Document 9MjwjBN3zznvRV2r2r7do5pL

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1957 DOC#: API052 DOCUMENT DESCRIPTION: Letters, Meeting Minutes, Reports, Journal Articles & Other Relevant Documents from 1957 1 9 ~ . / ESSO R e s e a r c h a n d ENGINEERING (FORMERLY STANDARD OIL DEVELOPMENT COMPANY) p. O B o x 1 2 1 . L i n d e n , n . j. COMPANY medical research R O B E S" E EC KA R O T PH division D MO DIR ECTO R N V HENDRICKS CH E HCAO IND U STR IA L H V O IIN IS T H O RA C E W S E R A R D E PH O M D m ia o t o x ic o l o o ist BERTRAND E BENNlSON. M D C H IEF CLINICAL R E S E A R C H RHVSICIAN h m m r T, i m ** klitanl m !, c m J L s e. ***** API 06275 1 pataaa, January 7 1957 - 2 - to at, frs roviwlac tide >io ad it ia certainlj q la erigili until dafiaitely ; belief that canear of the oil# or otme eLnaral ella in the to m u r i * of III eil fina gettlhg ee e a de te help jee nth cattine oil* of the la sf the akin, bp the inetitotlan API 06276 f Ksso KhSEAHCH AND EN<JINEKI<IN<1 tPOMMSMLY S T A t D A U B OIL DKVKLOPMKNT C O M PA N Y , P (I B o a 12 1 . L iH itk N N . J CUMPAN'i j f ' - - Mtu .A\ 3tSi'Ar?,:H :v5.os ubL: l **-- ' N <o r a : i 1 K6 1 ? , - - vs , i " A n i > t b m u 1 -a r- * - m * * B C R T M A N O f R k . N N i O S 4 O C**b m , i , < c WUWC **< * f H T .'n . - * u January 11, 1957 Mr. 0. ?. Stroop American Petrol Institute 50 Vest 50tfa Street Hew Tork 17 lev Tork Dear Mr. Stroopi I would greatly appreciate it if you would hare the attached duplicated and divtributed to the Madiera of the SubooMcittee on Carcinogenicity and to Dr. A. W. Horton of the Kettering Laboratories. It is vy understanding that the British are saasvhat put out that thay have not received anything frost us in the past several years. I suggest that the subeoswcLttee give serious thought as to what they are going to send the British so that ve can discuss it at the next nesting of our subcoaadttee. In addition, Dr. Mevquist has suggested that perhaps IT. Horton ought to auaaarlse this, and all past reports received fron the British. This occurs to m to be a good idea. In the event that Dr. Horton does not have sons of the previous infcrwation received from Ifcgland, if he would let m know I would be happy to see that he is brought up to data on anything that he nay be lacking. Vaxy truly yours, &. E. ECKAHDT, M. D. RZStcjh Attach. - Six reports ef the CoMittee on the Carcinogenic Action of Mineral Oils, Medical Research Council, London, attached to ltr to REE fro* Or. Meuquist, 1/2/57. Copy Prow D. T. Stroop for Infornatloe Of And Consideration ly Meabers Of Tbe Subcoowittee On Carcinogenicity And Dr. A. V. Horton l/lk/57 API 06277 MEDICAL RESEARCH CO U N CIL Vi REE* oiv:" Wc BEB SVH HAG fWC ARJ jav_ "fhf JHF LCM MK b JAN 3 "'Unclassified'1 f,?or Specified Circulation (Members of Connittee) "* MRC. 56/96? CAMD. Ag.2I CCMflTTEE CK THE AaSIHOggTIC ACTION OF MBgRAL OILS AGENDA for the Twenty first meeting to be held at 38 Old Queen Street, Westminster, S.W.l, an Tuesday, 18th December, 1956 at 2.30 p.nu 1. Minutes of the previous meeting (MRC.56/727, CAM0.Min.20 - already circulated) 2 . Progress Reports (a) No.XVII, November 1956 (Birmingham), by Dr. D.L. Woodhouse, (MRC.56/946, CAVO.56/9 - Enclosure A). (b) The 1955-56 Experiments with Mioe at Leeds, by Dr. J.O. Irwin, (MKJ.56/965, CAMS.56/12 - Enclosure B). (,0) Hepart by Dr. V. Cerruthers, Dr. J.W. Cook and Mr. A.G. Douglas. (MBC.56/958, CAIC.56/LI - Enclosure C). 5. Preparation of Kuwait fractions for 1957 te 1958 teets. As piorate treatment on a large scale has proved impracticable Professor Morton will suggest preparation of fractions by chromatography on alumina from KX^. A Note by Professor Morton is enclosed (MBC.56/956* GAMO.56A 0 Enclosure D). 4, Proposal for including a single specimen of cutting oil, reported to be non-csrcinogmic in the Birndnahsm teets. Manchester Oil Refineries have prepared an oil whioh, according to the Teort Formula is nan-oaroinogenicy for Messrs. Ferranti, a big user of cutting oils. This oil satisfies all the requirements from the technical point of view, and it is now suggested that it might be tested in the laboratory to see if it is in fact relatively non-oaroinogenic as far as shimals are oanoerned. If it were so, then it oould be, and perhaps should be, recommended for wider use as a cutting oil. .. Any other business. 6. Date of next meeting. API 06278 l'icuicnb r\tJcrw\v.n i-U U N CTl 'UCiUilf*1" Tor 3r*tficd iivolation [Moeibere of Comltteo) MHC.50/9V aUIO.56/9 ff.-.TTTEE OK T ig GARCINOGZNIC ACTIOis JF MJBRAL O lla P ro g re ss Report Ne. XVII . November. 