Document oD8n9ZjEZZ59Mjmb7ddYx84Z7

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1948 Mar 22 DOC#: API022 DOCUMENT DESCRIPTION: Confidential Report of Subcommittee Carcinogenicity Presented to API Medical Advisory Committee A merican P etroleum Institute SO W E S T SOTM S T R E E T N E W Y O R K 20. N. Y. DEPARTMENT OF SAFETY March 22, 19W AIR MAIL CONFIDENTIAL To Members and A ssociates o f Subcommittee on C arcinogenicity Gentlemen: . Doctor Mclver Woody, Chairman, req u ests me to send you the enclosed copy o f h is c o n fid e n tia l re p o rt which submits a re so lu tio n designed to a c tiv a te the recommendations adopted by the Medical Advisory Committee a t i t s meeting held in Chicago on November 13, 19W . Members and a ss o c ia te s who have attended meet ings o f the subcommittee, held re c e n tly in New York, are req u estin g prompt a c tio n in the m atter; th e re fo re , i t is hoped th a t the re s o lu tio n may re c e iv e the unanimous support of the subcommittee, be adopted by the Medical Advisory Committee, and be tra n sm itte d through th e S afety Committee of the Board o f D ire c to rs to the Executive Committee o f the Board o f D ire c to rs fo r a c tio n a t the meeting scheduled to be h eld on A p ril 15, 19W, a t Washington, D.C. Very tr u ly yours, D. V. Stroop DVS:d Enc. me: For Inform ation o f Members and A ssociates of Medical Advisory Committee. For Inform ation o f Members o f S afety Committee of Board o f D ire c to rs . 0K FID 1N T IA L J REPORT OF CHAIRMAN OF SUBCOMMITTEE OR CARGINOGENICITY TO API MEDICAL ADVISORY COMMITTEE A p ril 2, 19U8 On 'behalf of the Subcommittee on C arcin o g en icity , I recommend to Medical Advisory Committee f o r tra n s m itta l to the S afety Committee o f the Board of D irecto rs and fo r adoption by the Executive Committee o f th e Board of D irectors a re so lu tio n authorizing the establishm ent of a comprehensive research p ro je c t on cancer-causing hydrocarbons as follows: "RESOLUTION "WHEREAS, in re c e n t months th e re has been widespread p u b lic a tio n of gen eral statem ents to the e f f e c t ' th a t men working around g a so lin e , coal ta r , lu b ricatin g o ils , and c e rta in dyes are exposed to cancer-causing hydrocarbons1; and, "WHEREAS, such general statem ents appear to be w ithout foundation but th e re are c o rre la te d r e s u lts of experim ental research work which in d ic a te the presence of cancer-causing hydrocarbons in some heavy c a ta ly tic cycle o ils; and, "WHEREAS, the s itu a tio n is such th a t the in d u stry is in need of a u th o ri ta tiv e inform ation on a l l phases o f the su b je c t and th a t need may b e st be met through the establishm ent of an industry-w ide research p ro je c t; NOW, THEREFORE BE IT "RESOLVED BY THE EXECUTIVE COMMITTEE OF THE BOARD OF DIRECTORS THAT: "1. The I n s titu te Is authorized to e s ta b lis h a comprehensive research p ro je c t fo r the development of fundamental fa c ts , a n a ly tic a l techniques and re la te d inform ation pertaining to cancer-causing hydrocarbons which may occur or be produced in petroleum or petroleum products. "2. The I n s t i t u t e i s au th o rized to e n te r in to an agreement w ith the K ettering In s titu te of Applied Physiology (U niversity of C incinnati) to provide neoessary f a c i l i t i e s and serv ice s and conduct th e work under a program to be estab lish ed on a continuing b asis by the Medical Advisory Committee su b je c t to approval by the S afety Committee of the Board of D irectors. "3. The S afety C oonlttee i s au th o rized to s o l i c i t c o n trib u tio n s to a s p e c ia l re se a rc h fund, o u tsid e of the API Maintenance Fund, in the amount o f $110,000 to meet the c o sts fo r the f i r s t year which w ill include $50,000 fo r non-recurring c a p ita l expenditures fo r construc tio n of extraordinary experimental f a c ilitie s a t the laboratory. "h. R esp o n sib ility fo r the continuation of the program of research is delegated to the S afety Committee of th e Board of D irecto rs which i s hereby authorized to approve and underwrite future annual budgets and to s o l i c i t c o n trib u tio n s to th e s p e c ia l re sea rc h fund os moy be necessary to meet approved budgets." In support of the re s o lu tio n , I append a c o n fid e n tia l subcommittee memorandum pertaining to the need for th is research p ro je c t. , ,, Ffclver Woody, M.D. CHAIRMAN API 04734 A merican P etroleum Institute SO W E S T BOTH S T R E E T NEW YORK 20. N. Y. AIR MAIL CONFIDENTIAL DEPARTMENT OF SAFETY ' March 2k, 19I18 To Members and A ssociates o f Subcommittee on C arcinogenicity Gentlemen: You are req u ested to s u b s titu te the enclosed CONFIDENTIAL MEMORANDUM (c o rre c ted March 2k, 19W) fo r the one which was a ttach ed to our l e t t e r o f March 22. The u n co rrected copy should be destroyed. Very tru ly yours D. V. Stroop DVS:d Enc. no: Tor I n fcarnation o f Members and A ssociates of Medical Advisory Committee. For Inform ation o f Members o f S afety Committee o f Board o f D ire c to rs . API 0 4 7 3 5 r nNFlDENTIAL APPEND DC I TO REPORT OF CHAIRMAN OF SUBCOMMITTEE ON CARCINOGENICITY MEMORANDUM -- CORRECTED MARCH 2U, 19U8 PU: REASONS FOR CARRYING OUT RESEARCH AND EXPERIMENTAL WCCRK ON HEAVY CATALYTIC CYCLE GAS OILS AND RELATED OILS. I t is v e il recognized th a t c e rta in coal ta rs cause the development of skin cancer in man. In numerous fo re ig n c o u n trie s and in sev eral s ta te s in th is country th is is recognized as a compensable d isease. During the p a st f i f t y years th e re have been more than 1,500 cases of skin cancer caused by exposure to shale o ils in England. Lavs have been passed requiring al l such cases to be rep o rted to the government in England. In c o n tra st, fev cases of skin cancer in the United S ta te s have been rep o rted to have been caused by petroleum or petroleum products. A ctually, about f i f t y cases of skin cancer caused by exposure to petroleum hydrocarbons dinring the processing of p a ra ffin vax and a fev cases of skin cancer in o il f ie ld vorkers have been reported in the United S tates. There are more than th ir te e n s ta te s th a t have lavs in e f f e c t a t th e present time making cancer caused by petroleum products a compensable d isease. During the l a s t four or fiv e years the c a ta ly tic cracking process has been put into use in the petroleum in d u stry . As a r e s u l t of c a ta ly tic cracking treatm ent of o il, large q u an tities of high-boiling frac tio n s of o il are produced. This highboiling m a te ria l has been shovn to cause cancer in experim ental anim als. Animal experimental stu d ies have been c a rrie d out in three vell-knovn h o sp ita ls and un iv ersities on th ree d iffe re n t samples of th is m aterial from three d iffe re n t petroleum companies. A ll th ree samples vere shovn to produce tumors vhen applied to the skin of experim ental animals in up to 100 per c en t of the anim als. These tumors became m alignant in most cases. Only a very mnw.11 amount of th e m a te ria l is necessary to produce cancer in an experim ental animal such as the mouse; fo r example, 15 m illigram s applied to the sk in of a mouse once a week fo r tv e n ty -six weeks produced cancer. Indiv iduals v lth ln and outside the petroleum In d u stry , including doctors and chemists in the in d u stry vfao have stu d ied the problem, are reasonably c e r ta in th a t the chemical compound 3> k--benzpyrene and r e la te d compounds p resen t in co al ta r and knovn to cause cancer are a lso p re sen t in the h lg h -b o llln g o i l fra c tio n s from ths c a ta ly tic cracking operations. I t is th erefo re f e l t th a t th is o il is capable of causing cancer in man, although no cases in en have been re p o rte d to d a te. I t is f s l t th a t one of th e reasons fo r th is i s th a t i t g e n erally takes te n or more ysar8 o f exposure to a carcinogenio m a te ria l fo r a cancer to develop in man, and since th is o il has only been in production fo r about four years, the period of exposure to th is m a te ria l has been s h o rt. F ie ld s tu d ie s in the petroleum in d u stry shov th a t sev e ra l thousand employees have d a ily or freq u en t co n tact v ith th is m a te ria l or blends of th is m a te ria l; vhlle i t is estim ated th a t tens of thousands of customers are p o te n tia lly exposed to blends of th is m a terial. The above evidence in d ic a te s th a t th e petroleum in d u stry is faced v ith a serious p o te n tia l cancer problem. There are many unanswered questions concerning the nature of th is hazard and hov i t might be prevented or c o n tro lle d . These questions can only be answered by carrying out a program of medical research along the lin e s uhieh the Medical Advisory Committee is recommending. In case more d e ta ile d inform ation is d e sire d , i t can be arranged fo r a member f the Medical Advisory Committee to d iscu ss th is q u estio n v ith members of the Safety Committee or Executive Committee o f the Board of D ire c to rs. API 04736  SAFETY COMMITTEE I OF THE BOARD OF DIRECTORS AMERICAN PETROLEUM INSTITUTE (FOR 19^6) John R. Suman (Chairman) ........ Standard O il Co. (New J e rse y ). 30R o ck efeller Plaza. New York 20, N.Y. ' ' K. S. Adams .................................. P h illip s Petroleum Co., B a r tle s v ille , Okla. B. B. A n d erso n ............................Waggoner E s ta te , Vernon, Texas. Paul G. B lazer .............................Ashland O il & R efining Co., Ashland, Ky. H. S. M. Burns ............................. S h e ll O il Co., I n c ., 50 West 50th S t . , New York 20, N.Y. B. G. F o l l i s ................................. Standard O il Company of C a l if ., 225 Bush S t., San Francisco 20, C a lif. p. N. F o r t i n ................................. Yale R efining Co., B illin g s , Mont. Jake L. Hamon...............................Cox & Hamon, Box 627, D allas 1, Texas. (Ex-O fficio - Vice President fo r Production) E. J. Henry ...................................The A tla n tic R efining Co., 26o So. Broad S t ., Philadelphia 1, Pa. B. Brewster Jennings .................Socony-Vacuua O il Co., In c ., 26 Broadway, New York U N.Y. W. Alton Jones ............................. C itie s Service C o., 60 Wall S t . , New York 5> N.Y. (Ex-O fficio - Vice P resid en t fo r T ransportation) B. L. Majewski .............................Deep Rock O il C orp., p. 0. Box 725, Chioago 90, 111. (Ex-O fficio - Vice P resid en t fo r Marketing) E. Ogarrio ..................................... The Texas C o., 135 E ast t n i S t . , New York 17, N.Y. W. L. Stew art, S r .........................Union O il Company of C a l i f ., 617 West Seventh S t ., Los Angeles lU, C a lif. V. G. V io le tte ............................. Standard O il Co. (Kentucky), L o u is v ille , Ky. 1-15-U8 Attended 3-22-U8 API 04737 i COyriHlITIAL REPORT OF CHAIRMAH OF SUBCOMMITTEE OH CABCIHOCSEHICITr TO API MEDICAL ADVISCKT COMGTTEE A p ril 2, 19^8 CT l " A ' / . I On b e h a lf o f th e S u b c o m itte e on C a r c in o g e n ic ity , I recom end, t o the M edical A dvisory C a m ltte e fo r tr a n sm itta l to th e S a fe ty Committee o f the Board o f D irectors and fo r adoption by the E xecutive C a m lttee of the Board o f D irectors a r e so lu tio n au th orisin g the establishm ent o f a comprehensive research p ro ject on cancer-causing hydrocarbons as follow s: "KESOLUTIQI "Whereas, in r e ce n t months th ere has been widespread p u b lic a tio n o f g e n e r a l sta tem en ts t o th e e f f e c t "that men working around g a s o lin e , co a l ta r , lu b rica tin g o i l s , and c e rta in dyes are exposed t o c a n c e r-c a u sin g hydrocarbons *; and, "Whereas, such g e n e r a l statem en ts appear t o be w ithout fou n d ation but th ere are c o r r e la te d r e s u lt s o f experim ental resea rch work which in d ica te the presence o f cancer-caus ing hydrocarbons in some heavy c a t a l y t i c c y c le o i l s ; and, "Whereas, th e s it u a t io n i s such th a t th e in d u stry i s in need o f a u th o rita tiv e inform ation on a l l phases o f the su b ject and th at need may b e s t be met through th e e sta b lish m e n t o f an lndus t r y - API 04738 QQjnrii>2i,i -uvL) s 2- vld a r e se a r c h p r o je c t; NOV, THEREFORE EE IT "RESOLVED BY TEE EXECUTIVE CQMCTTEE OF TEE BOARD OF DIRECTORS TEAT: ' "1. The I n s t i t u t e I s a u th o r ise d t o e s t a b lis h a comprehensive research p ro ject fa r the development o f fundamental f a c t s , a n a ly tic a l techniques and r e la te d inform ation pertain in g t o c a n c e r-c a u sin g hydrocarbons which may occur or be produced In petroleum or petroleum products. "2. The I n s t i t u t e la a u th o r ise d t o e n te r In to an agreement v lt h the K ettering In stitu te o f Applied Physiology (U n iversity of C incinnati) to provide necessary f a c i l i t i e s and serv ices and conduct th e work under a program t o be e s ta b lish e d on a continuing b a sis by the Medical Advisory Ccamlttee su b ject to approval by the S a fety Camrtttee o f the Board o f D irecto rs. "3. The S a fe ty Committee I s a u th o r ise d t o s o l i c i t c o n tr ib u tio n s to a s p e c ia l research fund, o u tsid e o f the API Maintenance Fund, in th e amount o f $110,000 to meet th e c o s ts fa r the f i r s t year which w i l l In clu de $50,000 f o r n on -recu rrin g ca p ita l expenditures for construction o f extraordinary experim ental f a c i l i t i e s a t the laboratory. "1*. R e s p o n s ib ility f a r th e c o n tin u a tio n o f th e program o f r e se a r c h Is d elegated to the S a fety Ccantlttee o f the Board o f D irectors which Is hereby a u th orised to approve and underw rite fu tu re wmiai budgets and t o s o l i c i t c o n tr ib u tio n s t o the s p e c ia l r e se a r c h fund a s may be n e c e ssa r y t o m eet approved b u d gets." II In support o f the r e so lu tio n , I append a c o n fid e n tia l subcommittee memorandum p e r ta in in g t o th e need f o r t h i s r e se a r c h p r o j e c t . M slver Wood? API 04739 REPORT OF CHAIRMAN OF SUBCOMMITTEE OH CARC3HOGEENICITY MEMORANDUM EE: REASONS FOR CARRYING OUT RESEARCH AND EXPERIMENTAL WORE OH HEAVY CATALYTIC CYCLE GAS OILS AND RELATED OILS. I t Is v e il recognized th a t c e r ta in c o a l ta r s cause the development o f skin cancer in nan. In numerous fo r e ig n c o u n tr ie s and In se v e r a l s ta t e s In t h is country t h is i s recognized as a compensable d ise a se . II During th e p a s t f i f t y y e a r s th ere have been mare than 5*000 c a s e s o f sk in cancer caused by exposure to shale o i ls in England. Lavs have been passed requiring a l l such cases to be reported to the government In England. In con trast, fe v cases of skin cancer In the United S ta tes have been reported to have been caused by petroleum or petroleum products. A ctu a lly , about f i f t y cases o f skin cancer caused by exposure to petroleum hydrocarbons during the processing o f p a ra ffin vax and a fe v cases o f sk in oancer In o i l f ie ld workers have been r e p o rted In th e U h lted S t a t e s . There are more than t h ir t e e n s t a t e s th a t have la v s In e f f e c t a t th e p resen t time making cancer caused by petroleum products a ccsipensable d isea se. During the l a s t four or f iv e years the c a ta ly tic cracking process has been put Into use In the petroleum Industry. As a r e s u lt o f c a ta ly tic cracking treatment o f o i l , large q u a n tities o f h igh -b oilin g fra ctio n s o f o i l are produced. T his h lg h -b o llln g m a teria l has been shown to cause cancer In experim ental anim als. Animal experim ental stu d ie s have been ca rried out In three vell-k n ovn h o sp ita ls and u n iv e r s itie s on three d iffe r e n t samples o f th is m aterial from three d iffe r e n t petroleum companies. A ll th ree samples vere shovn t o produce tumors when a p p lie d t o th e s k in o f exp erim en tal anim als In up to 100 per c e n t o f th e a n im a ls. These tumors became m alignant In most c a s e s . Only a very sm a ll amount o f th e m a te r ia l I s n e c e ssa r y to produce cancer In an experim ental animal such a s th e mouse; f o r exam ple, 15 m illig r a m s a