n e c e s s i t y of c o l l e c t i n g a l a r g e n u m b e r of cases for analysis before any statistically significant differences can be demonstrated. Premature conclusions from data of this type will be detrimental and should not be done. Dr. Phair asked for API 05521 5 - the criticisms of each of the members of this committee and of the Medical Advisory Committee of the coding system which he is using on the cas record cards. Dr. Kehoe and Dr. Phair reported that the Kettering Laboratory would be willing to undertake a critical review with abstracts of the literature on cancer as related to petroleum and that the annual cost of such bibliographic service would be $4,43D. The Chairman of the RPA Committee then further emphasized the necessity of medical directors of petroleum com panies, who have membership on the Medical Advisory Committee, submitting their cancer cases to Dr. Phair if his work is to have any significance. If they are unwilling to submit their records, then this should be brought out in the open and the epidemiological side of these studies dropped now rather than attempting to continue when the lack of sufficient cases doom the project to failure before it starts. ITEM 2a The inquiry from Mr. G. G. Rumberger, Marathon Corpora tion, dated August 2o, 1952, to Mr. E. 0. Mattocks concerning possible carcinogenicity of petroleum waxes and Mr. D. V. Stroop's reply were presented for information with the verbal comment that contributors to the API Fundamental Research Project are not thereby entitled to reports on other API research projects. Copies of this correspondence were sent to members of the Medical Advisory Committee. ITEM 2b Dr. Newqulst's letter of August 13, 1952, to Col. S. J. M. Auld concerning possible reporting in England of the research work at Kettering Laboratory was presented for information. A copy of this letter was sent to each member of the Medical Advisory Committee. ITEM 2c Dr. R. E. Eckardt's letter of September 10, 1952, to Dr. Newquist commenting on the research activities of Dr. Paul Kotin of the University of Southern California on the matter of cancer and smog was discussed. It was the consensus of the R.P.A. Committee that Dr. Eckardt and any other Interested members of the committee might, as Individuals, meet Informally with Dr. Kotin at the time of the Industrial Health Conference in Los Angeles in April 1953 if they so desired. ITEM 3 - BUDGET FOR YEAR JULY 1. 1953 - JUNE 30. 1954 Dr. R. A. Kehoe submitted a proposed budget totalling $104,C73 for support of research project MC-1 for the next fiscal year, a copy of which is attached. In executive session, the API 05522 -6 - R.P.A. Committee recommended a reduction of $25,790, making a proposed budget of $78,283 for fiscal 1953-195^ The following recommendations were made with respect to Dr. Kehoe's budget: I - Delete II and III to be combined $25,720 IV - Reduce the total amount by $10,000 and apply the balance to items A & B as deemed best. 33>130 V - Delete items B & C and increase item A by $6 ,263.00. 19,^33 178^83 Any change in research activities necessitated by this reduction in the budget would be discussed by the R.P.A. Committee with Dr. Kehoe and Dr. Horton at the next R.P.A. Committee meeting. ITEM 4 The next meeting of the R.P.A. Committee was set , tentatively for January 16, 1953 at the Kettering Laboratory in Cincinnati. M. N. Newquist, M. D., Chairman R. E. Eckardt, M. D . , Acting Secretary API 05523 BUDGET OF THE KETTERING LABORATORY FOR THE INVESTIGATION OF THE POTENTIAL CANCER HAZARD OF THE - PETROLEUM INDUSTRY SPONSORED BY THE MEDICAL ADVISORY COMMITTEE of the AMERICAN PETROLEUM INSTITUTE July 1, 1953 - June 30, 1954 I. Determination of the location and extent of the cancer hazard from refinery