956 (B littlnghmU by D .L . Woodhouae Thu fractions listed in Table 1 ware oaonanoed on 28th February and nave bean applied for 37 weeks at the ties of the report, hen the tumours indicated were observed, Fuller details ill be sutaltted at the end of the 32 week period, the present report being intended as a preliminary guide for future work. Table I Fraction Rabbit Tests Azi v b! K4S6-8 Ari W Cy Rl36-f Ari A 0) Ari Y K) Ari Z (residue) Kd36-B irli X a) K4S6.fi Arii Y H) X48M irli Z (resiluu) i) K4S6-8 Arili X J) *6-6 Arili T k ) K4S6-8 Arili Z (residue) 6) Xa36-8 Ari (originai pet. ether aluate) JO Arti (oripi.nil iene eluate) N) K^S6-8 drill (original ethanol aluate) 0) XX** (B.range 355-370 0) P) KX5-4 (B.range 370-380 C) Q) X*7-S (B.rango 380-390 C) a) OtResldue (Boiling above (53 al.) (53 al.)' (53 mi.) (53 e..) (53 a.) (15 *1.) (15 ni.) (15 mi.) (11 mi.) (11 ni.) (11 mi.) (132 ni.) (23 mi.) (17 mi.) (300 mi.) (300 mi.) (300 mi.) (300 mi.) rumours 1 0 0 l - 0 0 0 0 0 0 0 0 3 5 3 8 8) K4S8 (original Stedaan out (300 mi.) ; as standard) f) D(2) Standard as agreed U) D(i) Standard as arreed r See CAMO. 5/7 page 1, API 06279 1 MEDICAL RESEARCH CO U N CIL "Unclassified" Fer Specified Circulation (Members of Cannittee) HE. 56/96* CAJC.5V12 OOMMrngg ON THE CABdNOGBNIC ACTICK OF MINERAL OILS The 1955-56 Experiment wlth Mlco et Leeds by J. 0. Irwin The reeults far th Standards are given in Tablc 1, and for the Fraotion in Table 2. The Standard The response to were in good agreement with thoso obtained in previous years. In Table 1 these responses are coopered with the results of the three experiments carried out at Birmingham in 1952-3 1953-^ and 1954-5 and that carried out at Leeds in 1954-5 Tho response to I>2 however sees to have bean anomalous. The total number of tumours was 32 against an average of 38 In the Birmingham experience, but tumours occurred a great deal later, as ahown by the expectation of tunourloaa life and date when 1QJf of survivors had tumoura. The Fraetiona The Fractions tested were the eight Lagulnlllaa I^SnA - I^SgA and tho residue I^Sp , m Table 2 these are compared with the corresponding Kuweit fractions tested st Birmingham in 1953-4 flth one exception to L fractions ell gave a higher response than the corresponding K fractions. The difference was statistically significant for I4S5&, X4.S6&, I^Sgi, also these four fractions gave a higher response than the other L fractions. The residue I^3fi geve a positive response while K^Sp did not. In view of tho anomalous response to the standard these results should be interpreted with some caution. However, at Leeds in 1955-8 gave a lower response than Dg at Birmingham in 1953-4 and I>2 at Leeds gave a nuch lower response than D2 et Birmingham in the same year. This suggests that the Lagdnlllaa really were more potent than the corresponding Kuwait fractions, for if they ware coopered relative to the standards tested at the same time theix relative difference would be enhanced. API 06280  Table 1. Results from Standards In Mice Experiments (Leeds 1955-6) Fractions Expectation of Tumourless Life (Limited to 52 weeks) Date when 10 of Survivors had Tumouro Total nisnber of Tumoure Leeds Results (1955-6) D2 i 4 32.5 1.0 23.3 1 0.9 Leeds Results (1954-5) D2 16.1 - 1.8 D* 18.8 0.9 Birmingham Results D2 1952-3 13.9 - 0.4 3-4 12,9 - 0.6 4*5 14.4 - 2.0 I Mean 13.7 - 1.2 26.1 - 0.4 32 17.3 - 0.6 42 10.1 - 0.5 a 12.2 ~ 0.2 44 11.4 - 0.8 38 8.7 - 0.4 40 6.6 0.2 36 8.9 0.5 38 1952-3 3-4 4-5 24.8 * 1.6 18.1 0.8 17.9 - 0.8 17.1 0.6 25 10.3 - 0.6 45 11.7 * 0.3 43 Moan 2D.3 1.1 13.0 0.5 38 i API 06281 Table Results fror. Fractions in 4'icu Experiments Leeds (195^6) La^ulnlllae and Birminghsa (1953-4) Kuwait, Fractions w K4S1A Expectation of Tumourloss Life (Limited to 52 weeks) 46.0 - 2.0 50.1 - 0.6 Date when 1055 of Survivors Had Tuaours 29.4 - 2.9 not roaohod Total numberof thsoours 4 2 U S a* K4S2A 14334 W 14S4A KliSi(A 49.5 i 1.2 52 52 51.2 1 0.6 48.2 I 2.1 49.6 i 1.3 32.7 3.6 4 not reached 0 not reached 0 not reached 3 not roached 3 not reached 4 W I4S6& **** 14874 ^74 U S 8A K^SgA 42.2 i 3.5 51.2 - 0.6 43.2 1 3.0 50.7 i 1.0 39.7 i 4.1 50.4 - 1.0 36.8 1 4.0 47.3 1 1.6 27.7 1 0.6 4 not reached 2 19.7 i 3.5 7 46.3 ~ 4.0 2 17.6 1 0.6 6 43.9 1 0.6 3 17.7 i 0.4 8 28.6 1 2.3 8 USB USR 46.5 * 1.7 52 24.3 i 2.3 3 net reached 0 API 06282 m ed ica l "Unclassified* ?or 3pneiflod Circulation (Mambsro of Coaoittoo) research COUNCIL JOt.5V558 CUO.56^1 lYMfTTPKH at THE CUCIMOGWIC 1CTICX CP QTL3 a sport ty Or, f. Carruthar*, Or, J.V. Cock __________ nd Mr. d.C. Pouglas._________ Vs are continuing with otar Investigation of fractions produosd from tho K trait Oil. The distillate# obtained ty fractional distillation of the petrols* - sthor sluatso of piorats farming fractions bars yielded a tuaber of oxystalliae ubstaaoos ty crystallisation of anlanular oanrlotas aad ohrcnatography. Dlffledty has arisen la purifying thsso substonoes, bsaauas tf tbs Mall Mounts available, hut tho ultra-violet absorption spectra of tho orada aatsrlals M ots that they belong to tho olaso of phonanthraneo <r of dibonsothlcphmoo. Two ' oonpotBds havs boon eibtaiBod honogoaooua; ono Is a txi- or totra-*ethyldlbnso- thlophono, aad tho othor Is a totxa>ethylphanantfcreno, Ono of tho nothanol aluatoo (Kj.