p p lie d t o the s k in o f a mouse omse a week f o r tw e n ty -s ix weeks produced ca n cer. Individ uals v lth ln and ou tsid e the petroleum Industry, inclu d in g doctors and ch em ists In th e In d u stry who have stu d ie d th e problem , are rea so n a b ly c e r ta in th a t th e chem ical compound 3, k--benzpyrene and r e la t e d compounds p resen t In c o a l t a r and known to cause cancer are a ls o p r e se n t In th e h lg h b o llln g o i l fra c tio n s from the c a ta ly tic cracking op eration s. I t Is th erefore f e l t th a t t h i s o i l I s capable o f c a u sin g cancer In man, alth ou gh no c a s e s In man have been rep o rted t o d a te . I t la f e l t th a t one o f th e r ea so n s f o r t h i s la th a t i t g e n e r a lly ta k e s t e n or more y ea rs o f exposure to a c a r cin o g e n ic m a teria l f o r a cancer to d evelop In man, and, s in c e t h i s o i l has o n ly been In production for about four y ea rs, the period o f exposure to th is m aterial has been short. API 04740 ( C0HFIDMTIA1) I 2. F ie ld s tu d ie s In th e petroleum Industry show th a t se v er a l thousand employees have d a lly or frequent con tact v itb t h is m aterial or blends o f th is m aterial; w hile i t Is estim ated th at ten s o f thousands o f customers are p o ten tia lly exposed to blends of th is m aterial. The above e v id en ce I n d ic a te s th a t th e petroleum Ind u stry I s fa ce d w ith a s e r io u s p o t e n t ia l cancer problem . There are many unanswered q u e stio n s concern ing th e n atu re o f t h i s hazard and how I t m ight be prevented or c o n tr o lle d . These q u estio n s can only be answered by carrying out a program o f m edical research along the lin e s which th e M edical Advisory Consulttee i s recommending. In ca se more d e t a ile d Inform ation I s d e s ir e d , I t can be arranged fo r a member o f th e M edical A dvisory Cam nittee to d is c u s s t h i s q u e stio n w ith members o f th e S a fe ty C o o n lttee or E xecu tive Committee o f th e Board o f D irectors. II API 04741 * % C onfidential REPORT TO THE MEDICAL ADVISORY COMMITTEE BY THE SUBCOMMITTEE ON CARCflHDGENICITY D r. M clver Woody - Chairman 1. D aring th e p a s t s i x m onths,m any a r t i c l e s have a p p e a re d in magazines and newspapers denouncing petroleum o ils as a fre q u e n t cause of c a n c e r. T here i s some b a s is fo r th e a c c u s a tio n . Our own anim al e x p e rim e n ts jnt m plafni a t th e U n iv e rs ity o f C in c in n a ti seem to b ear th is out; fo r, of the 8 sam ples of heavy g a s -o il subm itted, 2 produced cancer of th e s k in in m ice, and one sample proved to be highly carcenogenic. 2. The p re se n t s i t u a t i o n i s somewhat s im ila r to th a t which confronted th e petroleum in d u stry 23 y ears ago, when t e t ra e th y l lead was discovered to be to x ic.. F o rtu n a te ly , only one m anufacturer was d ir e c tly in v o lv ed , and th e P u b lic Health S ervice prom ptly took th e p o sitio n th a t any dangerous substance oould be handled s a fe ly once th e h azard was p ro perly evaluated and su itab le preventive measures in s titu te d . The p re s e n t h a z a rd i s much more c o m p lic a te d and a f f e c t s ev ery re fin e r and n e arly every m arketer of petroleum products. In the p resen t s ta te of our k n o w led g e,all g a s -o ils must be re garded as p o te n tia l causes of can cer, and most heavy blends are su sp e c t. Once a g ain , th e s o lu tio n l i e s in th e e v a lu a tio n of th e hazard^follow ed by th e a p p lic a tio n o f reaso n ab le sa fe guards. A P I 047 42  1 2- our* Uo t h a t re lim in ary animal experim ents have been com pleted, i t i s e s s e n tia l th a t adequate p ro v isio n be made f o r a w e ll-ro u n d e d and a l l - i n c l u s i v e program of re s e a rc h a t a c e n t r a l pointy where th e work ife*stc3xs3 a lre a d y done by s e v e ra l la rg e companies can be c o rre la te d . I t would a ls o be d e s ira b le to p rovide f a c i l i t i e s fo r th e r o u tin e t e s t i n g of o i l sam ples a t th e expense of th e nompany which su tm its them. 4. Such a program wpXq be^jfci*v e x p e n s iv e , not o n ly because th e f ie ld work must cover th e e n tir e In d u stry from d r i l l e r to consum erjbut also because th e la b o ra to ry work must ap proach the lim its o f our presen t knowledge of cancer and petroleum ohem istry. N ev erth eless, the program must . not be l e f t fo r government a g en cies to carry th ro u g h , as th ey s u re ly w i l l , i f we h e s i t a t e . R a th e r, th e s o l u t io n o f a problem which i s so p re s s in g and which concerns us so c lo s e ly should be sought by th e in d u s try i t s e l f e s p e c ia lly when th e i n d u s t r y vthaafc h a s been so s u c c e s s f u l i n o rg a n iz in g and su p p o rtin g re s e a rc h in a p p lie d sc ie n c e . 5. The p ro p o se d program h as th e fo llo w in g o b je c tiv e s : M edical on a . To o b ta in a c c u ra te in fo rm a tio n of th e in c id e n c e o f c a n c e r, p a r t i c u l a r l y of th e s k in , among w orkers in th e petroleum in d u stry and to c o rre la te the data w ith the frequency of exposure to various petroleum products. API 04743 V b . To t e s t sam ples o f p ro d u c ts which may be c a rc in o g e n io t o s tu d y any changes th e y may produce in th e c e l l s of th e sk in and c o rre la te th ese w ith th e e a r lie s t signs of m alignancy. Chemical c. To d e v is e p h y s ic a l and c h em ical t e s t s which w i l l show whether a given o il contains caroBnogens. d. To dev elo p r e f i n i n g p ro c e s s e s which w i l l d e s tro y any c arcen o g en s w hich may be p r e s e n t. e . To d is c o v e r ways t o ? amove carcen o g en s from Mae f i n ish ed p ro d u cts or n e u tra liz e th e ir a o tio n by th e ad dition of in h ib ito rs. 7 . Such a program w ill c a ll for th e b est so rt of cooperative r e s e a r c h b ased on a b ro ad knowledge o f s t a t i s t i c s ,f c a n c e r, and c h e m is try . At th e moment i t seems d o u b tfu l w hether any one i n v e s t i g a t o r can be found who h a s a l l t h e s e q u a l i f i c a t i o n s . I t w ould seem more l i k e l y th a t two f u ll- tim e men w i l l be needed; one a p h y s ic ia n who i s i n t e r e s t e d in canoer and h a s had some e x p e rie n c e i n p u b lic h e a lth work, th e o th e r a c h em ical e n g in e e r who h as had e x p e rie n c e i n the petroleum in d u stry or perhaps a biochem ist. B. I t i s recommended t h a t a o e n te r of i n v e s t i g a t i o n and r e search on cancer in the petroleum in d u stry be estab lish ed at the U n iv ersity of C incinnati under the guidance of P ro fe s s o r R obert A. K ehoe^w ith two f u l l - t i m e i n v e s ti g a t o r s together w ith the neoessary s e c re ta ria l and tec h n ic al as s i s t a n t s . One i n v e s t i g a t o r would be chosen on th e b a s i s of h is knowledge of cancer and epidem iology; th e o th er of would be chosen on th e b a s is of h is know ledge^chem istry and r e f i n i n g p r o c e s s e s . The a c t i v i t i e s of b o th w ould be API 04744 > * -4- co o rd in ated by D r. Kehoe a s D ire c to r of th e K e tte rin g L aboratory. I t Is e stim a te d th a t such a program would req u ire an annual ap p ro p riatio n of $60,000. A lso, I t Is recommended t h a t , i n a d d itio n to th e above, c o n trib u tio n s be sought from th e la rg e r petroleum companies to co n stru ct an anim al house on the roof of the lab o rato ry wing now b e in g g r e e t e d . With t h i s a d d i t i o n a l sp a o e / we c o u ld count on u s in g some 25# o f th e com pleted b u i ld i n g which would be s u f f i c i e n t f o r o u r p u rp o se s (s e e memorandum B ). On th e b a s is o f p re s e n t b u i ld i n g c o s t s , t h i s c a p i t a l fund need not be more th an $50,000. (I API 04745 A-pP'w o '* TO personal and 0r n fid gr . t i ?l Dr. lie I v o r -ffoed y r f irise*" *"' He: Reasons f o r ca rryin g outAexp erim en tal work on Heavy C a ta ly tic Cycle Gas O ils and r e la t e d o i l s . I t .is w e ll recognized th a t c e rta in c o a l ta r s cause th e development of skin cancer i n man. In numerous fo r e ig n c o u n tr ie s and i n s e v e r a l s t a t e s in th is country t h is i s recognized as a compensable d ise a se . ^ j ^ . . mc* T*' " 'i ' " During th e past f i f t y years th ere have been over 5*000 cases o f skin cancer caused by ejgjosore t o shale, o i l s i n England1. Lairs have been p assed that a l l such cases*.be reported t o th e government ih Shgland. In co n tra st, few cases of sk in cancer in th e U nited S ta tes havs been reported to have been caused by petroleum or petroleum products^ j jctu a l j v . about f i f t y c a s e s o f sk in cancer caused by exposure t o petrolsrumii,ye53G w8?aBring th e p r o c e ssin g of p a ra ffin wax and a few c a se s o f sk in cancer, in a i l f i e l d workers have been rep orted in th e U n ited S p a te s. There are" taore' than* t h ir t e e n s t a t e s th at have law s in e f f e c t a t th e presen t tim e making cancer caused by pe -. ... f troleum products a- compensable d is e a s e . Du ring- the- lesrrT b q r or f i v e y e a r s th e c a t a l y t i c crack in g p r o c e ss has "'been put in t o u se in th e petroleum in d u s tr y . As a r e s u lt o f c a t a l y t ic cracking treatm ent of o i l , la rg e q u a n titie s o f h ig h -b o ilin g fra c tio n s of o i l are produced. T h is h ig h - b o ilin g m a te r ia l has been shown t o cause cancer in exp erim en tal a n im a ls. Animal exp erim en tal s tu d ie s have been carried o u t i n t h r e e w e l l known h o s p it a ls and u n i v e r s i t i e s on th r e e d if f e r e n t samples o f t h i s m a teria l from th ree d iff e r e n t petroleum companies. A ll th ree samples were shewn t o produce tumors when a p p lied t o th e akin o f experim ental n lm n l in up t o 100 o f th e anim als. These tumors became m alignant .i n m ost e a s e s . Only a v e r y -- * n amount o f th e m a te r ia l i s n e c e ssa r y ^ produce cancer in an experim ental animal such as th e mouse; fb r exaqjS#,'15 m illig ra m s a p p lied t o th e kdn o f a mouse once a week fo r tTtfintjr fjf weeks produced can cer. I n d iv id u a ls w ith in and o u ts id e th e petroleum in d u s tr y , in c lu d in g d o cto rs and ch em ists i n th e in d u s tr y who have stu d ie d th e problem , are r ea so n a b ly c e r ta in th a t th e chem ical compound 3 --benzpyrene and r e la t e d compounds present in c o a l t a r and known t o cause cancer are a ls o p r e sen t i n th e h ig h -b o ilin g o i l fr a c tio n s from the c a ta ly tic cracking op eration s. I t i s th e re fo r e f e l t th a t t h i s o i l i s capable o f cau sin g cancer i n man, although no eases i n man have been rep o rted t o d a te . I t i s f e l t th a t one o f th e reasons f o r t h i s i s t h a t i t g e n e r a lly ta k e s t e n or more y e a r s o f exposure API 04746 > ? to a carcinogenic m aterial for a cancer to develop in man, and, since th is o il has only been in production for about four years, the period of exposure to th is material has been short. Field studies in the petroleum industry show th at several thousand emoloyees have daily or frecuent contact with th is xate.-ial or blends of th is m aterial; while i t is estimated that tens of thousands of customers are potentially exposed to blends of th is material. The above evidence indicates that the petroleum industry is faced with a serious potential cancer problem. There are many unanswered ques tions concerning the nature of th is hazard and how i t miyht be "-"evented or controlled. These questions can only be answered by carrying out a program of medical research along the lines which the ledical Advisory Committee is recommending. In case more detailed information is desired, i t can be arranged for a member of the iledical Advisory Committee to discuss th is question with members of the . P. I. to whom the above information goes. JPH:at ha f Dictated but not read, J. P. Holt, D, MEMORANDUM March 31, 19^8 SUBJECT: RECEIPTS AND DISBURSEMENTS - API MEDICAL RESEARCH FUND. Contributions to Fund 19^5 S o lic ita tio n 19V7 S o lic ita tio n Total $ 28,900.00 27,800.00 $ 56,700.00 Disbursements from Fund Harvard U niversity Toxicological Reviews $ 27,000.00''' Cutting Oil Derm atitis 2,500.00 U niversity of Cincinnati C arcin o g en icity Fluorine Study 6, 000.00 2 ,500.00 M iscellaneous Book f a r C o acittee Use 57.77 . 29, 500.00 8, 500.00 57.77 T otal Disbursements BALANCE ON DEPOSIT $ 38,057.77 $ 18,61^2.23 API 04748 I 0 Am e r i c a n P e t r o l e u m In s t i t u t e 5 0 W E S T 5 0 th S T R E E T N E W Y O R K 20. N Y A jrll , l?t Hr. Aadrav J . B r o w , Baoratary Craaauror l 0tm O il Coapugr, Inc. Boat* A lS * fttTOOt L oalartll 3 CMtaakjr Baar . lew * - for year ooaaldaratlos Z aaolooa eo a flio n tla l oopy o f aala t lon apgrorad and adoptad ty tha lsaoutlT Ccaalttaa of tha Beard o f Blraetora a t aaatlag hold la Vaahlagton oa April 15th. Cha raaol a tias aatharla aa tha oatahllahoant of raaaaavh y n j w t a t tta ria * l i h a ah r j ta danalop n f t m t io B yraaaad la i i t w i o , A eoafld oatlal aaaoraadus la apport of ta> raaolatioo la alao aaelaaaA. Boa w in aota t*at t&a raaolwtlaa prarldaa for a opaelal raaaareh faad to ho ralaad hy voluntary aostrihatlona oatalda of tha API Intasarne land. Tea ara laritad to oaatr lta ta to th is food ratahly la proportion to yawr aoatrltw tloa to ta Intasane* Bond. Oa th is ta si joar ahora o f ta 0110,000 w ill ha Plaaaa aaad jw r ooatrlhatloa or yoar piade to a o f alkar, Aaarlaaa tro ia n a Z aatltato, 30 tan t JOth stra o t, Bav York 20, Brv York, aa jroqptly a poaalhla. Barj tra ly yoara, John 1 . Sanan, Cham as Safety Ceoadttaa o f Board o f Blraetora API 04749 V April 20, 19*6 Safoty C oalttM o f Board of Slroetoro o/o Standard OdULO o w r ( I n J w g ) 30 In oW ollar R am m lorfc 20, i . z . avootod draft o f la tta r to la laaood ovar poar alsaotero jorsaiBt to M tt takoa t j tho t a m t li Cuaatttoo at ovttag hold d g rll 15. laoo7 fc lto r a l l l hn dlo a ll o f tho dotaila o f laaaaaaa If aa* a d d a o joa ayyroao tho draft. td API 04750 \ 1 A pril , 19*8 Saar Mr. For poor eooaldsratlaa I oaoloso eoafldoatlal copy of roeolatloa spprouod sad adopted by the laseutlT e Ccar> a ltte o o f the loord o f Blreetors a t --r*1n halA in Vashlagtoa oe April 15U . S m resolution authorises the eatahU sh o u t of raaaaroh project a t B etting L a k ra to y to develop iaforaation port a1stn< to oanear-flsnelag oampcmaiM thick aay ooour or be prodaoed la p e tr o ls . A con fid en tial asaoxuadna la support of the rooolatloa la a lso oaeloooA. Too i l l aoto that the resolution provides for a apoelal research faad to be ralaod by voluntary con trib u tion s oataldo of the A ll ttlatonaiw s FuaU Toa aro la r itod to contribute to th is fond ratably la yropartloa to your contribution to tha MUnta--ira lo a d . On th lo b asis your shsrs o f ths $110,000 111 bo . llo a so aoad poor contribution or year pledge to Laeoy Balkar, Aasr l asa Betroiona S o stlta to , 50 Most 50th S treet, low lark 20, Bev la ck , s s praa^tly as p o ssib le. Mwy tru ly years, John 1 . Sanaa, Cbalxnaa Bafoty Coaalttoo of Board o f Directors API 04751 W i # A merican P etroleum Institute SO W E S T SOTH S T R E E T N E W Y O R K 20. N. Y. CONFIDENTIAL Ay>.n o. I lifaft T- Cktt.inMB'n >faMW .. f i a f n f j r r . n m r H t t a p n-P * ^ e P tj fir i I'lf HI" I I "h"l| I Oentlciswff? <JT^n T^rMt I I ....... wy w s i l l l l _ 1 - --"1-0 V-TJ- l i ^ B u J t r OJi III A j i l i ^ a -- J t o l a d --iQ_racommend f o r t r a n a ^ - l t t w A \ t p + * - a ~ + n + jr . -s ' "IJIT n "" L-lf'r-L I111""- i il11 'f 1`tiT ~Bnm~i l~f T',>~ 1 " " 1 -- -- -- +' ' 1 * "" 11 J""* ~~ -------- T. uausing wwnyBiuia as f al l ? RESOLUTION / (^A PPRO/e r*\C&At&PTtO &X EYCUTiYe.CbT<M^Trte V+SuD WHEREAS, in re c e n t months th e re has been widespread p u b lic a tio n of g en eral statem ents to the e f f e c t th a t men working around gasoline, ta rs , and lu b rica tin g o ils are exposed to cancer- causing compounds; and 4PC'L WHEREAS, such g en eral statem ents appear to be w ithout foundation but th e re are c o rre la te d r e s u lts of experim ental re sea rc h work which in d ic a te th e presence o f cancer-causing compounds in some frac tio n s derived from the c a ta ly tic processing of petroleum; and th ere are referen ces in the medical lite r a tu r e to cases of cancer caused by c e rta in petroleum crudes and fra c tio n s; and I WHEREAS, the s itu a tio n i s such th a t the in d u stry is in need of a u th o rita tiv e inform ation on a l l phases of the su b je c t and th a t need may b e s t be met through the estab lish m en t of an in d u stry wide re sea rc h p ro je c t; HOW, TBEEEFQEE BE IT ' RESOLVED BT THE EXECUTI VE COMMITTEE OF THE BOARD OF DIRECTORS THAT; 1. The I n s titu te i s au th o rized to e s ta b lis h a comprehensive research p ro je c t fo r the development of fundamental fa c ts , an aly tica l techniques and re la te d information pertaining to cancer-causing compounds which may occur in petroleum or be produced therefrom . 