intermediate and product streams Direct Salaries $ 4,000.00 Indirect Salaries 3>50.00 Miscellaneous Expense 2,000.00 Overhead 1,860.00 $ 11,360.00 II. Development of semi-quantitative biological testing methods for measuring the relative carcinogenic potencies of petroleum products Direct Salaries $ 3,50*00 Indirect Salaries 4,200.00 Miscellaneous Expense 2,300.00 Overhead 1,630.00 $ 11,630.00 III. Determination of the relationships between the rapidity of induction of benign and ( malignant tumors in experimental animals I I and various exposure factors such as frequency of application, dosage per application, area of exposure, number of applications, special irritant or toxic properties of the oil applied, etc. Direct Salaries $ 4,500.00 Indirect Salaries 5,200.00 Miscellaneous Expense 2,300.00 Overhead 2,090.00 $ 14,090.00 Indirect Salaries include Histcpathological Preparation and other services. Miscellaneous Expense includes purchase of animals, special laboratory supplies, and travel. API 05524 2 IV. Development of rapid analytical methods for estimating the relative carcinogenic potency of any given refinery intermediate or product A. Isolation and identification of compounds responsible for observed potency of various types of oils and determination of physical and chemical properties of these compounds which could be used in the development of a widely applicable analytical tool (including associated animal testing) Direct Salaries $12,000.00 Indirect Salaries 10,200.00 Misc-ellaneous Expense 3,050.00 Overhead 5,500.00 $ 30,750.00 B. Semi-empirical correlations with carcinogenic potencies based on the chemical or physical properties of known or suspected carcinogens in the oils (including associated aniamal testing) Direct Salaries $ 5,000.00 Indirect Salaries 3,700.00 Miscellaneous Expense 1,35.00 Overhead 2,330.00 V. Epidemiological Program $ 12, 380.00 A. Collection and correlation of data on cases of cancer among employees of the petroleum industry Direct Salaries $ 5*000.00 Indirect Salaries 3,500.00 Miscellaneous Expense 2,350.00 Overhead 2,320.00 $ 13, 170.00 3. Special investigations of cases of cancer in particular plants in the industry or among customers of the industry Direct Salaries $ 2,500.00 Indirect Salaries 1,750.00 Miscellaneous Expense 850.00 Overhead 1 ,163.00 $ 6, 263.00 C. Survey of pertinent literature on cases of* cancer occurring among workers exposed to tar or oil in their occupation Direct Salaries $ Indirect Salaries Miscellaneous Expense Overhead 2,000.00 1,400.00 100.00 930.00 $ 4,430.00 API 05525 1 D n H iw A , 19J Dr. Mkcrt A. Ktlst uaimreltj at Ciacinmtl The Batteria* lobcratary Coll0 cf Modici - Sta Ama Cincinnati 19 <*do 1 Daar DottarUhe Finumt to aartontimatti eonftraaft itk tha Unimralty otClarlnntti, coieria* th otti en inutlgitlai of th tosieltj Mi nota at action af cartata petreleoa protetta, a anelo th laatitatn'a hook in tha ananat at 1*6,372.9, Iddi repreaaata th diffama tatara* $3*,760.00 ani tha mangtelal tal of $8,387.02 u portai at ta ani af th tenoni qoartar, Jtaa 30, 1932* TtU check empiete* th yajmata tea dar tha pjnaant aontxnc t far th yanr din* Jta a 30, 1953* h r y trai? yoore, 7 arate t Or. S. a Or. K. 1 Mote to Mr. Welter: TUi e^eaditure lo to ta cfaar*ad agalnat tta Modieoi Reaearch Tuoi. ara API 05526 p t K T T U 1 N LABONATONY aja* or b i g i o n i -- m a n JJIICIHBATI I * . OHIO avbnoc UNIVERSITY OF CINCINNATI OCrAftTMfNT o r mcVCNTIVK N IO IC IN I AND INDUSTBIAL HBALTH December JO, 1952 'C A B L I A O M U I : U T LAB. CINCINNATI TBLCPHONC: C A m s c MIA Mr. D. V. Stroop, Director Department of Technical Services 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 $46,372.98, covering expenditures to he made on their behalf. Very truly yours, ef API 05527