&ihlplT) obtained f r a tho Kiralt frootI b.p. 382J-3Q50 as outlined In tho lost Hoport, has yloldod a crystalline oopotnd, o.p. Tho ultra-rlolot absolution spootrua aad olmo n t uy analysis of this substance indionto that It is a panto- or hcxnHoothylonrtnsols, or tho ^dvalit. Tho OMpotnd H-)g3 Isolatod bafaro f r a fraction K^Sgfcdp (soo CIM0,5V%) hns nos boon Idontlflod ns 3-<rthyl-6i8-dincthyl-oaphtho (1i2-b) thlophono (ZZ) (Rlng-lndox nasanolnturo). ds outllnod In previous Haparts, ths bnsio 6i7-banscrthlo-naphthon ring structuro of ths oaspouid sns ohosn ty Its ultra-violJt absorption spsotrun, and dooulphiriantlon with Eanoy nlakal affordsd a naphthalene hydrocarbon OtgB2o This has nos boon Idontlflod ty syntboois as 1 s3-diaethyl-6^ggbutylaaphthaleno (ZZZ). Two passiblo struoturos (Z and ZZ) thus ronalnod for ths paraat sulphur oor^otsid. i doolslat m s mado in favour of ZZ on tho basis of ths Craethyl analysis whloh shosod tho prosonoo of only 3 Csothyl groups, ns expected for (11). Ccopotnd Z would have shown 4 suoh groups. API 06283 r TTEU l l A L k t t e a k x t xrcTxmrcrr "Unclosalfiod" Per S-oec^ed Clrculatlo!, (Masbers of Caaaittae) xx.^b/^y CUW0.56A( m a i r m r at THE URCINOGEWIC ZCTION Of HIM5RAI Oi^g Ttc .'ouowin^ programne of tests for fir. Woodhouse ess discussed st j.ndngham on 14 Novwnber by Professor Squire, Dr. Woodbouss, Or. Kin? snd Professor Morton (Dr. Csrruthers see unable to attend). The reason for the modification in the original aohaae, hioh was to prepare sanplos by the methods of separation developed by Dr. Oarruthers, is our inability to handle large quantities of pierlo said. Various industrial oonoems have beat approached tat are not prepared to undertake this work. Ve propoee therefore to undertake the separation by liquid phase chroma tography using aluslna, following the publication by Mair et el (4.C. 3. Pet.Dir. 3ept. 195^) which ahn the saste separation into polynuclear, di-ruoloor and aeno-ouoloar itios is possible, soale oannot be undertaken in our prsseat laboratory (for safety reasons; and ee therefore suggest s preliminary separation of the K X j ^ fractions (baaed on -hu Interin report of Sr. Voodhouse) to provide sasplee for the 1957-58 series at PiminghiBi and sons material for praliadnsry work by Dr. Carruthers. She proposal Involves firstly the eoetone-water extraction of S o ^ , to protaoc a aore highly aronatio axtmot and a raffinate ( K X ^ P). Tns extract KXn>6 A will than be ohrenatographed an alumina and the separation fdlloeed by refractiva index meeeum asnta on the elutrates. By this means we oaqwot to obtain tone ladioation the preparation of the Petroleum Ether, Bensene and Methanol elutretes of differenoas in the hydrooaibons used in each dutrate. Further separation of the Petroleun Ethar and Bensene elutrates will be oarried it if the refractive index aeaeumaents indicate that acne further separation le possible, she Methanol elutrsto w i n be studied only if blologioal results of the 1956 aeries indloste sons setivity. To ohook on possible loos of sotive ooqMnents taring ohroentogrsphy the slutrstes will be reblsnded in aliquot proportions snd the blond included in the test sapleo. In addition it is proposed to include: 1. The usual standards (D2 snd ty) 2. KX9, s saepl* prepared by distilling the EX railtasa in a manner smilsr to the preparation of X499. 5* At Professor Squire's request s cutting oil vhioh has bean offered sc being non-potont. ft*: list of s.wploe will not be oas^leted ixitll the examination of the olutrsteo has been diaouased with Dr. Csnuthare and Professor Squires, i.o. staples 1 2 - 2 1 may be prepared by ftotiur separation of r r '- C Ai and KX c Aii, or altoomstively Sr. Carruthers may wish to include soso inifiviCiial hydrooarbene in this serios. 1 - APi 6284 Sample Wo 1 2 3 4 5 6 7 S 9 10 11 Description D2 Standard D* Cutting oil KX? 5-6 KX^ A (To repeat 1956 tostl) (Acetone extract) 5-6 P l . 