2. The I n s t i t u t e i s au th o rized to e n te r in to an agreement with the K ettering Laboratory of Applied Physiology (College of Medicine, U niversity of C incinnati) to provide or arrange fo r necessary f a c i l i t i e s and serv ice s and conduct th e work under a program to be e sta b lis h e d on a continuing b a sis by the Medical Advisory Committee su b jec t to approval by the S afety Committee of the Board of D ire c to rs. A P I 04*752 I -2- 3 . The S afety Committee Is authorized to s o l i c i t c o n trib u tio n s to a sp e c ia l research fund, o u tsid e of the API Maintenance Fund, in the amount of $110,000 to meet the co sts fo r the f i r s t year which w ill include $50,000 fo r non-recurring c ap ital expenditures for construction of extraordinary experimental f a c ilitie s a t the laboratory. k. B esp o n sib ility fo r the continuation of the program of re sea rc h is delegated to the Safety Committee of the Board of D irecto rs which is hereby au th o rized to- approve and underwrite future annual budgets and to s o lic it contribu tio n s to the s p e c ia l research fund as may be necessary to meet approved budgets. Sa -oupp o rt--of tho ro o e latlo R th ere ts appended a eenflduinLlal ^jnoTfWiiiim fr~ir `hi--MniHiml A~1nmrj " n u l titmn 11irtn tn l uy 11 'Hu III 1 rT"*! I 1nnrn-- ^ --1 Very t r u i y you r fry IWUU--" mr- .............. .. n i n i ^ t-a thn Irnfi ij I* " n r 1 11 Member tT BAS. 'TTf MndlrT1 " i f T- v .'f s a t API 04753 rnNFIDENTIA.I MEMORANDUM RE: THE NEED FOR THE EROPOSED RESEARCH PROJECT. I t is w ell recognized, th a t c e rta in coal ta rs cause the development of skin cancer in man. In numerous fo re ig n co u n tries and in sev e ra l s ta te s in th is country th is is recognized as a compensable d isease. During the p a st f i f t y years th e re have been more than 1,500 cases of skin cancer caused by exposure to shale o ils in England. Lavs have been passed requiring a ll such cases to be reported to the government in England. In c o n tra st, few cases of skin cancer in the United S tates have been rep o rted to have been caused by petroleum or petroleum products. A ctually, about f if ty cases of skin cancer caused by exposure to petroleum hydrocarbons during the processing of p a ra ffin wax and a few cases of skin cancer in o i l f i e l d workers have been rep o rted in the United S ta te s. There are more than th ir te e n s ta te s th a t have laws in e f f e c t a t th e p resen t time making cancer caused by petroleum products a compensable d isea se. During the la s t four or fiv e years various c a ta ly tic processes, such as cata ly tic cracking, have been put into extensive use in the petroleum industry. In the cata ly tic treatm ent of o il, re la tiv e ly large q u antities of high-boiling fra c tio n s can be produced. This h ig h -b o ilin g m a te ria l has been shown to cause cancer in experim ental anim als. Animal experim ental stu d ie s have been c a rrie d out in th ree well-known h o s p ita ls and u n iv e r s itie s on th re e d iff e r e n t samples of th is m aterial from th re e d if f e r e n t petroleum companies. A ll th ree samples were shown to produce tumors when ap p lied to the sk in of experim ental animals in up to 100 per cent of the anim als. These tumors became m alignant in most cases. Only a very small amount of the m a te ria l is necessary to produce cancer in an experim ental anim al,such as the mouse; fo r example, 15 m illigram s applied to the skin of a mouse once a week fo r tw enty-six weeks produced cancer. Individuals w ithin and outside the petroleum industry, including doctors and chemists who have stu d ie d the problem, are reasonably c e r ta in th a t condensed ring compounds, such as 3, ^-benzpyrene and r e la te d compounds, known to cause cancer are p resen t in the hig h -b o ilin g o il fra c tio n s from the c a ta ly tic cracking operations. I t ie therefore f e l t th a t th is o il is capable of causing cancer in man, although no cases in man have been re p o rte d to d a te. I t i s f e l t th a t one of the reasons fo r th is ie th a t i t g e n e ra lly tak es te n or more years o f exposure to a carcinogenic m a te ria l fo r a cancer to develop in man, and since th is o i l has only been in production fo r about four y e ars, the perio d of exposure to th is m a te ria l has been sh o rt. F ie ld s tu d ie s in the petroleum in d u stry show th a t sev e ra l thousand employees have d a ily or freq u en t co n tac t w ith t h i s m a te ria l or blends of t h i s m aterial; while i t is estim ated th a t tens of thousands of customers are p eten tially exposed to blends of th is m aterial. The above evidence in d ic a te s th a t th e petroleum in d u stry is faced w ith a serious p o te n tia l cancer problem. There a re many unanswered q uestions concerning the nature o f th is hazard and how i t might be prevented or c o n tro lle d . These questions can only be answered by carry in g out a program of medical re sea rc h along the lin e s which the Medical Advisory Committee Is recommending. In caee more d e ta ile d inform ation i s d e sire d , i t can be arranged fo r a member of the Medical Advisory Committee to d iscuss th is q u estio n w ith members of the S afety Committee or Executive Committee of the Board of D ire c to rs. API 04754 Eeese H. Taylor President I UNION on. COMPANY OF CAUFCENIA Union O il B uilding Lob Angeles lk , C a lifo rn ia May 18, 19US Mr. John R. Suman, Chairman S afety Committee of Board of D irecto rs American Petroleum In s titu te 50 West 50th S tre e t New York 20, N.Y. Dear John: This is in answer to your l e t t e r of A p ril 28 concerning the e s ta b lis h ment of research p ro je c t to develop inform ation regarding the possible occurrence o f cancer-causing compounds in c e r ta in petroleum crudes and/or fractio n s. I t is our feelin g a t the present time th a t A PI's in te re s t in a research program to develop inform ation concerning cancer-causing compounds which may occur in c e r ta in petroleum fra c tio n s appears to have been a c tiv a te d by f e a r of fu tu re presonal damage s u its from u sers of petroleum products and possible Increases in In d u stria l accident and health l i a b i l i t i e s . In the lig h t of the very lim ite d inform ation c u rre n tly av ailab le to us on the su b je c t, we consider the a d v is a b ility of th e A PI's embarking on such a program to be highly debatable. In the c o n fid e n tia l memorandum atta ch e d to your l e t t e r i t i s s ta te d th a t c e r ta in petroleum f r a c tio n s , when ap p lied to th e sk in of a mouse once a week fo r tw enty-six weeks, produced a cancer. I t i s fu r th e r s ta te d th a t i t g e n e ra lly ta k es te n or more y ears o f exposure to a carcinogenic m a te ria l fo r a cancer to develop in man. I t would seem to ub ra re th a t an Ind iv id u al would be exposed a t re g u la r and freq u en t In te rv a ls to some carcinogenic petroleum fra c tio n fo r a period of years. In our opinion the fin a l re s u lts of the proposed program might be of academic I n te r e s t, b u t would have l i t t l e p r a c tic a l s ig n ific a n c e . Unless the S afety Committee can supply more cogent reasons fo r the need of the proposed program than were contained in th e attachm ents forwarded w ith your l e t t e r , th e Union O il Company f e e ls J u s tif ie d in d e clin in g p a r t i c i pation a t th is time. Kindest personal regards. Yours most sin ce re ly , / e / Reese ( COPY) API 04755 j\ MAY j0HNK.si:^ S tandard O il C ompany (omuxi) o K K T B. W IL S O N . o r i B I BOAKD 0 10 S outh Mich ig an A vbnuk Ch ic a g o 8 0 . T t .t - X*r 21, 1*W Mr. Laaap V tUnr, l i w U ry A M rtaw ro to la v i b i U h t a 90 V ati 50th n m t la v T to ** f t M V r* AttnhaA b m te la aur aha i s t o a a n t M tt,5 K M a n r # t o MW rtK H p a rU lsla c %a a a a w aawaia l a p a i t i M el a a r aawur '/ti >: *'** i c r - , .. . to 'xa4 W i ^ he *y*R--A- -r.a. t* Hr. M i 1 t a t o 9 la t o a f M i l 3 f, 1*4*. im fkTE* <sr ki" i--X t x . vfelefc ha a a f t o t o t o t o t o tM lilM tlr tllr | l i i f t I t a n te tir ilr saato-hu* t a Xk ip -- ` a n t ttfa v t *% M . k . cm m * *r . r ho n e * U a r r rtrh a ' * . . .wcai-^ "<rry asx an ywjrr*=w; jrc .y i^ t ''. .-a 's ia ! ii-t itlBS t i c ` .CT-'cf^las. *aA ? ` C \ X *TT API 04756 STROOP thc president W . 0 . S t m r t Braun Standard O il Company of C alifornia 225 Scab S tr e e t Ban Traacleoo 20, C alifornia Bear Mr. Irena: Tear M M * e f May 19 to Mr. t a n ha* been referred to aa t eaamas tta a llen etlea o f t a r n In the sp ecial cenosr researeh yrojeet nan eet ay by Laeey a lta r , A ealateat treem rur, mho la art o f toea ta la uaek. Baaed ayen oar expert--oo in taa ralalng o f apeolal fonda sash aa taa, a fin d I t neoaaaary te 1raves as the pareeota*ee to Be oontrlbuted 7 fu lly la t i p i t a t o i l oaapulM ever and above the peroeata#aa y i l l 7 taaa to tta M ia ta u m f a d t a w i of a t. 3 . taor ta a lla r or nae tiHupMiai a l l oanpaalea aoatrlbate to jta ja a ln t--aan f k , Oa aa averaqa aaa or toe rajor eoaqewlea fa ll to aata their eoatrlbutlona in f a ll or in pert. So eaeea ataro i t la neeeouury to rolae a atatod to ta l to carry oat aa appr oved p roject, Laeey a lta r tatae ttaoe factor into -- 1Aeration in - w f taa e f aaoonta to bo paid by o il ooapanloo. I t la r ir b a b la boo oloeel y taa roaolta boar eat taa aatiaatoa. Tory tru ly yours, STB:d 00: Mr. John B API 04757 T \ m*W*Wl OU. C O M I <W CUTCHTDL Standard OU B a lld la f 8 n francioso 20, C alifornia jrtiia Balaticna S ap artn n t a. *t*,* r t * pam# fe f 19, 1 9 Safotjr OnnTttaa o f Board a f B lroetors l-- Mnan B itro l-- k o tlta to 90 M t 50t IfeTNt H* Bav Zdrk 20, Bav Tort Toar la tta r a f A j r l l 26th, oaaBlng thla oaapaaj'a ooaftrllMtlaa o f $6,000 to a fand o f $110,000 fo r a opaoial oaaoar ra oaoroB j n > i t a t la t t a r la ! Xahoratoarj, haa B o n thaawotf? and ajapathatloallgr m i m i . Va m o li lit to la fa lx o , k a m r , W t t a y a a a a ilu f r t h a r , aa to tho Baala fa r tho aaeanl alleaataii to a, hlo la 1JH $ o f tho to ta l. Soa o r l a l a that met eoofertBatlm to tho aalntanaana f n d Boa B o n n i fo r tho Baola of thlo p roratlaa. I n a ia r , tho w n aatam la that oaaa la 5.77* and oold rajraoaoit, fo r tho oaaoar jro > e t, $6,3%7. Va 111 apjroolato Boarig frc a jcm and 111 If t h n oxpodlto la oaory oy yooalBla tha fla a l io e la ln . Jm rj tra ly jm ra , V. J . Bald O. Stooart fcrom (C0FI) API 04758  i UNIVERSITY OF CINCINNATI July 9, 1948 v /y CABLE ADOR ESS: KETLAB. CINCINNATI TELEPHONE: UNIVERSITY 2665 Mr. D. V. S t r o o p , American P e tro le u m I n s t i t u t e , 5j Vest 5 jth S tr e e t, Nev Y ork C ity 2 j . P eer Mr. S tro o p : r take p le a su re in acknow ledging re c e ip t of your l e t t e r of July w ith i t s en clo su re of the check fo r payable to the U niversity. I am o f f tom o rro w f o r a v a c a t i o n t r i p and w i l l n o t r e t u r n to my desk u n til Ju ly 2. I t so happens th a t D octor H eyroth w ill a ls o be away th ro u g h th e g r e a t e r p o r ti o n o f th e m onth o f J u l y . You w i l l r e c o g n iz e fro m t h i s t h a t we do n o t e x p e c t t o a c c o m p lis h much d u r in g July > b u t we h a v e ta k e n a s e r i e s o f s t e p s w h ic h we b e l i e v e w i l l result in our discovery of the proper personnel fo r the conduct of the a n tic ip a te d w ork. ' You w i l l p r o b a b ly b e p l e a s e d t o know t h a t v e ry good p r o g r e s s i s b eing made in th e c o n s tr u c tio n o f th e a d d itio n to th e L a b o ra to ry . A f te r many d e l a y s th e w ork s h o u ld p r o g r e s s now and we s h o u ld b e moving i n t o some o f t h i s sp a c e l a t e in S eptem ber o r e a r ly in O c to b e r, u n le s s we ru n i n t o a d d i t i o n a l d i f f i c u l t y . I p re su m e t h a t you and your a s s o c ia te s a r e l a r e of th e extrem e d i f f i c u l t i e s a sso c ia te d w ith c o n s t r u c t i o n w ork a t t h i s t i m e . We c an o n ly do o u r b e s t an d hope f o r the b e s t . * S in cerely yours FAX e f C.C. : D r . M. N. N e w q u lst M r. Lacey W alker D r . M c lv e r Woody R o b e r t A . K ehoe1, M. D Y ! l y 6 , 19*6 Jmm 23, too f p n i l ooploo f tftfofa m i f tw w * with yoor lo tta r o f A m & , w i n 3 * o tltato okoek 1 the HDBBfe Of $4?,000 I d i l l i to the ttei ^MIOlt r * f CiBOlJMOtl. k t o v t ootlolyota aoo far a tk lri ojwomto oo|7 f tto lo tta r o f A mo 19* . I# M it 0 0 ! '* K* S iM H lO t * API 04760 HS mSORATORY OF APPLIED PHYSIOLOGY " c OLL M* OF MEDICINE-- EDEN AVENUE J UNIVERSITY OF CINCINNATI CIN CINNATI IS. OHIO June c'y, 1943 CABLE ADOREES: KETLAB. CINCINNATI TELEPHONE: UNIVERSITY 2S65 Mr. D. V. S tr o o p , pne A m erican P etroleum 5-j V e s t 50t h S t r e e t , Hev Y ork C ity 2 0 . n stitu te , Dear Mr. S tro o p : I am r e t u r n i n g to you h e r e w i t h two c o p ie s o f t h e l e t t e r o f J u n e 1 5 , 1943, e x ten d in g th e scope o f o ur work f o r th e A m erican P etro leu m I n s titu te . T his has been duly exe uted by th e p ro p er o f f ic ia ls of th e U n iv e r s ity . One copy h as b e en re ta in * by th e B u s in e s s M anager of the U n iv e rsity , and an o th er has gone in to our f i l e s . I f you sh o u ld r e q u i r e a t h i r d s ig n e d copy f o r any r e a s o n , we s h o u ld be g la d to forw ard th e e x e c u te d copy a f t e r h av in g made a ty p e w r itte n copy f o r o u r own f i l e s . With k in d e s t p e rs o n a l r e g a r d s , C ordially y ours, RAX ef Enc. R obert A. Kehoe, . D i' API 04761 o 1 Am e r i c a n P e t r o l e u m In s t i t u t e 5 0 W E S T 5 0 th S T R E E T N E W Y O R K 2 0 . N. Y. June 15, 1?W Board o f D irectora U niversity o f C lic lunati CIncin n a t i 1 9 , Ohio Gentlenen: T his c n a im lca tio n la a u th o r ity t o con tin u e work and to expand the scope o f the in v e s tig a tio n o f the t o x ic it y and node o f a c tio n of certa in petroleum products according to the terns o f the agreement dated January 8, 19^6 and on th e b a s is o f th e fo llo w in g budget f o r the period ending June 30, 19^9: 1 . For n on -recu rrin g c a p i t a l ex p en d itu res $ 1*0,000 2. Tar operating expenses 50,000 $ 90,000 Upon r e c e i p t o f your approval o f th e c o n tin u a tio n and expansion o f th e p r o j e c t w ith t h i s budget we s h a l l pay you th e sun o f $65,000, the balance o f $25,000 to be p aid on January 1 , 19^9* I t Is understood th a t any balance remaining In the fund on June 3 0 , 191*9 w i l l be retu rn ed t o th e American Petroleum I n s t i t u t e , and th a t no ex cess over the am ount'of the budget i s to be o b lig a ted or spent without w ritten au th orisation . mrcvxRsirc of c m c i m n T h roq/f I ts Board t Dire By. Clerk D irectors API 04762 1 Jw 1?, 19*8 Or. B obert A. Sebo* letterin g laboratori o f Applied Jhjnialogjr ^nUepa o f MartiniTM UniTarai,ty o f H milim ati C lntlanatl 19, Ghie Bear Doetor M e Xi m y e a n te jear la tta r o f A t* 12 blob te* d elliered boro today, e* anelane foor copine o f th cootiaoatioe a^ eaaeot ehloh henne basa aigaed hy th Ireeldaat Aa etateA la th a e r e a * * , e