5-6 Ai K X ^ Aii (Raffinate) (Petroleum Ether elutrate) (Bensene elutrate) KX5.6 A1 (Uethanoi elutrate) Bond of X X ^ Ai, ii end iii Noa,12 -21 To be decided after examination of analysis of slutratee. Standard strength of all KX^_g sarplea to be equal to KZ^.5 A, Thus, the KXj_$ Ai etc, will be diluted with liquid paraffin to the sans volune as the KX^_g A from shioh they are prepared* API 06285 - ^ y Ml rm Al RESEARCH COUNCIL i icNpnonc WitirfhAii 4M4 I Itfetfiiuut M kM um n. Pa* i -Lokuijn 38 Old Quhn Sntarr, Wamaana, London,S.W j I ** BEB "nvh HWC `rw c ARJ JDt F HP JHK "J3 JCLklTi't. Ck, L. CAdtflOSadlC AbVU Ux iZndttAL OHS Meeting to be held et 2.30 p.a. on x'uaaday the 16th Deoaaber 1956 at 38 Old ueen Street, b.-.i. lie uttaahea report (tC.5</969,a.<).6/13) i ir discut.Io n under itea 2(b) ol the Agenda* ltth decomber 195b rLC.iiQRTa.. I API 06287 4 MEDICAL RESEARCH CO U N CIL "UnC-UlS6ified" Por Specified Circulation ^Members of Committee) ifflC.36/96$ CAMD.56/13 muMWiUi; GW IBB ACTION OP MINERAL OILS Statistical Analysis of 1955-6 Experiments with Babbits at Leeds by J. 0. Irwin An experiment with 11 fractions was carried out. The fractions eere L^SiA - L^SgA the residua L^S? together with the two standards D2 and The design of the experiment was the 11 x 5 louden square shown in Tabic 1. There arc 11 groups of 5 rabbits. In each group each rabbit was paintod with the same 5 fractions one on each of the sites I, II, III, IV, VII. Each of tho 11 sub-fractions was painted on each site in one and only one group. Each fraction was used in exactly five groups and every pair of fractions in Just two groups. Tho percentage of oach group of animal a which got tuaours on each site was calculated. In tiiis experiment there was an unusual number of tumourless deaths before the end of the year - 17 out of 55* Accordingly an allowance was aside for than. The number of animal years of exposure mas oalculated far each group. For example in the sixth group there was one tumourless death 11 weeks from the beginning of the experiment. The number of animal weeks of exposure was therefore H (4 x 52; * 215 and 219/52 * 4.2. This was rounded off to the nearest unit i.e. 4 and the three tumours on site I were considered to have occurred in 4 animals esposed for a full year. The percentage was therefore taken to be 75$ not 60%. The method of analysis was to transform percentages to degrees by moans of the angular transformation and then perform an analysie of variance of the results. Table 2 shows the mean value of the transformed variables and the probabilities of getting s tumour, estimated for esoh fraction and standard. The corresponding values of the K series tested at Birmingham in 1953-L or shown far oanparlson. The StTM*'** The results for the standards ore oonpared below with those of two previous years. Leeds 1955-6 Leeds 1954-5 Birmingham 1953-4 .627 (5L.18) .61*4 (52.27) .643 (52.19) H .521 (4 6 .0 2 ) .245 (31.84) .156 (26.63) The figure shewn is the estimated probability of getting a tumour. (The transformed variable is shown in brackets. The standard errors arc 4.2, 4.7, `'.O respectively for 1955-6, 1954-51 1953-L respectively.) The result for D^. Aemae unusually high. For D2 the agreement is good. ApI 06288 The Fractions L^S^A shows & rather low oarclnogenioity, so does I^SP, though the value for the latter 1b higher than for fySP; (the difference just about reaches the % level of significance). Otherwise there ie little difference between the response of the differont L fractions. The L fractions give a somewhat higher response than the corresponding E fraotions and this result agrees with that obtained for the mice. Analysis of Variance The analysis of variance is shown in Table 3 There are signi ficant differences between groups of rabbits, end the site differences are renaxkably large. The observed percentage of tumours on the various sites is shown in Table 4. The highest incidence is again an aites I and II (ears) and V H (middle of the back nearest ears), API 06289 .`able 1 Design for experiment with Rabbits at Leeds (1955-6) Rabbits 1 5 6 10 n - 15 16-20 21 - 2f 26-30 31 - 35 36-40 41-45 46-50 51 - 55 I II III IV VII 0 A a b e Ji.t 3 3 a c a f i h b e h ,) k a b c h g k i b 3 3 g g a k i d h S d e f i k b f 3 fc e f c 1 3 i 0 d h l4s1a I4& 1 3 0 * a W W w w H37A * 3 e b e b * i 1*384 k \S P * g Us 3 & = f aew b - I4S6A c " u ^lk d c X>2 e - V jA f 3 Di g - i^ap h 3 Li^SifA 1*w 3 * L^SjA k I^SgA API 06290 ) ) CM JN. CO API 06291 'raotian or Standard H S 1A 1*9 A h S 5A V ' 5A w W Ve4 L43P D2 Table 2 Experiment with Babbits at Leeds 1955-6 Two 3tnAtrda and eleven -derived fractions Mwn Values corrected far Group differences Leeds 1955-6 Transformed Probability Variable of Tumour 34.96 .299 52.03 .648 51.9ft .642 47.16 .546 50.06 .606 50,65 .613 52.88 .664 51-58 .636 Total Iftafcer of Tuuours 3# 10A 7 599? *Vzi 67* ^ / l B 56* UA9 5* n A 8 61* AB 72* 12A B 67* Fraction Standan K^SiA W \ s 3A w *485/1 Kj^SgA W 34.52 .288 5/2D 29* K48P 51.18 46.02 .627 .521 'V 70* D2 9A 9 47* D* S.E. one mean 4.21 Difference betweeni 5.9? two means ' Birminidiair. 1953-4 Transformed Probability Variable of Tumour 43.68 .474 25.67 41.88 .141 .438 51.57 .631 48.14 .563 52.77 38 35 49.35 .654 .566 .587 21.28 .077 52.19 26.63 .643 .156 Total Numbi; of Tumours (out of 2$ ) 10 4C* 5 ao* U 44* 14 56* 14 56* 16 64* 1C 40* 13 52* ? 8* \7 68* f, 24* 4.9 V 7.03 .`ab.. 3 iUperimunt vnth Rabbits at Leeds 1955-6 Analysis of variance on angular transfcnaation of proportion of tumours cum of Squares Degrees 6f Freedom Mean Squat Variance Ratio Sites 7478.43 4 1869.61 23.23 (P .001) Groups of 3119.77 10 311.98 3.88 (.OKPCOOl', Rabbits Fractions 2565.98 10 256.60 Error 2414.84 30 80.49 15579.02 54 Table 4 Experiment with Rabbit at Leeds 1955-6 Ntnber end Percentage of Tumours on the five different sites Site I n in IV VII Nixnbar of Tunoure 33/42 33/42 12/42 13/42 26/42 >? Turnem* 79* 79* 29* 31* 62* API 06292  MEDICAL RESEARCH COUNCIL "Vr.ciassific" F er Specified Circuir,tier. fierier3 cf 2crr-c.r"--_c) VKC. 56/969 OAMC.56/13 CgCUTTES CW THS TABSPrOGSWIS ACTION OF .'T3HAI CILS Statistical Analysis cf 1955-6 Experiments rith Rabbits at Leeds by J. 0. Imir. An experiment with 11 fractions was carried out. The fractions were Li SiA - L, SgA the residue L.SP together with the two standards I>2 and Di27 " * The design of the experiment was the 11 x 5 Youdcn square shown ir. Table 1. There are 11 groups of 5 rabbits. In each group each rabbit was painted with the same 5 fractions one on each of the sites I, II, III, IV, VII. Each of the 11 sub-fractions was painted on each site in one ar.d only one group. Each fraction was used in exactly five groups and every pair of fractions in just two groups. The percentage cf oach group of animals which got tumours on each site was calculated. In tliis experiment there was an unusual number of tumourless deaths before the ehd of the year - 17 out of 55. Accordingly an allowance was made for then. The number of animal years of exposure was calculated for each group. For example in the sixth group there was one tumourle3s death 11 weeks from the beginning of the espenaent. The nutber of animal weeks of exposure was therefore 11 + (A x 52) - 213 and 219/52 = 1.2. This was rounded off to the nearest unit i.e. 4 and the three tumours on site I were considered to nave occurred m 1 animals exposed for a full year. The percentage was therefore taken to be 75% not 60%. The method of analysis was to transform percentages to degrees by means of the angular transformation and then perform an analysis of variance of the results. Table 2 shows the mean value of the transformed variables and the probabilities of getting a tumour, estimated for each fraction and standard. The corresponding values of the K series tested at Birmingham in 1953-1 are shown for comparison. The Standards The results for the standards are compared below with those of two previous years. Leeds 1955-6 Leeds 1951-5 Birmingham 1953-1 D2 .627 (5L.16) . 6 1 1 (52.27) .613 (52.19) . 5 2 1 (1 6 .0 2 ) .215 (31.81) .156 (26.63) The figure shown i3 the estimated probability of getting a tumour. (The transformed variable is shown in brackets. The standard errors are 1.2, 1,7, 5.0 respectively for 1955-6, 1951-5i 1953-1 respectively.) The result for s e a s unusually Mgr.. For D 2 the agreement is good. - 1 - API 06297 The Tractions Li SiA shows a rather low carcinogenicity, so does L4SP, though the value for the latter is higher than for K4SP; (the difference just about reaches the *3?o level of significance). Otherwise there is little difference between the response of the different L fractions. The L ! fractions give a somewhat higher response than the corresponding K fraction and this result agrees with that obtained for the mice. Analysis of Variance The analysis of variance is shown in Table 3* There are signi ficant differences between groups of rabbits, and the site differences are remarkably large. The observed percentage of tumours on the various sites; is shown in Table 4, The highest incidence is again on sites I and II (ear and VII (middle of the back nearest ears), API 06298 MEDICAL RESEARCH CO UN CIL "Unclassified" Ter Specified Circulation (Members of Ccnmittee) KHC.56/956 GAMO.56/IO COgOTTEE ON THE CARCIKOOENIC ACTION OF MPSRAL OILS 3ugE33ted P r o g r