ab ell aeaL yau a oheok la th aacmnt of $65,000 jw n p tly pai re ta ra of tee eopiee ohieh bave M a aeoepted aad approred oa ta h a lf of th Caiv araity o f C laelan atl. erjr t r a i / yow e, UT8:d co: Br. X. I . M etal et Mr. Iaoagr Vhltar Or. Jtolver ooody API 04763 1 *am 15, 19*8 Board a f Dime t a r a EhlTaraitjr a f C incinnati C incinnati 1 9 , Ohio 91111 otananlaatien 1 asth crl ty to oaotlana nork aad o axpaad tha aoopa a f tha ln v n stlja tla a a f tha teadcltgr aad aoda a f action ' af o a rta la popolava jrodacta angarilin i to tha ta n a e t tha acraaaant , datad Jaansry 8, 196 and an tha ta s ta e t tha fa llo s in i tu d ja t fa r tha ; parlod andine 30, 19*9: 1. Por w> rarn arfai o sp itai arpandttn'aa # ho,000 . eagm aas > fSo Opan ra aa ly t a f panr a p p u n ti a f tha m a Min aili ai and ' axpaaalon a f tha jr o ja s t lth th la tnfloat a a ta ll |B7 yon tha san a f $65,000, ha ta la w a a f * 5,000 to ha pald an Jemnmrj 1, 19*9. I t la darstaoA th a t aap talan as w a tn ln j In tha fnnd an Jvm 30, 19*9n l l l ha s ta n a * te tha haarleaa fv tra ls w Ih s tltn ta , and vlthost n rltta n aathorlastica. *r. Aoosptad : Clark API 04764 API 04765 . uj^ ratory or A rru to phyeiolosy or medicine-- Coen avenue UNIVERSITY OF CINCINNATI CIN CINNATI 19. OHIO June 12, 1948 CABLE ADDRESS: KETLAB. CINCINNATI TELEPHONE: UNIVERSITY 2665 Mi*. D . V . S t r o o p , fite A m erican P etro leu m =J V e st p u th S t r e e t , jjev York C ity 2 j . In stitu te , pear Mr. S troop I have d e l a y e d my r e p l y t o y o u r l e t t e r o f May 2 4 , u n t i l I s h o u ld have some f i g u r e s th a t e n a b le d me to d e a l in a d e f i n i t i v e m anner v i t h t h e q u e s t i o n s r a i s e d . I am now a b l e t o r e p l y i n t e l l i g e n t l y . pursuant to our c o n v e r sa tio n s and co rresp o n d en ce, I had th e n ecessa ry d raw in gs made by our a r c h i t e c t , and th e a d d it io n a l f a c ilit ie s req u ired in co n n ection w ith the A .P .I . p r o jec t have been put to th e s e v e r a l c o n tr a c to r s f o r b i d s . T h ese b id s have now b een r e c e i v e d , and I now know w h a t t h e b u i l d i n g s t r u c t u r e w i l l c o s t . We are g o in g in to th e q u e stio n o f th e a d d itio n a l equipm ent req u ired fo r the conduct o f th e w ork , and on t h is I do n o t have p r e c is e f ig u r e s at th e m oment. H ow ever, I have a ssem b led a l l o f th e d a ta th a t a re a v a ila b le , and on th e b a s is of th e m ost generous e s tim a te s th a t can be made I am now s a f e i n s a y i n g t h a t n o m ore t h a n $ 4 0 , 0 J O .50 w i l l b e required fo r th e c a p ita l e x p e n d itu r e s. In f a c t , I b e lie v e th a t i t w i l l b e som ew hat u n d e r ~$4d,0OC5. 0 0 , f i n a l l y , b u t i n o r d e r t h a t we may be s a f e , th e sum o f $ 4 0 ,0 0 0 .0 0 s h o u ld be made a v a i l a b l e . I f th e r e should be any r e s id u e o f t h is sum , I can a s s u r e you th a t i t w i l l be expended in su ch a manner a s to ap p ly to th e a c t i v i t i e s in w hich you and y o u r a s s o c i a t e s a r e i n t e r e s t e d . I cannot t e l l you a t th is tim e what our expenditures w ill be fo r the prosecution of th e work d u rin g the f i s c a l y e ar which ends June 50, 1949. We s h a l l n o t be a b le to g e t our work s t a r t e d a s o f June 50 o f th is y e a r , n o r i s i t l i k e l y t h a t we s h a l l be a b le to o b ta in th e required p e rso n n e l by t h a t tim e . Our e f f o r t s a re b e in g made, and on th is phase o f th e m a tte r we hope to be a b le to r e p o r t r e a l p ro g re s s soon. However, because of th e delay in o b tain in g s u ita b le f a c i l i t i e s for our work, and because of the p o te n tia l delay in obtaining the p ersonnel to c a r r y on th e e x p e rim e n ta l w ork, we s h a l l n o t r e q u ir e th e funds contem plated f o r a f u l l y e a r 's work. I t i s e n tir e ly p o s s ib le , and in f a c t I c o n s id e r i t l i k e l y , t h a t we s h a l l n o t be a b le to g e t th e te s tin g work under way b e fo r e th e end of S ep tem b er. T h e r e f o r e , we s h a l l not employ someone to do t h i s work u n t i l we a re rea d y to b e g in i t , unless we f in d t h a t - i t i s n e c e s s a ry to ta k e on a p e rso n pro m p tly who would n o t be a v a i l a b l e to us i f we were to d e la y . On th e o th e r hand, I v is h to rem ind m y s e lf and you th a t c e r t a in o f th e members o f th e ed ical group w ere k een ly in te r e s te d in our u n d ertak in g to d ev elo p the means o f o b ta in in g co m p lete in fo r m a tio n o f a c l i n i c a l n a tu r e from the p etro leu m in d u s tr y . You w i l l remember th a t one o f you r group pointed out th a t he c o n sid er e d t h is to b e th e m ost im p ortan t a sp e c t of the p ro b lem , w h ic h , u n le s s i t w ere d o n e , m ig h t i n v a lid a t e o r r e n d er u s e le s s much o f th e r e s t o f th e w ork. So f a r a s I know we have n o t API 04766 # jUj,. D . V. S t r o o p - ( 3 / - J u n e 1 2 , 1 9 ^ 8 t t r u s t t h i s c l a r i f i e s t h e e n t i r e s i t u a t i o n fr o m my v i e w p o i n t an d I sh a ll de p le a se d to hear from you a t your e a r ly co n v en ien ce. C o rd ia lly y o u r s, RAK e f q . C . D r . M. N. N e w q u is t D r . M c lv e r Woody R obert A . K ehoe, M. D . API 04767 A m j 2k, H r . Robert A. Z aboe Zetta rin g laboratory o f Applied Physiology C allege o f Medicine U niversity o f C ln clm tl C in cin n ati 1 9 , Ohio Dear Doctor Behoe: Mssy then* far your recent 'ifl*--"* note about the funds to s o w the enlarged reesernh p ro ject. Tor your co n sid eratio n I ea e loee d ra ft o f l e t t e r \diich we propoee to hare e a s t to you to cover con tin u ation o f ngrii-- nt dated Jhnuary 8 , 19^6 I f th le 1 accep tab le to yea e eh all hate I t signed end e a s t to yon ae eooa aa th e mm o f e c s trlb o tlc n e received equals the T io n t o f the budget o f the period -- ^ " g June 30, 19^9. I t m y be jr a c tle a b le to fasrve the continuation le tte r signed nora p r a ^ tly I f you b a ilee I t m y be p o ssib le to Indicate a aanaehat -- l i a r budget fo r the fla e a l pear. I f the o a p lta l expenditures say be r e s tr ic te d to ease f l g v e Is m than #0,000, I t eeana to ne th at a s n igh t sa fe ly a sesse th at the operating budget far the f i r s t year nay be le e s than the #60,000 hioh as uaed a s the b a sis o f the pregraa. Li other ords, I f could uas the fig u res o f #b0,000and #0,000 fo r c a p ita l and operating expenses fo r the period jo, 19h9 #90,000 ending June e could saceoute anr le t t e r ae aeon as Is a v a ila b le. This n igh t euva onnel A rable tin s bananas o f the fa c t th at e nay not receiv e the r ssd n ln g #20,000 fo r eevsral ash or van n anths. Please l e t as have year euggsetlsns an the fe a s ib ility o f shoving a aoderata red nctlcn I s append ltu r ss fa r the f i r s t year. Tory tru ly you rs, ETS:d 3nc. c c : Dr. K. I . B sa q u lst Dr. MsPrer Voody MT. Lacey Walker API 04768 ---'Tl *n* * n n^i>' A. k -- yi u :- X v j l y X J-~> M K 1 ^ ' 7 ^ ^ u 'r , **-, "^iJt-t yJ'^ ~^Wk.E** ft f V +*uS~~Mj ^ J r~.JL`VUAtftA _J _rul ~-^v~.oJL- t '***- . I , ^ ^r-^XC c~ wW- j . u ^ *f j ^ z * y ~ ^ r , - v '*-* c>%J **~~i* --^---**-#" -4, --), . ~ t ? . - oa^* * ,-- 7<0 f ~~HXA API 04769 .i J77. i I) Jj c*p*JL - ~ * / " fU.... ^ -"'^` *u*"j st" ^j Xid ``'a ^ (l$t*Hr^*^*AcA*-*-*"^n,MiwP*"A--.*--. r*-w/--/A*'4<4 ?, -. >-. j J *1JtilACSZu < dJLir*-^ '* <ml iua^ i./ "*. -*r iM/JuX --3 |<yl/(_ , "7^* -* t***^t>5~^.i.^c C^" . L ib /u iU w J -w J ^ r* 4j^iu^U* "^T ,l.i.^/tf>2t lu-- X tf" ^ -*V a*^3 r^ 4**'*^ ^ f/ ^ye^uwjUvvj ^ ^J^ > u. 'jw2 f* _J I ^t 6/ Aj*#wo>JC v/ J-j- ^^ j~t <r<Z<MiSt^ . "***u-'uur > ^ .. -- ' --r ^ ~~ , ~V . /. *** : *~0 y - - 7 J V a. .j. k API 04770 PIATI Board of B iractora U nlrorsty of Cine1rasati Oantiansn: Thlfl er-- il n atioa la B a tte ri ty to B attina a c r t aad to expand th acope a f th isv aatlaatlo n of tba toodoity aad sode a f actio n of ca rta in patrolaoa jrodaota acecrdlag to tha tassa of tba agreaaaat datad im m a rj 8 , 19*6 aad o t tba ta a la o f th fodlewing budget fa r tha pariod aadlag A na 3 0 , 19h9i 1. Por aon-rararrlag capitai espanditorea t. Tot sparatine axpaoaoa 4-5^700tTfrf-&jCO<T"(b| > |d i o,oec - Open raealp t of potai aajanaloa o f tba jro ja a t l t t tfcla 1007000 (T) 4 BJ t . r . 8at uf 130 , 000 plaa tha 'haiacne of $30y e to be p a li aa 1# *9*9 I t la inatarrtnni tb a t anp belante r -- 'aln g la tba fund oa Jvam 30, 19^9 v i l i W r etn ruad te tba A strieoa P etro lasa Ib a tlta ta aad th at no zoaaa o rar tba anaci f tba W a t t la t e ha ahUgated o r apent oithont n rlttan aatherlM iloe* 1 I U. Aoeaptad aad Approvai n & s ir r or e n c T t n Throogh ita Board o f Mxeetom **_____________________________ C lark frealaat API 04771 ! i> May 17, i9 t I r . Robart A. Saboa la tt a r li Labaratory o f Appliafi Ftayalolacy Collagi o f Madieina U niversity o f C tnrlrm tl Cin tim a ti 19, C tlo Saar Doctor Eaboa: Muy ttaarira fa r ja a r nota a f May Itati and th reper o f esqpeadlture nada darlas ttaa f lr e t uartar o f 19t. Tea are acar e o! In jm or a a sta y tlo e th a t ttaa relnfearaaaant o f ttaa eoa orar apponilart aay be takan cara o f inalar th prorlalana o f toa aev and alargad p rojaet. Tou v i l i ha latarastad to laara th at goo yr c raaa la beine nada In ttaa r a lsla g <*f fonda to covar ttaa ooat o f ttaa procrea fior I f c o n trita tia o s pentirne to ba receivad e t ttaa arrent r a ta , va ataal be atala to aaaeata ttaa agriaaant p rior te Jtane 15tta. Do ja a lata te bava a nav a c r iu n t nafotlatad or H I l t ba a stle fa o to r y to axtand and aapaad ttaa acope o f ttaa ana vhleh a alead in Jtaanary 19tat Tar7 tru ly youre , DV8:d 00: i r . M. I . la a fa la t i r . Malvar Voady Mr. Laoay M a lte API 04772 M O R A T O R Y OF ARBLIED PHYSIOLOGY iTTtC"O" l`^5t, Gr El OF MEDICINE-- EDEN AVENUE * UNIVERSITY OF CINCINNATI CIN CINNATI 19 OHIO May 1 4 , 1*48 CABLE ADDRESS TELE'HO NE KETLAB CINCINNATI UNIVERSITY 2S65 Mr. D . v . E t r o o p , American Petroleum 5u West S tre e t, fjev l o r k C i t y 2 j . In s titu te , D e a r Mr. S tr o o p : I send you n e r e v ith th e r e p o r t of e x p e n d itu re s made d u rin g t h e f i r s t q u a rte r of 1948, in our p ro se c u tio n of the work on c a rc in o g e n ic ag en ts sponsored by The Am erican P etro leu m I n s t i t u t e . I am n o t a t a l l concerned as to th e manner and tim e of our reim b u rse ment of th e sum over-expended , inasm uch a s I assume t h a t t h i s w ill be taken c a re of in due c o u rse under th e p ro v is io n s of th e new and enlarged p r o j e c t . I f I am m ista k e n in t h i s , and i f any o th e r a c tio n should be ta k e n , I s h a l l e x p e c t you to l e t me know. O th e rw ise , we s h a ll c o n tin u e th e work alo n g p r e s e n t l in e s u n t i l we a re duly a u th o rized to proceed on th e l a r g e r s c a l e . Meanwhile D r. H eyroth and I a re u n d e rta k in g to f in d th e p e o p le re q u ire d to c a rry on th e larger program. Very tru ly y o u rs, R o b e r t A . K e h o e , M. E>. RAK e f C .C .i D r. M clv er Woody Enc. P. S. I t was a p l e a s u r e t o s ee y o u r d a u g h t e r , and I was very much p le ase d t h a t n o t h i n g very s e r i o u s r e s u l t e d from h e r e x a m i n a t i o n by Dr. S tev en so n . . R.A.K. T ' KETTERING LABORATORY OF APPLIED PHYSIGEGY ACCOUNT OF THE AMERICAN PETROLEUM INSTITUTE For th e F i r s t Q u a rte r of 1548 (Based on P r o p o r t i o n o f Time A c t u a l l y Spent on P r o je c t) Robert A- Kehoe - S u p e rv is io n Karl E itz m ille r - P a th o lo g ic a l A ssistan ce Sylvan W itherup - T ech n ical A s sista n c e Harold S c h le c h t - T e c h n ic a l A s s is ta n c e j l | ^ r*T,LANEOUS EXPENSE Traveling Expense - Dr. R obert Kehoe T rip to New York C ity on March 3, 1948 Conference w ith R e p re se n ta tiv e s of American ^ petroleum I n s t i t u t e M edical Committee proportion of S e c re ta ria l, L ibrary, Ja n ito rs , Wash Boys, D raftsm an , S h ip p in g C le rk s , Animal C a re ta k e rs, H is to p a th o lo g ic a l P re p a r a tio n e t c .............................................................. Proportion of H eat, Gas, E le c tr ic ity , Steam, Gas, Telephone, M aintenance, P ensions, . A n n u itie s e tc .......................................................... 50.00 150.00 58.98 39.83 298.81 86.50 180.17 129.75 695.23 B alance Rem aining f o r Work i n 1948 a t End of 1 9 4 ? ......................................................$3^9-62 E x p en d itu re s 1 s t Q u a rte r 1943 .................. 695-23 Balance due K e tte rin g L aboratory . . . $3 4 5 .6 1 API 04774 6 ^ oratory o f a pp lie d p h y sio lo g y tfTT(c*o"l1la. C*l OF NEDICINE-- EDEN AVENUE f UNIVERSITY OF CINCINNATI CINCINNATI I. OHIO August 1 J, 1^40 CABLE ADDRESS. KCTLAB. CINCINNATI TELEPHONE: UNIVERSITY 2SSS Hr. r - V S t i o o p , American Petroleum I n s t i t u t e , f -,j V est 5 -|t h S t r e e t , jew xork City 2 j . pear Mr. S tro o p : X send you h erew ith f o r your in fo r m a tio n , an account of the expenditures mede d u rin g th e second q u a r t e r of 19^3 in c o n n e c tio n with the in v e s tig a tio n of c a rc in o g e n ic ity . I n i s , I b e lie v e , is self explanatory. Cordially yours, I . o b e r t A. Kehoe,' M. D. ____ UNIVERSITY OP CINCINNATI KETTERING LABORATORY OF APPLIED PHYSIOLOGY ACCOUNT OF THE AMERICAN PETROLEUM INSTITUTE For the Second Q u arter of 1948 .,,vs (Based on P r o p o r tio n o f Time A c tu a lly -- Spent on P ro je c t) Robert A. Kehoe - S u p e rv is io n Francis Heyroth - Chemical add T o x ico lo g ical A ssistance Karl K itzm iller - P a th o lo g ic a l A ssistan ce ipyTlANEOUS EXPENSE Traveling Expense T rip to W ashington, D. C. on June 27,28 and 29, 1948 Dr. F ra n c is H ey rp th ................................................................... P ro p o rtio n of S e c r e t a r i a l , L ib r a r y , J a n i t o r s , Wash Boys, D raftsm an, Shipping Clerics, Animal C aretak ers, H is to p a th o lo g ic a l P r e p a r a tio n ................................................. Proportion of H eat, Gas, E le c tr ic ity , Steam, Gas, Telephone, M aintenance, Pensions, A nnuities etc . . . 34.61 3.19 17.30 55-10 82.46 10.12 10.23 Balance due K e tte rin g L aboratory a t end o f 1 s t Q u a rte r 1 9 ^ 8 ........................................ $3^5*61 R eceipts 7-9-19^8 For E x p e rim e n ta l P r o g r a m ............................... .2 5 ,0 0 0 .0 0 B alance Rem aining f o r Work i n 19^8 . . . 2 4 ,6 5 ^ .3 9 E x p en d itu re s 2nd Q u a rte r 1948 ...................... B alance Remaining f o r Work in 1948 . . . . ......... 157 91 24,496.48 157.91 API 04776 Il \V C t t . 4 i vJ REPORT ON THE CARCINOGENIC POTENCY OF EIGHT OILS SUBMITTED BY THE AMERICAN PETROLEUM INSTITUTE .* ! U u At th e annual m eeting o f th e M edical A dvisory Committee h e ld in November, 1947, th e p ro g re s s made in th e t e s t i n g f o r c a rc in o g e n ic ity of each of th e e ig h t o i ls se le c te d by the Subcommittee on C arcin o g en icity was re p o rte d o r a lly . Because, a t th a t tim e, th ere were s t i l l su rv iv o rs in se v e ra l of the e ig h t groups o f mice employed as t e s t an im als, no attem pt was made to p r e s e n t th e d a ta g r a p h i c a l l y . Such a p r e s e n ta tio n i s now p o s s ib l e , sin c e a l l o f th e mice have d ie d o r have been k ille d d u rin g th e p a s t y e a r. D uring th a t p e rio d , th e sample of o i l th a t had been found to be carcin o g e n ic was r e te s te d , employing f o r t h i s purpose mice o f an o th er s t r a in . C ontrol observations have also been am plified in c e rta in re sp e c ts. M aterials Tested B rie f d e s c rip tio n s of the e ig h t o i l s s e le c te d by the Subcommittee a re given in Table 1, and such p h y sic al and chem ical d a ta reg ard in g them a s have been se n t us are recorded in Table 2. Apj 04777 O ne-gallon samples of each of th e se o ils were se n t d ire c tly to the Laboratory and used in th e te s ts . A $$- g a llo n drum of each of th e s e o i l s i s b e in g s to r e d a t th e L ato n ia R e fin e ry o f th e S ta n d ard O il Company of O hio, to serve as a reserve supply in the event th a t a re p e titio n of any o f th e e x p e rim e n ts sh o u ld be deemed d e s i r a b l e a t some time in the fu tu re . A ll of th ese sto re d o ils were reblanketed by u s w ith n itr o g e n a t th e r e q u e s t of D r. M. N. N ew quist, because i t was b e lie v e d t h a t th e r e may have been s l i g h t d iffe re n c e s in th e manner in which th e drums were purged of a ir a t th e v a rio u s r e f i n e r i e s . At th e tim e the re b la n k e tin g was done i t was found t h a t a l l of th e drums were under s lig h t negative p re ssu re . For purposes of a n a ly s is , samples of gas were removed from th e 5 -in ch a i r space above th e o i l in the case o f two o f th e drums (O ils 11980 and 11885). The v a lu e s fo r th e n itro g e n content were 97.8 per cent and 97.2 per c en t, r e s p e c t iv e ly . The b a la n ce can n o t be assumed to be pure oxygen, s in c e s u l f u r d io x id e and o th e r g a se s may a ls o have been p re se n t The space above th e o i l in each drum was r e flu sh ed w ith n itro g e n , a i r being excluded by the use of a ru b b e r dam which co v ered th e opening o f each bung. In a l l % c a se s e x c e p t one (Drum 4 , O il 11896), th e drums were s e a le d API 04778 under a p o s i t iv e p re s s u re of two pounds. Drum 4 (O il 11396), w hich did not have sta n d ard f i t t i n g s , was se ale d a t atm ospheric p re s s u re . On f lu s h in g th e drum s, s tro n g o d o rs, i d e n t i f i e d o nly as due to s u lf u r compounds, were n o ted in th e case of two of th e drums (O ils N-3295-3 and - 3 6 3 1 ). In control experim ents, 20-m ethylcholanthrene, as pur chased from th e Eastman Kodak Company, was em ployed. It-s m elting p o in t was n o t f a r below th a t re p o rte d in th e l i t e r a t u r e . W hite o i l , U .S .P ., was a ls o t e s t e d . The sample (I-CC) was a c o a s ta l n ap h th en ic crude coming from a Texas Gulf crude (L e tte r of Dr. J .P . H olt, January 20, 1947). I t s p h y sical, chem ical and o th e r c h a r a c t e r i s t i c s a re g iv en in T able 3 E xperim ental Methods Animals Mice were s e le c te d a s th e ex p erim e n tal anim als f o r th e s e t e s t s b ecause th e y a re known to be s u s c e p tib le to c a rc in o g e n ic a g en ts, and because abundant data are a v a ila b le in the l i t e r a tu r e on th e e f f e c t s o f p a in tin g t h e i r sk in w ith a la r g e number of pure compounds. They o f f e r a ls o th e advantages of being tra c ta b le , of having a r e la tiv e ly short life -s p a n , and of req u irin g but l i t t l e space fo r housing. In the re p o rts of the p io n ee rin g e x p e rim e n ta l work conducted in England by Kennaway, API 04779 Cook, and o t h e r s , no m ention i s made o f th e g e n e tic o r i g in o f th e w hite mice employed. In o rd e r to minimize v a ria tio n s in s u s c e p t i b i l i t y , we d ecid ed to employ o n ly mice o f some w e llstudied inbred stra in and, a fte r consultation w ith several members of th e s t a f f of th e N a tio n a l Cancer I n s t i t u t e , we chose d a rk -c o lo re d mice o f th e C-jH s t r a i n . Spontaneous carcinom a of th e sk in r a r e ly , i f e v e r, develops in mice of t h is s t r a in . S in c e , however, carcinom a of th e b r e a s t o c cu rs q u ite commonly in fem ale C-jH m ice, only m ales were employed in t h i s work. The source o f our su p p ly o f th e s e mice was th e Jackson Memorial L ab o rato ry , Bar H arbor, Maine. A lim ite d number o f th e mice used were bred in th e L aboratory from t h i s s to c k , w hile o th e rs were used a s p u rch ased from Bar H arbor. The e x a c t age o f each mouse a t th e tim e an experim ent was begun was, th e r e f o r e , un known, but i t i s b e lie v e d th a t a l l t h e i r ages ranged between two and th r e e m onths. For purposes of com parison, one of the o i ls was a lso t e s t e d upon mice o f th e CFW s t r a i n , p u rch ased from th e Carw orth Farm s, New J e r s e y . Technique Each o i l was t e s te d upon a s e p a ra te group of 20 m ice, approxim ately 0 .1 gram of an o i l being a p p lie d upon th e sk in ApI 04780 of the back of each mouse once each week. T his freq u en cy was chosen a f t e r p re lim in a ry e x p e rim e n ts had shown t h a t under th e s e c o n d itio n s no one o f th e o i l s would be exp ected to g iv e r i s e to system ic in to x ic a tio n and so k i l l o ff th e anim als before carcinom as m ight d e v e lo p . No d e p il a t o r y was u sed and th e h a i r was not clip p ed from the back p r io r to p a in tin g th e an im als. The q u a n tity o f o i l t h a t i s r e a d i ly r e t a in e d by a cam el' s h a ir bru sh was a p p lie d by moving th e b ru sh down th e m iddle of th e back from th e neck toward th e rump. P relim in ary experim ents in which th e brush was weighed b efo re and a f t e r s tro k in g the skin in d ic a te d th a t the amount a p p lied was approxim ately 0 .1 gram, b u t no e f f o r t was made to c o n tr o l th e dosage w ith p r e c i s i o n . At no tim e were any e f f o r t s made to remove th e o i l from the sk in by w ashing. A se p a ra te b ru sh was employed f o r each o il. One c o n tr o l group o f 20 mice was s u b je c te d to a p p lic a tio n s of w ater in order to confirm the non-occurrence of sp o n taneous tum ors and to e lim in a te any e f f e c t t h a t m ight be a ttrib u te d to th e handling of the anim als. Three o th er co n tro l groups were su b je c te d to co n ta ct w ith a known, p o ten t c a rc in o genic ag en t, 20-m ethylcholanthrene, which was a p p lied as a sa tu rated so lu tio n in white m ineral o i l , a 0.3 per cent so lu tio n API 04781 in ben zene, o r a 0 .6 p er c e n t s o lu tio n in b en zen e. The l a t t e r s o lu tio n was a ls o t e s t e d upon a group composed o f 17 mice of th e CFW s t r a i n . R esults As th e ex p erim en t p ro g re s s e d , most of th e mice e x h ib ite d some l o s s o f h a i r , w hich was p a r t i c u l a r l y marked i n th e case of th o s e s u b je c te d t o c o n ta c t w ith O ils - 3 6 3 2 , W-3 6 3 1 , W-3 6 3 O, 8295-2, and 11385. In th e case o f c a rc in o g e n ic m a te r ia ls , th e re began to a p p e a r, a f t e r 12 o r more w eeks, depending upon th e nature of the m aterial applied, a lo c a liz e d thickening of the squamous e p ith e liu m in th e form of a d is c r e te w arty prominence in th e otherw ise smooth su rface o f the sk in . In se v e ra l in s ta n c e s , more th an one such outgrow th a p p eared in th e s k in o f th e same mouse. These g ra d u a lly in cre ased in siz e and p ro jec te d above the su rfa c e as h ard , warty grow ths. In a very few in s ta n c e s , they reg ressed and disap p eared . G enerally, however, they con tin u e d to grow and in some c a se s a t t a i n e d a d ia m e te r o f s e v e r a l c e n tim e te r s . When such an o u tg ro w th had a t t a i n e d a d iam ete r o f 1 mm., i t was a r b i t r a r i l y re c o rd e d a s a tum or. At weekly in s p e c tio n s of th e a n im a ls, re c o rd s w ere made o f th e number o f mice th a t (a) developed v is ib le tum ors d u rin g th e p reced in g week, (b) d ie d d u rin g t h a t tim e w ith o u t hav in g shown API 04782 a tumor, (c) died and gave v is ib le evidence of a tumor, (d) were s t i l l a liv e w ith tum ors, and (e) were liv in g w ithout tum ors. Most of the anim als th a t died were su b je cted to necropsy, a t which p o rtio n s o f the tum or-bearing sk in were removed fo r m icroscopic ex am in atio n . In a few in sta n c e s ne c ro p sie s could n o t be perform ed e ith e r because th e mice had been devoured by t h e i r cag e-m ates, o r because t h e i r tis s u e s had undergone post-m ortem decom position by the tim e they were found. The w eekly re c o rd s a re p re s e n te d in cu m u lativ e fa s h io n in the g rap h . This graph was co n stru cted during the progress of the experim ent, w ithout consideration of the re s u lts of the h is to lo g ic a l exam ination of th e tis s u e s . In a few in s ta n c e s, such exam ination d isclo sed the fa c t th a t outgrowths re corded as tumors were m erely verrucous masses of ep ithelium o r a re a s o f advanced h y p e rk e ra to s is , and not m alig n an t tum ors. The graph has n o t been c o rr e c te d so a s t o in c lu d e o n ly h i s t o lo g ic a lly dem onstrable m alignant tum ors, but the m icroscopic fin d in g s are presented in the d e sc rip tio n of th e in d iv id u al experim ental groups. C ontrol Experiments These a re p re s e n te d on th e l e f t s id e of th e g ra p h . API 04783 Water A ll of th e mice in the ex p erim en tal group su b je cted to contact w ith w ater alone died before the appearance of any outgrow th upon the s k in . (In a l l of the g rap h s, mice th a t died a t a tim e p rio r to the app^rance of any sw elling, as did a l l the mice exposed to w a te r, are in d ic a te d by the sign. 1 ) Exam ination of se c tio n s of the skin of three of th e mice o f ttis group re v e a le d no a b n o rm a litie s . The l a s t su rv iv o r in th e group was k ille d a t the end of th e ^ t h week. The absence of any tum ors in t h i s c o n tr o l group confirm s th statem ent of o th e rs th a t th e incidence of spontaneous tumors o f th e sk in of male C^H mice i s low . The most common cau ses of death were pneumonia and n e p h r itis . White M ineral O il S in ce we d e s ir e d t o employ w h ite o i l a s a s o lv e n t f o r 2 0 -m eth y lch o lan th ren e, a second c o n tro l group was su b je c te d to contact w ith w hite o il alo n e. At the beginning of the 33th week an abn o rm ality was n o ted in the sk in of one of the m ice. I t was recorded te n ta tiv e ly as a tum or, and i s in d ic a te d in th e graph by th e code . T his mouse d ied d u rin g th e fo llo w in g week and is rec o rd ed as a mouse th a t d ied w ith a tum or p r e s e n t. W-ivl API 04784 Two o th e r mice dev elo p ed s i m il a r changes o f th e s k in by th e b eg in n in g of th e 4 4 th week and, a s in d ic a te d in th e g rap h , d ie d w ith in one o r more weeks t h e r e a f t e r . The b lack blocks d e sig n ate mice th a t died w ithout showing tum ors, but a t a tim e when cutaneous o u tg ro w th s were a p p a re n t in some o th e r mice of th e group. Thus both th e and the black blocks denote mice th a t d ied w ith o u t any tum ors p re se n t on visual inspection. The a p p a re n t p ro d u c tio n o f tum ors by w h ite o i l was n o t confirm ed when s e c tio n s o f th e su g g e stiv e a re a s o f sk in were examined m ic r o s c o p ic a lly . The ex am in a tio n o f one o f th e tum ors, b elieved to have developed in the 43rd week, revealed only a sm all area o f desquam ating e p ith eliu m , the base of which showed c e l lu l a r i n f i l t r a t i o n and v a s c u la r c o n g e stio n , and the m argins o f which showed a c a n th o s is and p a r a k e r a to s is . S e c tio n s of th e a ff e c te d a re a o f th e sk in o f a n o th e r mouse showed only a patchy h y p e rk e ra to sis and one sm all a re a o f a ca n th o sis of the ep ith eliu m , to g e th e r w ith congestion o f the dermal v e sse ls, and s l i g h t edema and c e l l u l a r inflam m atory r e a c tio n o f th e derm is. Another mouse, which had developed a su sp icio u s a re a on th e s k in by th e b e g in n in g o f th e 3 8 th week, was n o t examined post-m ortem . Of th e o th e r 17 mice in t h i s group, V 0 - 10 - a l l of which died w ithout any apparent sign of a tumor, 3 were not examined a f t e r d e a th , and the sk in o f 2 o th e rs ap p eared so n e a r ly norm al t h a t s e c tio n s were n o t made o f i t . M icroscopic e x am in a tio n o f th e s k in of th e rem aining 12 mice re v e a le d n o th in g abnorm al in , e v id e n ce o f c h ro n ic inflam m a tio n in 2, patchy h y p e rk e ra to sis in 1, and a s lig h t degree of acanthosis in 1. These observations in d ic a te th a t co ntact w ith w hite o i l did n o t induce a cutaneous m alignant tumor in any one of 20 m ice, a lth o u g h t h i s o i l cannot be reg ard ed as e n ti r e l y innocuous, since chronic inflam m atory and o th er changes ap peared in the sk in of 6 o f th e 20 m ice, and in 3 o f them were of such a ch aracter as to have caused the a ffe cte d areas to be re c o rd e d a s tum ors d u rin g l i f e . M ethylcholanthrene in White M ineral O il T his c o n tro l group was included in order to t e s t the b eh av io r o f a known a c tiv e c a rc in o g e n in a s o lv e n t c lo s e ly r e la te d to th e o i l s to be te s te d . U n fo rtu n ate ly , 20-m ethylch o lan th ren e was found to be only s l i g h t l y so lu b le in w hite m ineral o i l . A s a tu ra te d s o lu tio n was employed. I t s con c e n tra tio n was n o t d eterm in ed , b u t in a l l lik e lih o o d , i t was considerably le s s than 0.3 per cen t. API 04786 - 11 - Only 7 o f th e 20 mice d ie d w ith o u t h av in g d eveloped a cutaneous le s io n re c o rd e d a s a tumor d u rin g l i f e . The f i r s t tumor was re c o rd e d a t th e b e g in n in g o f th e 2 7th week. Mi croscopic exam ination revealed the presence of squam ous-cell carcinom as in 3 o f th e 13 mice re c o rd e d a s h av in g tum ors. S ections o f th e tum ors of 9 of them have n o t y e t been examined, and th e rem ain in g mouse was n o t exam ined a f t e r d e a th . No v i s c e r a l m e ta s ta s e s were found. One o f th e 7 mice w ith o u t tumors was not examined a f t e r d e a th , and s e c tio n s of th e sk in of 2 showed no m alig n an t tum ors b u t such changes as s l i g h t d y sk e ra to sis, moderate to severe h y p e rk e rato sis and moderate a c a n th o s is . One showed an i r r i t a t i v e d e rm a to s is . I t may be concluded t h a t a s o lu tio n o f 2 0 -m eth y lc h o lan threne in white m ineral o il ex h ib ited d e fin ite evidence of i t s a b i l i t y to a c t a s a c arc in o g e n ic agent in mice o f the C^H s tr a in * 0.3 Per Cent M ethylcholanthrene in Benzene T his group was designed as a p o sitiv e c o n tro l. (Benzene, was th e s o lv e n t employed by the E n g lis h w o rk ers in d e te rm in in g th e carcinogenic a c tiv ity of a la rg e number of p o ly cy c lic arom atic compounds, the co n ce n tra tio n being 0.3 per cent in API 04787 most in s ta n c e s . ) A ll but 4 mice e x h ib ite d one or more tum ors a t th e time o f d e a th . The f i r s t tumor was e v id e n t a t th e beginning of the 23rd week and the l a s t had appeared by th e 40th week. M icroscopic exam ination of th e tum ors borne by 4 of th e m ice, which may be reg ard ed as r e p r e s e n ta tiv e of th e group as a whole, showed th a t each was a squam ous-cell c a r cinoma, u s u a lly o f Grade I I I or IV (Broders* c l a s s i f i c a t i o n ) . The tumor had m e ta s ta s iz e d to th e lungs o f one mouse, but no v is c e ra l o r a x illa r y m tastass were observed in any of the o th er 15 mice w ith tum ors. 0.6 Per Cent M ethylcholanthrene in Benzene Of th e 20 mice in t h i s group, 2 d ie d d u rin g th e 5th week. A ll o f th e o th e rs developed le s io n s re p o rte d a s tum ors, which made t h e i r appearance between th e 12th and 24th weeks. In some in s ta n c e s , th e y a tt a i n e d a d ia m e te r o f 2.5 cm. The chief e ffe c t of doubling the concentration was, th e re fo re , to decrease th e l a t e n t p erio d b efo re tumors became e v id e n t. Ten o f th e 18 outgrow ths were examined m ic ro s c o p ic a lly . With the ex cep tio n of 1 mouse, which had only a few c o rn ified elev atio n s of th e size of a pin head, ch aracterized micro sc o p ic a lly by m oderate h y p e rk e ra to sis w ith a patchy a c a n th o tic API 04788 T - 13 - re a c tio n , a l l of th e o th e rs were found to be ty p ic a l squamous c e ll carcinomas containing a ty p ic a l, often b in u clear c e lls , many m ito tic f i g u r e s , and showing v a r i a b le d e g re e s o f p e a r l fo rm