a m e of Biological Tests at Birmingham ______________ 1957-38______________ ra) Note by Prof. P. Morton The following programme of tests for Dr. Woodhouse was discussed at Birmingham on XI* November b y Professor Squire, Dr. Woodhouse, Dr. King and Professor Morton (Dr. Carruthers was unable to attend). The reason for the modification in the original scheme, which was to prepare samples b y the methods of separation developed b y Dr. Carruthers, is our inability to handle large quantities of picric acid. Various industrial co n o e m s have been approached but are not prepared to undertake this work. We propose therefore to undertake the separation by liquid phase chroma tography using alunina, following the publication b y Mair et al (A.C.S. Pet.Div. I Sept. 1956) which shows the same separation into polynuclear, di-nuclear and I mono-nuclear aromatics is possible. The use of such technique on a large scale cannot be undertaken in our present laboratory (for safety reasons) and we therefore suggest a preliminary separation of the fractions (based on the interim report of Dr. Woodhouse) to provide saoples for the 1957-58 series at Birmingham and some material for preliminary work by Dr. Carruthers. The proposal involves firstly the acetone-water extraction of KXt_, to produce a more highly aromatic extract and a raffinate (KX5 _ P). The extract KX5 _ A will then be chromatographed on alumina and the separation followed by refractive index measurements on the elutratea. B y this means we expect to obtain acme indication during the preparation of the Petroleum Ether, Benzene and Methanol elutratea of differences in the hydrocarbons used in each elutrate. Further separation of the Petroleum Ether and 3 ensene elutratea will be carried out if the refractive index measurements indicate that some further separation is possible. The Methanol elutrate will be studied only if biological results of the 1956 series indicate some activity. To check cm possible loss of active cexponents during chranat0 graphy the elutratea will be reblended in I aliquot proportions and the blend included in the test sasples. In addition it is proposed to include: 1. The usual standards (D2 and D j ) . 2. KX9 , a aasple prepared by distilling the KX residues in a manner similar to the preparation of K4 S9 . 3. At Professor Squire's request a cutting oil ifcich has been offered as being non-potent. The list of samples will not be completed until the examination of the elutrates has been discussed with Dr. Carruthers and Professor Squires, i.e. samples 12 - 21 may be prepared by further separation of KXc_g Ai and KEc_g Ali, or alternatively Dr. Carruthers may wish to include sane individual hydrocarbons in this scries. API 06299 Sample ::c. 1 2 3 4 5 6 7 a 0 10 11 Description D2 Standard D " Cutting oil KX9 5-6 5-6* 5-6 p KX3 . 6 Ai KX5 - 6 A i E X ^ g Aiii (To repeat 1956 testa) (Acetone extract) (Raffinate) (Petroleum Ether elutrate) (Benzene elutrate) (Methanol elutrate) Blend of KX^_g Ai, ii and iii Ncs.12 - 21 To be decided after examination of analysis of elutrates. Standard strength of all KX^_g sasples to b e equal to KXc^g A. Thus, the Ai etc. will be diluted with liquid paraffin to the same volume as the KX^_g A from which they are prepared. 7.12.5C - 2API 06300 >ICAL RESEARCH COUN' L Telephone: Wk i t e h 4884 Telegrams: Medrisco, Paul-London 38 Old Queen Street, Westminster, London, S.W.l nuvy COUNCIL N I f '. ' r-* ~ GOt.UTTSE Ol xH CAROL IOGHIC ACTIQ ~ 0? I-- ISRAL 0115 % 'rtfC 0'__ >hP Ueeting to be held at 2*30 p.m. on Tuesday the 18th December 1956. at 38 Old Queen Street. S7.'l. The attached report (LRC. 56/ 969,CAL).56/13), is for discussion under item 2(b) of the Agmda. 13th December 1956 S.C.lIQRTa:. API 06301 MEDICAL Unclassified" ^oi Specified Circulation (Members of Cocaittoa) RESEARCH C O U N C IL MC.5/958 OLMO.56/11 CattHTTBB CN THB CllCIMOGBtIC action cf mdoebll QUA Report by D r. V . C arru th ers, D r. J.W . Code _________ eaa Mr. A .S . Douglas.