a tio n . In many c a s e s , th e r e was in v a s io n of th e su p e r f i c i a l l y p laced s k e l e t a l m uscle. M e ta s ta sis occu rred in an a x i l l a r y node o f one mouse and in th e lu n g s of a n o th e r. Very s im ila r r e s u lts were o b tain ed in a r e p e titio n of th e ex p erim en t w ith a group o f 17 male mice of th e GFW s t r a i n . The C arcin o g en ic P r o p e r tie s o f 5 O ils O il W-3632 S ix o f th e 20 mice in t h i s group d ie d w ith o u t hav ig a ffo rd e d any e v id e n c e of tum or fo rm a tio n . Two o th e r s re p o rte d as bearing sm all tumors died during the 3 0 th and 31st weeks, re sp e c tiv e ly , but m icroscopic exam ination of th e ir skin re vealed only the presence of h y p erk erato sis and acan th o sis. Two mice had u n q u e s tio n a b le tu m o rs, (one w eighed 3 .5 g . ) which were n o t examined m ic r o s c o p ic a lly . The tum ors borne other by th e /1 0 mice were a l l sq u a m o v s-ce lle d c arcin o m as. The gross and m icroscopic o b se rv atio n s on each of th e mice of th is group are given in Table U A r e p e t i t i o n o f th e t e s t o f t h i s o i l , u sin g CFW m ice, is n e a rin g c o m p le tio n . S ince some o f th e m ice a re s t i l l API 04789 ) - 14 - liv in g , the data have not been incorporated in the graph, | but i t is ap p aren t t h a t th e outcome w ill not d i f f e r g r e a tly from t h a t d e s c rib e d in th e case of th e C^H m ice. O il W-3631 F ive o f the mice of t h is group e x h ib ite d very sm all localized areas of thickening or in cru sta tio n of the skin, which were rec o rd ed a s tum ors on th e g ra p h . The f i r s t o f <1 th e s e was n o ted a t th e b e g in n in g of th e 3 0 th week, b u t th e o th e r s ap p eared much l a t e r (4# to 55 w eek s). One o f th e s e fiv e mice was not examined p o st mortem. Exam ination o f a s e c tio n o f th e s k in o f a n o th e r member o f t h i s group r e vealed a sm all area of m alignant neoplasia of the skin (squamous c e lls ) in r e l a ti o n to a v erru co u s h y p e rk e ra to tic le s io n , the g re a te r p a rt of which was n e c ro tic . There were numerous in tra d e rm a l k e ra to -h y a lin e c y sts in the a d ja ce n t I s k in . The tumor was c la s s e d a s b e in g o f Grade I in m a lig nancy (B roders' c la s s if ic a tio n ) . A second se c tio n of th is tumor d isp la y e d only v e rru co u s h y p e rp la sia w ith hy p erk era to s is . S e c tio n s of th e sk in of th e o th e r 3 mice th a t had been rep o rte d as bearing tumors during l i f e e x h ib ite d only moderate o r s lig h t h y p e rk e ra to sis and s lig h t a c a n th o sis. I t is b e liev ed th a t th e changes observed d uring l i f e were API 04790 V 15 - re la te d to areas of hyperkeratosis w ith the form ation of kerato-hyaline plugs in the e p ith e lia l cry p ts. Sim ilar changes were observed m icro sco p ically in the skin of 6 of th e mice th a t f a ile d to arouse su sp ic io n o f tumor form ation d u rin g l i f e . This o i l m ust be reg ard ed as inducing an i r r i t a t i v e d e rm a to sis, and in th e case of 1 of th e 20 m ice, a tum or of a low -grade o f m alignancy d e v el oped. O il W-3630 None of th e 20 mice o f t h i s group gave any ev id en ce of tumor form ation during l i f e . N ecropsies were not p er formed on 6 o f th e s e mice and no s e c t i o n o f th e a p p a re n tly u n a lte r e d s k in was ta k e n on two o t h e r s . No evid en ce of m alig n ant change was found on exam in atio n o f s e c tio n s o f the s k in o f 12 o f th e m ic e , a lth o u g h v e ry s l i g h t h yper k e ra to s is was n o ted in th o se o f 4 , and s lig h t d y s k e ra to sis in th o se o f 2. In a d d itio n to h y p e rk e ra to s is , one showed an a re a o f v e rru c o u s p r o l i f e r a t i o n . No a b n o rm a litie s were no ted in any of th e o th e r s . Oil N-5295-2 Only one o f th e mice o f t h i s group e x h ib ite d any API 04791 ) - 16 - cutaneous abnorm ality during l i f e . A la rg e dark red spot which ap p eared on th e back o f t h i s an im al became an open lesion that fa ile d to heal during the progress of the experim ent, b u t, as th e re was no a p p a re n t ou tg ro w th , i t was not recorded on the graph as a tum or. However, m icroscopic exam ination of th e skin revealed h y p erk erato sis w ith a large area o f pyoderm ia. In a d d itio n , th e re was a la rg e sub e p ith e lia l tumor composed of c lo se ly packed c e lls extending to and in v o lv in g the muscle la y e r. These c e lls were oval or sp in d le -s h a p e d and p o sse sse d h y p e rc h ro m atic n u c l e i . The tumor ap p aren tly aro se in an inflam ed d y s k e ra to tic su rfa c e area and undermined th e surrounding r e la tiv e ly normal e p ith e lium. I t was concluded th a t t h i s was a pleom orphic squamous c e ll carcinoma o f grade I I I . Skin s e c tio n s of 10 o th e r mice rev e ale d no m alig n an t changes, alth o u g h 7 showed s l i g h t to moderate h y p e rk e ra to sis and 3 showed a c a n th o s is , which in one case was noted in th e su rface ep ith eliu m and in th a t of the hair f o llic le s and sh a fts. O il N-8295-3 None o f th e s e mice d ev elo p ed any tum ors d u rin g l i f e . Their absence was confirm ed by m icroscopic exam ination of sectio n s of th e sk in o f 14, one of which gave evidence o f an API 04792 i r r i t a t i v e d e rm a to s is . Two showed d e f i n i t e v e rru c o u s p a p i l l o mas, and s e v e ra l o th e rs v a ry in g d e g re es of h y p e rk e ra to s is , dyskeratosis and acan th o sis. n i l 11396 No m alig n an t tum ors were o b serv ed d u rin g th e l i f e of any of th e mice of t h i s group and no evidence of m alignant change was found on m icro sco p ic exam in atio n of s e c tio n s of th e sk in of li*. of th e s e m ice. One showed v e rru c o u s h y p e rk e ra to sis and a moderate degree of a c a n th o sis, b u t, in g en eral, changes of t h i s n a tu re were s lig h t ana in fre q u e n tly encountered. O il 11385 No tum or fo rm a tio n was n o te d d u rin g l i f e in any o f th e 20 mice and no m alig n an t tum ors were found on m ic ro sc o p ic ex am ination o f s k in from 11 of th e s e m ice, a lth o u g h 2 of them showed v e rru co u s p a p illo m a ta w ith w ell-m arked h y p e rk e ra to s is and a ca n th o sis. O il 11980 D uring l i f e no ev id e n ce o f tu m o r-fo rm a tio n was n o te d , but w ell-m arked h isto p a th o lo g ic changes were noted in skin of most of th e 1$ an im als s u b je c te d to m icro sco p ic ex am in a tio n . In one in s ta n c e , th e changes were such as to a ffo rd m oderate API 04793 -- 18 - evidence of m alignant a lte r a tio n , and, in an o th er, they represented a close approach to m alignancy. Verrucous hyper k e ra to s is and a c a n th o s is were noted in 8 in s ta n c e s , and in 5 these changes were lo c a liz e d in papillom atous a re a s , one of them ped u n cu lated . In s e v e ra l s e c t i o n s , fo c a l c o lle c tio n s of ta rry o i l were noted in th e derm is. DISCUSSION Not one o f th ese 8 o ils f a ile d to a ff e c t the skin in some m anner. O ils W-3 6 3 O and 11896 gave th e l e a s t ev id en ce of an i r r i t a t i v e a c tio n . O ils 11885 and N-8295-3 produced a few verrucous p a p illo m a ta . O il 11980 gave r is e to se v e ra l papillom atous a re a s, and in 2 of the anim als painted w ith i t th e changes were on th e b o rd e r l i n e o f m alig n an cy . One m alig n an t grow th was fo u n d in each o f th e two. groups of 20 painted w ith O ils 3631 and N-8295-2, re s p e c tiv e ly . O il 3632 u was h ig h ly c a rc in o g e n ic , b ein g about as a c tiv e in t h i s re s p e c t as a 0.3 per cent so lu tio n of 20-m ethylcholanthrene in benzene. In i t s carcinogenic a c tiv ity , i t fa r exceeds any of the other o ils tested. In 1925, Kennaway ( B r i ti s h M edical J o u rn a l 2, 1(1925) ) showed t h a t a sample o f C a lif o r n ia crude petroleum which f a i l e d to produce a tumor in any one of 100 m ice, acq u ired carcinogenic API 04794 \ ) - 19 - p r o p e r tie s when p assed a t a r a t e o f 12 to 15 m l. p er hour over a porous p la te k ep t a t 330 in an atm osphere o f hydrogen. Our most p o te n t O il W-3932 had been s u b je c te d to a r e a c t i o n tem perature of 1000F., and about 40 per cen t of i t d i s t i l l e d between 688 and 760F. O il 3631, which produced one tum or, had been su b jected to therm al cracking a t a c o il o u tle t tem p eratu re o f 940F. In th e absence o f more d e ta ile d inform a " t io n on th e o p e ra tin g te m p e ra tu re s t o which th e o th e r o i l s had been s u b je c te d , no f u r t h e r a p p r a i s a l can be made o f th e e ffe c t of high tem peratures in form ing carcinogenic hydro carbons. The c o n tr o l e x p e rim e n ts w ith m e th y lc h o la n th re n e suggest th a t the g re a te r the concentration of the carcinogenic hydrocarbon, the e a r lie r w ill cancers appear. There i s , indeed, a su rp risin g uniform ity in the tim e of appearance of the tum ors in groups o f C^H and CFW m ice, p a in te d w ith a 0.6 per c e n t s o lu tio n o f m eth y lch o lan th ren e in benzene. The graph in c lu d e s th e r e s u l t s of an experim ent perform ed in England in which mice o f an u n d esig n ated s tr a in were p a in te d tw ice p er week w ith a 0 ,3 p e r cen t s o l u t i o n . The in c id e n c e of tum ors i s v e ry s im ila r to t h a t w hich we o b serv ed in th e case of mice p a in te d once per week w ith a 0 .6 p er c e n t s o lu tio n . API 04795 ) - 20 - However, f u r th e r r e p e titio n s of th e se experim ents are necessary in order to e sta b lish the degree of reproauc ib ility of the re s u lts . A ttem p ts a re now b e in g made to d e v e lo p a m ethod o f p lo ttin g th e d ata so a s to perm it th e n u m erical c h a r a c te r iz a t io n o f the p oten cy o f an o i l or o f a s o lu tio n o f a c a r c in o g e n . Such a n u m e r ic a l c h a r a c t e r iz a t io n may be o f great valu e in any system ic approach to the stu dy o f th e in flu e n c e o f v a rio u s fa c to r s in co n ferrin g ca rcin o g en ic . p o te n c y upon p e t r o le u m - p r o d u c t s . I t may a l s o be o f u s e in le a r n in g more e x a c t ly th e e f f e c t s o f p r o g r e s s iv e d i lu t i o n o f an a c t iv e p rod u ct upon i t s p o te n c y . . From th e K e tte r in g L a b o ra to ry o f A p p lie d P h y s io lo g y , C o lleg e o f M ed icin e, U n iv e r s ity o f C in c in n a ti, C in c in n a ti, O hio. E x p e r im e n ta l Work b y: Wm. B . D e ic h m a n n , P h .D . B a th o lo g ic O b servation s by: K. V . K i t z m i l l e r , M .D. Report by: F r a n c is F . H e y r o th , M .D. D ate N ovem ber 5 . 19A&. R obert A. Keho, D irector M. D . API 04796 ) 80 0 IO WEEKS API 04797  P i Me^ai >ft Cept f'le No-. API 04798 API 04799 Id e n tific a tio n Number W -3632 W -3631 W -3630 ' N *8295-2 N -e2 9 5 -3 ! No. 11896 ! No. 11885 1 No. 11980 T able 1 L ab els Borne By the E igh t O ils ' Company S h e ll O il Company, W ilm in gton , C a lifo r n ia S h e ll O il C<*npany, W ilm in g to n , C a lif o r n ia S h e ll O il Company, W ilm in gton, C a lifo r n ia U nion O il Company o f C a lif o r n ia , W ilm in gton , C a lifo r n ia U nion O il Company o f C a lif o r n ia , W ilm in gton , C a lifo r n ia G en eral P etroleum C o rp o ra tio n , P rocess L ab oratory, Los A n g eles, C a lifo r n ia G eneral P etroleum C orp oration , P rocess L ab oratory, Los A n geles, C a lifo r n ia , G eneral P etroleum C orp oration Remarks on L abel or In L e tte r F lu id C at, C la r ifie d O il, C at. U n flash ed Th. R esidue U n trea ted C at. Gas O il TCC T a r s Thermo R e c y c le S t r a ig h t Run Gas O il from W ilm ington S t r a ig h t Run R e s id u a l from W ilm ington TCC R e c y c l e S t o c k (fr o m T o r r a n c e TCC U n i t T 4 , o p era tin g w ith a 2 4 -fo o t bed o f bead c a t a ly s t on a ch a rg e o f irixed s t r a ig h t run g a s o i l from C a lifo r n ia H igh Pour and W ilm ington C rudes) ) Table 2 A n a ly tic a l D ata on Three of th e O lla Id e n tific a tio n N u m b e r ______ W -3632 W -3631 W -3630 ' N*e295-2 N-e295-3 No. 11896 No. 11885 No. 11980 T able 1 L ab els Borne By the E ig h t O ils Company S h e ll O il Company, W ilm in g to n , C a lifo r n ia S h e ll O il Company, W ilm in gton , C a lifo r n ia S h e ll O il Company, W ilm in gton , C a lifo r n ia U n ion O il Company o f C a l i f o r n i a , W ilm in gton, C a lifo r n ia U n ion O il Company o f C a l i f o r n i a , W ilm in gton, C a lifo r n ia G en era l P etroleum C o rp o ra tio n , P ro cess L ab oratory, Los A n g e le s, C a lifo r n ia G en eral P etroleum C o rp o ra tio n , P rocess L aboratory, Los A n g eles, C a lifo r n ia , G en eral P etroleum C o rp o ra tio n Remarks on L ab el o r In L e tte r F lu id C at, C la r ifie d O il, C at. U n flash ed Th. R esid u e U n treated C a t. Gas O il TCC T a r s Thermo R e c y c le S t r a ig h t Run Gas O il from W ilm ington S t r a ig h t Run R e s id u a l from ^ Wi lin in g t o n TCC R e c y c l e S t o c k (fr o m T o r r a n c e TCC U n i t T 4 , A n a ly tic a l D ata on W hite M in eral O il S pecific G ravity at 60 F. .8 6 0 M in. C o lo r, Sayb olt + 30 Up V is c o s ity , Say. n iv. a t 100 F . 85 F lash , Pensky-M artens C losed , 0 F. 330 Pour P o in t, F. Copper T est, 2 h r. at 212 F. Odor T aste l A cit T est (U .S .P . T est fo r C arb on lzab le Subs tane es ) U .S .P . Cloud Must Pass U .S .P . A c id ity T est Must Pass U .S .P . S u lfu r Compounds Peroxide S t a b ilit y a t 300 F ., m in u tes Mus t Pas s 20* S u n lig h t P ero x id e S t a b i li t y ( S - l Lamp), h r s . 3* S u n lig h t Odor, m inutes 5* Mercury Index .8 7 0 Max. 95 0 5 2 2 2* 2* * D esired but not guaranteed. API 04801 ) ) Table 4 G ross and M icroscopic O b se rv a tio n s on th e Skin of Mice S u b je c te d to C u t a n e o u s (TonP a c t W i t h ClI~W ^7g32 4 Number of Mouse 3 e r l a l Number o f Week I n Which a Tumor Appeared 5400 29 5401 31 5402 27 5403 19 S e r i a l Number o f Week I n W hich The Mouse Died 35 Gross O bservations 3 to 4 elevated areas of in c ru sta tio n , m easuring 1 x 1 o r 1 x 2 mm. 46 Tumor m ass, w e ig h in g 8.5 g. and m easuring 3 x 2 .5 x 2 cm. 28 No n e c r o p s y 26 U lc e r a te d tum or, 1 cm. In h eig h t and 1.2 x 0.8 cm. In a r e a . Not f ix e d to underlying fa s c ia l. M icrosoopio Obaervatlons ? N eo p lastic p r o lif e r a tio n o f squamous epithelium associated w ith extensive pyogenic Inflam m ation, h y p e rk e ra to sis, acanthosis. No s e c t i o n E p ith e lia l tumor composed of a n a p la s tic squamous c e lls w ith v e s ic u la r , hyperchrom atic n u c le ic and fre q u e n t m ito tic f ig u r e s , growing In Irre g u la r sheets and trab ecu lae and ex te n d in g I n t o th e c o rlu m . Much k r a t i n i s a tio n and p earl form ation. S u p e rfic ia l u lo eratlo n . A djacent epithelium hyperkerato tlo and ao an th o tlc w ith larg e areas of n e c r o s i s . No v i s c e r a l m t a s t a s s . 5404 29 5405 31 41 Tumor, 3 x 5 x 16 mm. S quam ous-cell carcinom a o f s k in w ith much k ra tin is a tio n . A la rg e p o rtio n of the tuipor has undergone d e g e n e ra tio n and n ecro sis w ith asso ciated pyogenic lnflantna- t o r y r e a c t i o n . No m t a s t a s s . 48 Tumor, 3 . 5 x 2 . 