________ We are oontinuing with our investigation of fractions produced f r a the Kisiait Oil. The distillates obtained by fmotional dietillation of the petrols < ether eluatee of piomte farming fractions hare yielded a nuaber of orywtalline substances by crystallisation of noleoular ocmplsocea and obroantograpay. Diffioulty hae ariaen in purifying these aifeetanoea, beaauae of the all -- oiw t s available, but the ultra-violet absorption spectra of the oruds naterlala diosa that they belong to the olass of phsnaathrenes or of dlbeneothiophaooe. Two compounds have been obtained homogeneous; one is a trl- or tetxa--nethyldibsnsothiophene, and the other is a totra-methylpheaanthrene. Ono of the nethanol eluatee (X^Sybtpiv) obtained f r a the Xueait fzaetiai b.p. 382^-395 as outlined In the last Report, has yielded a crystalline oanpotad, m.p. 179-181, Tho ultxa-Tiolet absorption spootra and olenontazy analysis of this libstance indiente that it is a p<nta- or heaa*oethyloaxtesole, or tho egrtmla*. The oempowd isolated befve from fraction Z^S^bhp (aee QUiO.54/4) has now bean identified as 3-ethyl~6>&41metfayl>onphtho (1:2~b) thiophene (ZZ) (Ring-index nemonolature) he outlinod in pzwvioua Reports, the basic 6:7-bensothio-oaphtheo ring structure of the oaspotad was shown bf its u l t r a - v i o l e t absorption speatr a n , and dosulphusisation with Raney nldcol afforded a naphthaleno hydroaarbon C16B2 0 This has a m boon identified by systheeie aa 1:3-diacth.yl-6-soobutylnaphtfaalona ( I H ) . Two poeaiblo etruoturoa (Z and ZZ) thus remained for the parent sulphur ooepomd. JL dooisian was oado In favour of ZZ on tho basis of the C^nethyl analysis which shewed tho proeenoo of only 3 C-- nothyl groups, as expected for (ZZ). Cabound Z would havo shown 4 suoh groups. 6th Docanbcr 1 996 API 06302 Table 2, Results from Fractions in Mice Experimenta Leeds (2955^6) La^iniilas and Birmingham fiqqyj,.) Kuwait. Fractions w K^A K4S2A L4S3A K4S3A LifSipk K4S4A K4S5A I%S 6A L4ST* K4S7A L4S8A. L^R Expectation of Tumourless Life (Limited to 52 weeks) 48.0 - 2.0 50.1 - 0.6 49.5 * 1.2 52 Date when 1095 of Survivors had Tumours 29.4 * 2.9 not reached 32.7 3.8 not reached 52 51.2 i 0.6 23.2 i 2.1 49.6 1 1.3 42.2 3.9 51.2 0.6 not reached not reached not reached not reached 27.7 i 0.6 not reached 1 1+ r0 43.2 i 3.0 50.7 1.0 J 0*7 - 4.1 -1.0 47.3 1 1.6 46.5 + 1.7 52 19.7 3.5 46.3 4.0 17.6 0.6 43.9 0.6 17.7 0.4 28.6 2.3 24.3 2.3 not reached Total number of Tumours 4 2 4 0 0 3 3 4 4 2 7 2 6 3 8 8 3 0 Table 1. Results from Standards in Mice Experiments ' (Leeds"1955-^1 ' Fractions Expectation of Tumourless Life (Limited to 52 weeks) Date when 1095 of Survivors had Tumours Total number of Tumours Leeds Results (1955-6) D2 32.5 - 1.0 23.3 * 0.9 26.1 t 0.4 32 17.3 i 0.6 42 Leeds Results (1954-5) d2 16.1 1.8 Da 18.8 i 0.9 z Birmingham Results D 2 1952-3 3-4 4t 5 13.9 * 0.4 12.9 i 0.6 14.4 ~ 2.0 Mean 13.7 1.2 Dj2. 1952-3 3-4 4-5 24.8 t 1.6 18.1 0.8 17.9 1 0.8 10.1 i 0.5 41 12.2 i 0.2 44 11.4 - 0.8 38 8.7 - 0.4 40 6.6 t 0.2 36 8.9 - 0.5 38 17.1 i 0.6 25 10.3 0.6 45 11.7 i 0.3 43 Mean 20.3 i 1.1 13.0 t 0.5 38 C_ API 06.3 04 MEDICAL RESEARCH CO U N C 'lf "Unclassified" For Speoifled Circulation (Members of Caanittee) MRC.56/965 CAMD. 56/12 COMMITTEE ON THE CARCINOGENIC ACTION OF MINERAL OILS The 1955-56 Experiments with Mice at Leeds by J. 0. Irwin The results for the Standards are given in Table 1, and for the Fraotions in Table 2. The Standards The responses to D were in good agreement with those obtained in previous years. In Table 1 these responses are compared with the results of the three experiments carried out at Birmingham in 1952-3 1953-4 and 1954-5 that carried out at Leeds in 1954-5. The response to D2 however seems to have been anomalous. The total number of tumours was 32 against an average of 33 in the Birmingham experience, but tumours occurred a great deal later, as shown by the expectation of tumourless life and date when 10 of survivors had tumours. The Fractions 3 The Fractions tested were the eight Laguinillas I^S^A - I^SgA ^ and the residue I43R In Table 2 these are compared with the corresponding Kuwait fractions tested at Birmingham in 1953-4. With one exception to L fractions all gave a higher response than the corresponding K fractions. The difference was statistically significant for I435A, I^SgA, L^StA, L^SgA, also these four fractions gave a higher response than the pther L fractions. The residue I^Sr gave a positive response while K^SRdi^t. ^ * 6 view of the anomalous response to the standard these results should be interpreted with seme caution. However, D at Leeds in 1955-6 gave a lower response than Dr at Birmingham in 1953-4 and D 2 at Leeds gave a much lower response than D2 at Birmingham in the same year. This suggests that the Laguinillas really were more potent than the corresponding Kuwait fractions, for if they were compared relative to the standards tested at the same time, their relative difference would be enhanced. API 06305 Fraction G) K4S6.e Arii Y K) Arii Z 0) KX2-4 P) KX5-6 Q) KX7-8 T) D(2) u) D(*) Table II Mouse Tests . Tumours 1 1 1 1 1 35 25 All other fractions have produced no tumours. Notes 1) For comparison of fractions 0, P, Q with fyS2 to 8 see Birmingham Report No. XII. K4S2 K4S3 K4S4 K2+S5 K4S6 K4S7 K4S8 = 6 tumours = 6 tumours = 7 tumours = 4 tumours = 5 tumours = 3 tumours = 2 tumours In rabbits all at 37 weeks. 