5 x 2 cm. Bulky verrucous tumor w ith w idespread m alignant squamouncell n e o p la sia . D lagnosls- Squam ous-cell carcinom a o f Grade I I . API 04802 ) * T able 4 (Page 2) Number of Mouse 5406 3 e r l a l Number o f Week I n Which a Tumor Appeared S e r i a l Number o f Week I n Which th e Mouse Died 32 5407 34 42 5408 21 32 Gross O bservations M icroscopic O bservations I n c r u s t a t i o n , 1 mm, in diam eter H yperkeratosis and s lig h t a c a n th o sis. No t u m o r . C o rn lfle d a re a , 10 x 1 0 x 2 mm. Pronounced hyp erk erato sis, acan th o sis, h y p erk eratin lzatlo n w ith p earl form ation, asso ciated w ith w ell-defined m alignant tum or o f squam ous e p i t h e l i u m . Many l a r g e g ia n t n u c le i, numerous b ln u c le a te d c e l l s , hyperchrom atism . Large area of d eg en eratio n and n e c ro sis. Biopsy In 26th week. At Death: 31te of a p p l i c a t i o n on back covered w ith loose sloughing n ecro tic ep ith elial tissue, m atted h a ir , and d rie d blood. Odor characteristic of m oist necrotic tissu e . Skin scar a t s ite of previous biopsy! Sloughing tissu e r e moved exposing discrete finely fungoid g listen in g g ra y tumor (15 x 10 x 4 mm.), under s u r f a c e o f s k i n . One t i n y n o d u le (4 mm.) probably sm all tumor by d ir e c t ex ten sio n . An u l c e r a t e d p a p i l l o m a t o u s s q u a m o u s - c e l l carcinom a invading and d estroying the most s u p e r f ic ia l lamina of s t r a t i f i e d m uscle. The tumor is composed of a ty p ic a l la r g e k eratin ized c e lls w ith large v esicu lar n u clei; m ito tic fig u re s, m ostly a ty p ic a l, a r e f a i r l y common and b l n u c l e a t e d c e l l s a r e num erous; th e re I s edema and I n f i l t r a t i o n of the u n d e rly in g co n n ectiv e tis s u e by la rg e m ononuclear c e l l s , lymphocytes and a few polym orphonuclear c e lls . S e c tio n removed a f t e r death: Squam ous-cell c a r c in o m a o f s k i n , rfo m e E a s ta s e s i n lym ph nodes or v iscera. API 04803 Table 4 (Page 3) Number* of Mouse 5409 Seri e l Number of Week In Which Tumor Appeared 30 S e r i a l Number o f Week i n Which the Mouse Died 36 5440 26 38 5441 26 36 5442 38 5443 16 Gross O bservations M icroscopic O bservations Very sm all tumor (0.5 cm.) w ith c ru stin g of epiderm is C o m ifio d e p i t h e l i a l tumor 10 x 6 x 3 mm. D a rk brown and very h a rd . Squamous-cell carcinoma of sk in . M alignant tumor o f squam ous-cell o r ig in . Skin surface h y p erk erato tic w ith extensive pyogenic in fla m m a tio n . Numerous tumor g ia n t c e lls with hyperchrom atic n u c le i. Tumor o f i n t e r s c a p u l a r area (3 x 2 .5 x 1 .5 cm .), brownish d is c o lo ra tio n ,, thickened crusted epiderm is, patchy loss of h a i r . S e c tio n of tumor perm its the escape of a la rg e amount of whey lik e f lu id and sm all particles of tissue. C ortex of tumor is ir r e g u la r and g lis te n in g . Gray w hite c u t su rfa c e . No i n v o l v e m e n t o f s u b j a cent m uscle. Bulky, squam ous-cell carcinom a w ith a g re a t d e a l of k e r a tin iz a tlo n and p e a rl fornnetion. S urface of tumor covered w i t h h y p e r k e r a t o t i c e p i t h e l i u m . No m tastass. A xillary nodes not rem arkable. Crusted area of 3 x 4 mm. w i t h o n e b r o w n i s h , circum scribed elevation l x l x l mm. Pronounced a c a n th o sis and h y p e rk e ra to sis w ithout d e fin ite evidence of m alignant change. No n e c r o p s y . 04804 4 Table 4 (Page 4) Number o f House 5444 S e r i a l Number o f Week I n Which Tumor Appeared S e r i a l Number o f Week i n Which the Mouse Died 28 5445 16 5446 12 5447 30 32 Gross Observations No e v i d e n c e o f tum or-like growth. No tu m o r No n e c r o p s y Crusted area, 1 x 2 x 2 mm. 5448 5449 29 No tu m o r . 34 No tu m o r 1 M icroscopic O bservations Skin se c tio n not rem arkable. No c u t a n e o u s o r v i s c e r a l t u m o r . A canthosis, hyperkeratosis, w ith area of neoplastic pro liferatio n of atypical squamous e p i t h e l i u m w i t h some p e n e t r a t i o n o f d e r m a . No v i s c e r a l m t a s t a s s . Skin sectio n not rem arkable. API 04805 d 3 Wri * Hco Jd 2 ' MIETS SUBCOMMITTEE OH CARCINOGENICITT November 11, 19^9 A semi-annual meeting o f the Subcommitee on C arcinogenicity was con vened a t 11:00 A.M. Thursday, November 11, 19^8, In P riv ate Lining Boom #1 of the Stevens H otel, Chicago. (BUBERS PBSSEHT L.X. C urtis T.M. Frank A.E. Hoag J J . Holt V.R. Levis M.H. Newquist C.A. Swan Mclver Woody L.C. Beard, J r A.E. Dooley H.O.M. 71eeher H.B. Warrick H.H. Zuldema VISITORS V.C. B aird W.V. Brooks 7 .F. Boys E ie ffe r Davis BtB. Reeves E.W. Adams R.C. Cole N .J. Gothard QUESTS Dr. Robert A. Eehoe - U n iv ersity o f C incinnati Dr. S ta n d s P. Heyroth - " " " Dr. A. Wesley Horton - " " Dr. V.D. S eyfried - Humble Oil !t R efining Company Dr. S.S. Shaffer - * "" " " Dr. H.W. Stevenson - S hell Petroleum Company, L td ., London Dr. W.J. Sweeney - Standard O il Development Con?any T otal in Attendance - 28 MEMBERS ABSENT T .J. Kelly R.S. Bonsib A .J. loewlng, J r . H.P. Lankelma API 04806 The new members and g u e sts, L .F . C u rtis, C.A. Swan, R.A. Kehoe, fra n c is F. Eeyroth, A.W. Horton, W.D. Seyfried, S.S. S h affer, H.W. Stevenson, W.J* Sweeney were introduced. Dr. Kehoe re p o rte d on the s ta tu s of the experim ental stu d ies a t the fe tte rin g laboratory and pointed out the d e s ira b ility of! 1 - F a c ilitie s adequate to se le c t m aterials needed to be te sted . 2 - Means whereby samples could be stu d ied as to th e ir r e la tiv e p o te n cies. 2 - Systematic d ata on the incidence o f malignancy in petroleum workers exposed to these m aterials. As to th e 'p ro g re ss of the b u ild in g program a t C in cin n ati, he sa id th a t the new wing o rig in a lly scheduled fo r completion in May 19^3 would su rely be ready fo r occupancy by March 19^9 and would include a sp e c ia l animal house on the roof, which has been designed fo r mice and o th e r sm all animals which are used in cancer s tu d ie s. He reminded us th a t th is a d d itio n a l space and the equipment to he in s ta lle d th e re in was made p o ssib le by the re c en t A .P .I. g ra n t fo r c a p ita l expense and he assured us th a t th is space, or i t s equivalent elsewhere in the building, would be reserved fo r our work. Dr. A. Wesley Horton, who has ju s t been appointed as A ssista n t P ro fesso r of In d u s tria l Hygiene, was introduced by Dr. Eeyroth, who explained th a t h is entire time would be devoted to our problem. In making th is appointment, they have sele c ted an organic chemist with p r a c tic a l experience in p o ly cy clic compounds, a knowledge of p h y sica l chem istry and an understanding of our in d u s tria l problems and tech n ical p ro c e sses. Dr. Kehoe sa id th a t th e ir new P ro fesso r of Preventive Medicine, who is one of the three outstanding epidem iologists in the country, w ill be able to devote h a lf h is time to the A .P .I. p ro je c t during the coming y e a r. Dr. Eeyroth then re p o rte d on the r e s u lts o f te s t s of the eig h t A .P .I. samples. His re p o rt and c h arts w ill be reproduced and d is trib u te d to members of the Committee. Dr. E olt recommended th a t a wider range of samples be stu d ie d , e sp e c ia lly those in the hig h er b o ilin g ranges (above 700 F) and th a t waxes be in v estig ate d also, Ee c ite d an a r t i c l e in the N.Y. Times of November 7, 19^8 and s a id th a t Standard O il (N .J.) w ill cooperate fu lly w ith the U.S. Public Health Service in its a c tiv itie s in th is f ie ld . Jersey has found th a t, i f the heavy o il is d ilu ted with 71$ white m ineral o i l , the a c tiv ity is reduced to about one-fourth i t s original potency. Dr. Newquist re fe rre d to recen t statem ents in the lit e r a t u r e which say that any skin tumor should be considered as p o te n tia lly m alignant. Dr. Frank thought i t would be d e sira b le to study the e f f e c ts of these oils following repeated ap p licatio n s and washings, thus sim ulating the actu al exposure o f employees. -2API 04807 % n Dr. Hoag re a d a re p o rt p rep ared by the M etropolitan L ife Insurance Company on "S t a t i s t i c s on Cancer Among Workers In the O il In d u stry " . He a lso suggested th a t some ways he found to challenge in c o rre c t newspaper a r t i c l e s ; f 0T example, a re c e n t statem ent r e f e r r in g to p a r a f f in wax as being carcin o g e n ic . Dr. Beard read a l e t t e r from Col. Auld of the I n s titu te of Petroleum (England) and suggested th a t C ol. Auld he in v ite d to a tte n d a fu tu re meeting of the Medical Advisory Committee and d escrib e the work being done In England. Dr. Stevenson explained th a t any inform ation given C ol. Auld on the problem in the U nited S ta te s would be con sid ered c o n fid e n tia l; th a t the I n s titu te 0f Petroleum was s im ila r to the A .P .I. Ij ' Mr. W arrick s tr e s s e d the d e s i r a b i l i t y o f fin d in g out more about the formation of carcinogens and urged th a t the tech n ical advisers meet soon with pr. Horton to discuss these m atters. Mr. Zuidema asked th a t a comparison between c a ta ly tic cracked and thermal cracked m a te ria l be made. Dr. Kehoe and Dr. H eyroth, in d iscu ssin g fu tu re work, advocated: X- Careful consideration in se le c tin g samples fo r future te s tin g , taking in to account the s'ource, the nature of the crude, the tenroerature conditions, e tc . This should be considered by Dr. Horton and the technical advisers. 2 - The c o lle c tio n o f epidem iological d a ta by an e x p ert in th a t f i e l d . While la b o ra to ry methods can determ ine the r e la tiv e c a rc in o g e n ic ity of v ario u s m a te ria ls , the f i n a l answer w ill depend on human experience. 3 - Study of the re p ro d u c ib ility of r e s u lts and the e ffe c ts o f d ilu tio n . The follo w in g re p o rt to the M edical Advisory Committee was approved: On b e h alf o f the Subcommittee on C arcin o g e n ic ity , I p re s e n t to the Medical Advisory Committee fo r tr a n s m itta l to the S afety Committee of th e Board of D irectors and fo r adoption by the Executive Committee of the B o a rd o f D ire c to rs, the follow ing re p o rt and recommendations: 1 - That the s e le c tio n o f Dr. A. Wesley Horton fo r Dr. E ehoe's s ta ff is acceptable to u s. 2 - That the s e le c tio n of the epidem iologist for Dr. Eehoe's s ta ff Is acceptable to u s. 3 - That an a d d itio n a l $25,000. w ill be necessary to continue the program a t the U n iv e rsity o f C in c in n ati during 19^9 to be follow ed by another $25, 000. fo r the f i r s t s ix months of 1950. - 3- API 04808 k - That the fundamental chemical and physical studies th a t are indicated to Investigate the operational technical aspects o f th is problem may re q u ire co n sid erab ly more money than a n tic ip a te d ; and i t i s recommended th a t the te ch n ica l a d v ise rs grovto consider the problem ag ain and p re s e n t th e ir recommen d atio n s to the Subcommittee on C arcin o g en icity . 5 - That the carcinogenic program which the American Petroleum In s titu te is sponsoring a t the U niversity of C incinnati should include: (a) B iological te stin g program to determine the carcino g enicity of various samples. (b) B iological or other experim ental stu d ies fo r the purpose of developing quicker techniques fo r determining the carcinogenicity of these m aterials. (c) Experim entation d ire c ted toward defining p ro te c tiv e procedures th a t might be used to p ro te c t in d iv id u a ls who may come in c o n ta c t w ith these o i l s . (d) Epidem iological stu d ies of th is problem in the in d u stry . (e) (D eleted by the Medical Advisory Committee). (f) Investigation of so lid and sem i-solid natural petroleum co n stitu en ts such as red wax. A.Z. Dooley SECRETARY McI VER WOODY., M.D. CHAIRMAN API 04809 ^ t Stft.tlgtl.CJ on Cancer Among Workerb In t he O il In d u stry (Prepared, by the M etropolitan l i f e Insurance Company a t the req u est of Dr. Hoag and Mr. Beard) We have review ed the m o rta lity stu d ie s a v a ila b le to us and have canvassed the l i t e r a t u r e on the su b je c t o f cancer among workers In the o il in d u stry . So fa r as g en eral m o rta lity from cancer Is concerned, the evidence In d ic a tes th a t the death r a te fo r o i l workers Is probably no h ig h e r than the average, G a fa fe r's re p o rt on the occurrence o f cancer among employees of an o il re fin e ry published in P ublic H ealth Reports fo r August 2?, 1940, to which Hr. Beard r e f e r s in h is l e t t e r of May 2 6th, shows th a t the crude death r a te for the o i l workers was no h ig h e r than average. We have c a lc u la te d the exoected number of deaths among th ese o il workers ages 15 to 69, on the b a s is of death ra te s from cancer by ages p re v a ilin g among w hite males o f the g en eral copulation in the y ears 1933" 1938* The c a lc u la te d number of deaths expected for the s ix year p e rio d was 52. 6, whereas th e re were a c tu a lly only 46 d e a th s. Some inform ation I s given on cancers by s i t e In the o r ig in a l a r t i c l e . Employees of the o i l reifining company show r e l a t i v e l y more cancer of the d ig e stiv e system than occurred among the a d u lt male p o p u la tio n , w hile the p ro p o rtio n of cancers of the g e n ito -u rin a ry system is somewhat l e s s . We wrote to Dr. G afafer to see if he had a d d itio n a l inform ation fo r a more re c e n t p e rio d , b u t he advised us th at the 1940 re p o rt i s h is l a t e s t . Some y e a rs ago we looked in to the Group insurance experience in th is n a tte r. In the combined experience of s ix of the leading companies issu in g Group insurance in the U nited S ta te s and Canada from 1927-1932, the m o rta lity from a l l forms of cancer among a l l in su re d workers in the m ineral o i l in d u stry reg ard less of the ex act occupation, was 36 p e r 100,000 y ears o f l i f e exposed as a g a in st 62 p e r 100,000 among a l l o f the g e n eral occupation group in which those in the o il industry have been c la sse d . D etailed data by cause o f d eath are not given in re c e n t Intercompany Group r e p o r ts . Ordinary Department m o rta lity exp erien ce i s lim ite d so fa r as cancer among o i l workers i s con cern ed . However, w h ile we cannot c a lc u la t e the r a t i o of a c t u a l to e x p e c te d d ea th s from can cer among them, th e f a c t s p r e sen te d in the J o in t Occupation Study, 1928,* in d ic a te th at in a group o f o i l and ggs f i e l d foremen and m isc e lla n e o u s o p e r a tiv e s r e p r ese n te d by 51*000 l i f e y e a r s o f exposure, the cancer m o r ta lity was average or below average. Our I n d u s tr ia l Department experience is q u ite lim ite d , and the r e s u lts are out of lin e w ith o th e r s tu d ie s . The number of death s is so few, however, th at the r e s u lts a re not s ig n if ic a n t. In the p e rio d 1937-1939* the stan d ard ized r e la tiv e index fo r cancer among o i l re fin e r} ' w orkers, c a lc u la te d in the manne r o u tlin ed in our p a p er, "O ccupational M o rta lity Experience of Insured Wage E arners," was 120, based on 15 cancer d e ath s; the stan d a rd iz e d r e la tiv e index fo r the y ears 1922-1924 was 130, based on 13 d e a th s . There is a considerable lite r a tu r e on the occurrence of sk in cancers among workers in th e o i l in d u s try . The b e s t re p o rts o f which we have a re c o rd are l i s t e d on the accompanying s h e e t. P a r tic u la r a tte n tio n i s c a lle d to th e work by Schwartz, T ulipan and Peck. "Published by the A c tu a ria l Society of America and the A ssociation of Life Insurance Medical D irecto rs. API 04810 SELECTED BXEEBEKCES g^agensen, Cushman D. Occupational neonlastic disease. V ol. 3OT, A p ril 1931, p . 6U1. The American Jo u rn a l o f Cancer, S e lle r, Imre Occupational cancers. p. 169. The Jo u rn al of In d u s tr ia l Hygiene, May 1930, ' Henry, S.A. Occupational cutaneous cancer a ttrib u ta b le to c ertain chemicals in in d u stry . B r itis h Medical B u lle tin , Vol. Ho. 5-6, 19^7, p . 389. Haeper, V.C. O ccupational tumors and a l l i e d d is e a s e s . Publisher. 19^2. p . 896. C harles C. Thomas, P hillips, Charles The re la tio n s h ip between skin cancer and occupation in Texas! a review of 1569 v e r if ie d le s io n s occurring in 1190 p a tie n ts . Texas S ta te Jo u rn a l of M edicine. January, 19^1, p . 613. Schwartz, L ., T ulipn, L ouis, and Peck, S.M. O ccupational d ise a se s o f the sk in . Chapter XVL - Dermatoses caused by petroleum , p . 232. Lea & P ebiger, P h ila d e lp h ia 19^7 D.S. P ublic H ealth Service D isabling m o rbidity, and m o rta lity from cancer among the male employees o f an o i l r e fin in g company w ith re fe re n c e to age, s i t e , and d u ra tio n , 1933" 38, in c lu s iv e , by W illiam M. G afafer. P ublic H ealth R eports, August 23, 19^0, p . 1517. 1 EXCERPTS FROM COLONEL S. J . M. AUID'S IETTER OF AUGUST 6, 19U8 n The su b je c t o f th e r e la t io n s h ip o f petroleum to in d u str ia l carcinoma and indeed to cancer in general has developed rap id ly during th e l a s t year or so and appears t o be tak in g on an importance which may s e r io u s ly a f f e c t the nature and p r o v isio n o f m ineral o i l products and therefore warrants our c lo se a tte n tio n from th ose asp ects as w e ll as from the seriou s p a th o lo g ica l outlook which i s concerned. n During the e a r ly part o f the war th e m atter was r e la t i v e l y q u ie s c e n t, but came t o th e fr o n t again in r e sp e c t o f th e a lle g e d c a r c in o g e n ic ity o f t e x t i l e o i l s because o f fu r th e r work by Twort and the o f f i c i a l adoption o f the Twort " sa fe ty *1 form ula based on a s p e c i f i c r e - f r a c tiv ity r e la tio n sh ip . S p ecial o ils were s e t asid e by the petroleum Board in order t o perm it t h i s form ula t o be m et, but a t th e same t i n s , and p o ssib ly due to th e tra v ersin g o f the Twort work from d iffe r e n t sou rces, a movement was made to apply a t e s t in v iv o which r e la te d ca rcin o g en ic a c tiv ity to change in r e fra ctiv e in3ex of o i l s Injected in to the liv in g an im al. " Towards th e end o f 19U3 th e m atter suddenly came Into s t i l l greater prominence, v ia the M in is t r y of Labour, both in connection w ith the p r o v is io n o f mule sp in n in g lu b r ic a n ts and th e use in in c r e a sin g q u an tities of petroleum ex tra cts as replacements fo r products o f d ifferen t ty p es which were in sh o r t su p p ly , p a r t ic u la r ly rubber exten d ers and drying o il su b stitu tes. " As a r e s u lt , th e Petroleum Board, through i t s Tech n ic a l A d v isers, embarked an b io lo g ic a l work in the p a th o lo g ic a l Department o f th e U n iv e r s ity o f Birmingham f o r the ex p ress purpose o f develop in g the whole su b je c t on a r e l i a b l e b a s is o f o b se r v a tio n . Around th e same t in s d is c u s s io n s were s ta r t e d between th e v a rio u s M in is tr ie s and Government Departments concerned, rep resen ta tiv es o f the Spinner s ' O peratives (the trad es u n io n s), the M aster S p in n ers, and the Petroleum In d u stry. At th ese m eetings th e r e p r e s e n ta tiv e s o f th e O il In d u stry were Mr. J . A* O rie l o f the S h e ll Company and m y s e lf. One o f th e m atters th ereb y brought in to c o n sid er a tio n and now coming t o a head, was th e su ggested adoption o f tech n ical white o ils as t e x t ile lu b rican ts. ' At a r e c e n t m eeting the s ig n if ic a n c e o f t h i s move ment was c l o s e l y canvassed and th e petroleum R e p resen ta tiv es p oin ted out th a t w h ils t the research work su b sid ized by th e O il Industry had In successive reports indicated the b io lo g ica l in a ctiv ity of so-called tech n ic a l white o i l s , i t was necessary to express a warning th a t th e ir adoption should not be regarded as the f in a l step in e ith e r the in v e stig a tio n or the p r a c tic a l con sid eration of the occupational carcinoma concerned. Indeed, recommendation o f the adoption o f near w hite o i l s , wherever workers were su b ject to d ir e c t contact w ith petroleum products, might be m isleading and dangerous because o f th e assum ption t h a t nothing e l s e needed t o be done. API 04812 Page No.2 "Moreover, the question of su p p lie s, c o sts, e t c ., n ight render the s itu a tio n im practicable. I t might be f a r more im portant to develop the use under such conditions of s o lv e n t-tre a te d o ils of low b io lo g ic a l a c tiv ity combined w ith sp e c ia l a tte n tio n to the avoidance of o il d isp ersio n and to personal cleanliness. " With the demergence of the Petroleum Board arrange ments have been made f o r the research work, such as th a t a t Birmingham, to be continued under the supervisio n of the I n s titu te of Petroleum w ith funds bequeathed by the Petroleum Board and lik e ly to be added to as required by the in d iv id u a l O il Companies in the fu tu r e . In accepting th is resp o n si b i l i t y the i n s titu te of Petroleum appointed a sp e c ia l Research Group which has been placed under my Chairmanship and includes re p re se n ta tiv e s of the major companies and c e rta in U niversity w orkers. " W ithin the l a s t month, quite sep arately , the Medical II Research Council - a body of the h ig h e st standing and working d ir e c tly under the Privy Council on grants a llo c a te d by the Treasury, has decided to investigate fu lly the question of the carcinogenicity of petroleum Products. In t h i s connection S ir Edward Mellanby, the chairman of the Medical Research Council, has approached me as rep resen tin g th e I n s titu te of Petroleum fo r the purpose of e ffe c tin g contact and e sta b lish in g co-operation w ith the I Petroleum Industry in general and the I . p. Research Group in p a r tic u la r . From our conversations i t appears th a t such c o lla b o ratio n w ill be arranged. " I am informed th a t the Medical Research C ouncil's in te re s t in the subject has not developed from the te x tile considerations known to you but la rg e ly from observations made by the Medical O fficers of the Government Factory Department in d ic a tiv e of dangerous and f a i r l y wide spread symptoms a ris in g from th e use o f c e rta in mould o ils in Scotland and from work c a rrie d out on automatic to o l o p erativ es in the Midlands because of sim ila r or a llie d occurrences presumably a ris in g from contact of workers with cutting o ils . it The o rg an izatio n proposed by the Medical Research Council w ill be of a high standard and w ill bring in a l l the s p e c ia lis ts in a llie d spheres o f work in th e United Kingdom. I t i s intended th a t the in v estig atio n s s h a ll be la id out as a succession of long-term p ro je c ts. I t is thought probable, however, th a t th e ad hoc research work on which the I n s titu te of Petroleum Research Group i s prepared to embark may w ell f i t as a p a rtic u la r phase of the bigger in vestigation. " The petroleum In d u stry here has noted w ith g re a t in te r e s t the growing concern of the A .P .I. in the cancer problem in re la tio n ship t o d l . " I t seems, th e re fo re , of g re a t moment th a t step s should be taken to c o rre la te the work in the two c o u n tries not only to a s s i s t in the prosecution of the p athological in v e stig atio n but from the broader important p ra e tie a l outlook of the petroleum Industry in i t s relationship to health." API 04813 November 22 , 19^8 Subject: PAPER SEAS BT DR. W. C. HUEPER OH THE SUBJECT OT OCCUPATIONAL CANCER BEFORE THE APHA Dear Doctor Woody: A paper e n t it le d P reven tion and Control o f In d u e tr la l Cancer was reed by Dr. V. C. Hueper, C h ie f. Environmental Cancer S e c tio n . Cancer C ontrol Branch. la t io n a l Cancer I n s t it u t e . B ethesda. Md., before the In d u str ia l Hygiene S e c tio n and Subcommittee on M edical Care o f the American P u b lic H ealth A a e o c ia tio n . The o c c a sio n wae the 76th *wrmn1 m eeting o f the APHA and an audience estim a ted by the w r ite r a t 200 - 300 p eop le were in attendance a t Talbot H a ll. Mechanics B u ild in g . Boston. M assachusetts at 2130 P.M ., November 11, 19**8. In h is prelim inary remarks. Dr. Hueper in d ica te d that research on the e tio lo g y o f cancer in d ica te d a strong lin k between environment and cancer incidence* Recent evidence has pointed out a d e fin ite co rrela tio n be tween cancer in cid en ce and exposures to u ltr a - v io le t r a d ia tio n , a sb esto s, benzol, certa in organic am ines, p a ra ffin o i l s , as w ell as heavy petroleum d i s t i l l a t e s and d egrad ation products such as ta r e , co k es, and p it c h e s . He then d iscu ssed an id e a liz e d approach to the con trol of the problem which would in volve the fo llo w in g p o in ts: 1 ) E valu ate the c a r c in o g e n ic ity o f su sp ected compounds and m a te r ia ls through animal experim entation. 2 ) I n v e s tig a te v i t a l s t a t i s t i c s reco rd s fo r c a ses o f cancer and tra ce the eiqsloyment h isto r y o f th ese in d iv id u a ls. In c e r ta in in sta n ces i t might be necessary to employ S o c ia l S ecu rity records to fo llo w the employment o f th e in d iv id u a l. 3) In case that the foregoing provides evidence p ointing to an un usual incidence of cancer in a certain industry, the plant rec ords o f that in d u stry w i l l be in v e s tig a te d to determ ine what a c t i v i t i e s and exposures w ith in th at industry produce the higher incidences of cancer. k ) M edical d ia g n o s tic procedures must be improved as a grea t many ca ses are being m issed at the p resen t tim e. C onsiderable work of th $s type i s being done in p r iv a te la b o r a to r ie s and the D octor Woody -2- leveaber 22, 1948 Public Health Service lg sottin g up inch a laboratory at Georgetown U niversity, Washington, D. C. 5) In itia te preventive aearuree as soon as possible since the id en tifica tio n of the offending agent Is not necessary. In d u strially, the approach would be as follow s: a) Through technical control ala at tho couplets e lla in a tio n of tho exposure or, b) Minimize the exposure by seeking iproved in d u strial ap paratus such as leak-proof equipment, closed oystoas, e tc . e) Provide su itab le personal p rotective equlpaent such as glomes, boots, impervious cloth in g, e tc . d) Provide adequate sanitary f a c i l i t i e s . This would require an expansion of looker f a c i l i t i e s In aost ex istin g p lan ts. e ) Instruct tho workers in tho proper use of tho protective aeasures provided and t o l l thea why th eir cooperation le required. f ) Jor certain operations in industry the exposure nay be a ln la lsed by the use of tea a s, trained to perform th eir duties with a alniaua of exposure, and provided with sp ecial safeguards. 6) Medical control pragmas aust be se t up, not only for current diagnosis and treatment, but aiaed at follow ing the worker through out a la ten t period which aay extend for 15-20 years. 7) A governmental factory Inspection system would be set up to in sure that tho foregoing requirements are met. 8) Protection for workers in In tersta te commerce would be secured by s e t t l e up standards for containers and suitab le warning la b e ls. 9) B eglstratien and licen sin g by a government agency would be re quired for these fa cto ries handling known carcinogens. 10) Aaendlng of present State occupational disease laws to provide su itab le coapeneatlon fo r occupational cancer and to insure the Industrial control of exposures. Industrial hygienist November 2 3 , 19^4-6 D r. McI v e r Woody E sso S ta n d a rd O il Company 15 West fjls t S tre e t New Y o rk , New Y ork D ear D r. Woody: D uring a v i s i t y e ste rd a y to th e I l l i n o i s S ta te D iv is io n o f I n d u s t r i a l H y g ien e, Mr. K enneth M orse, D ir e c to r , t o l d me t h a t h i s D i v i s i o n w o u ld so o n s t a r t a n e n v ir o n m e n ta l can cer stu d y in th e s ta t e and b e g in work around A lto n , I l l i n o i s . He i n d i c a t e d t h a t t h i s s tu d y w ould in c l u d e th e o i l i n d u s t r y . xhe s tu d y i s t o be d o n e a t t h e r e q u e s t o f U .S . P ublic H ealth S erv ice and in co o p eratio n w ith th a t agency. R e p r e s e n ta tiv e o f th e T J.S .P .H .S . c o n f e r r e d w ith Mr. Morse ab o u t two weeks ago to make p la n s f o r t h i s s tu d y . Yours v ery tr u ly A lla n 2. D o o le y MEMORANDUM 1 November 11, 1948 gggjECT: RECEIPTS AND DISBURSEMENTS - API MEDICAL RESEARCH FUND ^ ntrlbutlona to Fund 1945 S o lic ita tio n 1947 S o lic ita tio n 1948 S o lic ita tio n TOTAL $28, 900.00 27, 800.00 94,300.000 $151,000.00 pHAbursementB from Fund Harvard. U niversity Toxicological Reviews (3-15"48) Cutting Oil Dermatits (11-19-47) University of C incinnati Carcinogenicity (7-1-48) Fluorine Study (11-28-47) Miscellaneous # Books fo r Committee Use TOTAL DISBURSEMENTS BALANCE ON DEPOSIT $27, 000.00 2,500.00 71, 000.00 2,500.00 57.77 29,500.00 73,500.00 57.77 103,057.77 47,942.23 Allocations and Obligations University of Cincinnati Carcinogenicity (1-1-49) Fluorine Study (11-28-48) 2 5 , 0 0 0 .0 0 2,500.00 Harvard U niversity Toxicological Studies (Aromatics and C atalysts) (?) Toxicological Reviews-(3-14-49) 10, 000.00 1 0 ,000.00 TOTAL ALLOCATIONS AND OBLIGATIONS UNALLOTED AND UNOBLIGATED BALANCE 27,500.-00 20, 000.00 47,500.00 $ 442.23 UNIVERSITY OF CINCINNATI y CINCINNATI IS. OHIO November 25, 1*48 CABLE ADDRESS: KETLAB C l4 c iN I TELEPHONE. UNIVERSITY 29^5 Mr. V. S t r o o p , American Petroleum I n s t i t u t e j West p o ta S t r e e t , Mev l o r k C i t i 2 j . D ear Mr. S t r o o p : r send you n e r e v i t h an account of the f i n a n c i a l s t a t u s of tne American : etroleum I n s t i t u t e p r o j e c t f o r tne i n v e s t i g a t i o n of cetroleum compounds as of October 1, 1*48. xou w i l l n o t e t h a t , c o in c id e n t w i t h tne c o m p a r a tiv e ly small amount oi work we nave been a b le to do, the e x p e n d itu re s have been s m a ll. She only advantage represented therein is that the balance remaining for f u r t h e r i n v e s t i g a t i v e work i s q u i t e c o n s i d e r a b l e . Cordially yours , 1AK ef Enc. S o b e r t * . Kehoe , M D . I API 04818 Wr UNIVERSITY OP CINCINNATI KETTERING LABORATORY OP APPLIED PHYSIOLOGY ACCOUNT OF THE AMERICAN PETROLEUM INSTITUTE FOR THE THIRL QUARTER OF 1948 ' (Based on P r o p o r t i o n o f Tinie A c t u a l l y S p e n t on P ro je c t) * p r a x is H eyroth jjarl K itz m ille r - C hem ical and T o x ic o lo g ic a l A ssista n c e P ath o lo g ical A ssistance I I 5 .O7 I 7 . 3O < ^CFT.LANEOUS EXPENSE T ra v e lin g Expense T rip to W hiting, In d ian a August 19th, 1948 D r. F ra n c is H eyroth ............................................. 1 3 2 .3 7 31.94 p ro p o rtio n o f S e c r e t a r i a l , L ib r a r y , J a n i t o r s , Wash B oys, D raftsm an, S h ip p in g C le rk s, Anim al C a re ta k e rs, E is to p a t h o l o g i c a l P r e p a r a t i o n ............................................................... 34.45 P ro p o rtio n o f H eat, Gas, E l e c t r i c i t y , Steam , G as, T elephone, < M a in te n a n c e , P e n s i o n s , A n n u i t i e s e t c ............................................ 35.88 Balance R em aining f o r Work i n 1948 at End of Second Q u a rte r 1948 . . apenditures 3 rd Q u a r t e r ....................... Balance Rem aining f o r Work i n 1948 . $24,496.48 234.64 24,261.84 $234.64 API 04819 I Decenter 1 , 19W Dr. Robert A. Xahoe Uhlv a r sity o f C incinnati K ettering Laboratory o f Applied C ollege o f Medicine Xden Arem e C incinnati 19, Ohio Physiology Deer Doctor Eehoe: Pursuant to r e c r in n is tlo a accepted by the I n s titu te 's Medical Advisory Ceesaitcee, a t aeetln g bald in Chicago on ioveaber 1 2 , 1913 and In accordance v lth under standing reached In le tte r s to and fron you under dates o f Oetober 28 and HoTeeiber 5 , 1917, os are enclosing cheek In the amount o f $2,500 payable to the U nlvareity o f C incinnati as contribu tion to sa ria development o f lnforaatlon on flu orin e and flu o rin e eeaqpunda. ary tru ly yours, DT8:d Xneloeure m u Wr. V U lla a X. Boyd, J r . S r . A. X. Saag and M ibars o f Medloal Advisory Cosed.ttee Ifcr. Lacey Valker API 04820 . uam tory OF AFFLIED F H Y S I0 L 0 6 Y & UNIVERSITY OF CINCINNATI C IN C IN N A T I . OHIO December 2, 1 ^ ? CABLE ADDRESS: KETLAB. CINCINNATI TELEPHONE. UNIVERSITY 26S Mr . D V. S t r c o p , American Petroleum I n s t i t u t e , 50 Vest 5'jth S t r e e t , jjev o r k Ci ty 2 j . pear Mr. S t r o o p : I herewith acknowledge with thanks re c e ip t of American Petroleum i n s t i t u t e ' s check in the amount of $2 5 j j . j u , covering expenditures to be made on b e h a l f of the f l u o r i n e i n v e s t i g a t i o n . Very t r u l y yours D r . Kehoe ef API 04821