2) Compare R with K^S^ = 3 tumours at 37 weeks (Birmingham Progress Report XVI). 3) Compare S = K^Sg with results in Birmingham Progress Reports XI and XII, i.e. 2 tumours at 37 weeks, 3 at 2+4 weeks and 6 at 52 weeks. 4) In 1954 - 55 (Birmingham Progress Report XVI) Standard D(2) gave 15 tumours at 37 weeks Standard D(4) m 2 " " 37 " In 1 9 5 3 - 5 4 (Report XII) Standard D(2) Si&cv j 3, D(if) gave tt 1C tumours at 37 weeks 6 " " 37 " r\ MEDICAL RESEARCH C O U N C IL "Unclaeeified" For Specified Circulation (Members of Concittee) ~ MRC.56/946 CAMO.56/9 nCMMTTTEE ON THE GABCINOCEKIC .ACTION OF KPraiMT. OTTS Progresa Report Wo. Z7II-. November. 1956 (Birmingham) by D.L. Woodhouae The fractions listed in Table 1 re ooenenoed on 28th February and have been applied for 37 weeks at the tine of the report, hen the timours indioated ere observed. Puller details ill be submitted at the end of the 52 weak period, the present report being Intended as a prelladnary guide for future work. Table I Fraction Rabbit Testa A) *436-8 Ari V B) *436-8 Ari W c) *436-8 Ari Z D) *4s 6-8 Ari I *) *4s6-8 Ari Z (residue) V) *4s6-8 Arii Z a) *436-8 Arii T h) gj*ii Z (residue) i) tu Z J) Hftti T *) Arili Z (residue) 1) *436-8 Ari (originai pet. ether eluate) M) *436-8 1x11 (originai iene eluate) *) 436-8 drill (original methanol eluate) 0) **2-4 (B.range 355-37D C) p) **5-6 (B.range 37D-380 C) Q) **7-8 (B.range 380-390 C) H) **Beeidue (Boiling above (53 mi.) (53 mi.) (53 mi.) (53 mi.) (53 mi.) (25 mi.) (15 mi.) (15 mi.) (Il mi.) (11 ni.) (11 mi.) (132 mi.) (23 mi.) (1 7 mi.) (300 mi.) (300 mi.) (300 mi.) (300 mi.) < Tonaure 1 0 0 0 1 4- 0 0 0 0 0 0 0 0 3 5 3 8 3) *4^8 (original Stedman cut (300 mi.) 2 aa standard) T) D( 2) Standard as agreed 11 U) D(i) Standard as agreed 8 See CIMO. 56/7 page 1. API 06307 MEDICAL RESEARCH C O U N C IL tf *l unclassified" P>` specified Circulation pV '-^-flanbers of Canmittee) V B MEC.56/963 CAMO. Ag.21 r COMMITTEE ON THE CARCINOGENIC ACTION OF MINERAL OILS >- AGENDA V l'_ for the Twenty first meeting to be held * at 38 Old Queen Street, Westminster, S.W.l, on Tuesday, 18th December, 1956 at 2.30 p.m. 1 . Minutes of the previous meeting (MEC.56/727, CAM0.Min.20 - already circulated) 2. Progress Reports:- (a) No.XVII, November 1956 (Birmingham), by Dr. D.L. Woodhouse, (MRC. 56/946, CAMO.56/9 - Enclosure A). (b) The 1955-56 Experiments with Mice at Leeds, by Dr. J.O. Irwin, . (MRC.56/965, GAMO.56/12 - Enclosure B). (c) Report by Dr. W. Carruthers, Dr. J.W. Cook and Mr. A.G. Douglas. (MRC.56/958, CAMD.56/11 - Enclosure C). 3. Preparation of Kuwait fractions for 1957 to 1958 tests. As picrate treatment on a large scale has proved impracticable Professor Morton will suggest preparation of fractions by chromatography on alumina from A Note by Professor Morton is enclosed (MRC.56/956, CAMO.56A O - Enclosure D ) . 4. Proposal for including a single specimen of cutting oil, reported to be non-carcinogenic in the Birmingham tests. Manchester Oil Refineries have prepared an oil which, according to the Twort Formula is non-carcinogenic^ for Messrs. Ferranti, a big user of cutting oils. This oil satisfies all the requirements from the technical point of view, and it is now suggested that it might be tested in the laboratory to see if it is in fact relatively non-carcinogenic as far as animals are concerned. If it were so, then it could be, and perhaps should be, reconmended for wider use as a cutting oil, 5. Any other business. 6. Date of next meeting. API 06308  * 1 MTTHtlMS ladoma tort C,L L I I OF MIDICIRI--CDU AVCHUI (1NCINNATI I. OHIO UNIVERSITY OF CINCINNATI DCFAMnKIT OF FMVINTIVf H U ICIH I AMD IMDUMTUAL HEALTH January 1J+, 1957 CABLA ADDUU: KCTLAD. CIRCII TILBFHONB: CANTOL MM Subcommittee on Carcinogenicity API Medical Advisory Committee Gentlemen: In connection with the proposed investigation of petroleum waxes, we have given serious consideration to the desirability of dividing the program into two phases, the first of which would involve a relatively rapid screening of pertinent waxes used to coat meat wrapping paper or milk cartons. If positive biological evidence of the presence of carcinogens is obtained in this first phase, a second developmental phase to estimate the hazard of internal cancers would be recommended. Dr. Eckardt has asked us to circulate the attached memorandum, which presents in some detail the reasons for the suggested phasing of the proposed investigation. Dr. Eckardt has also raised the question of the desirability of renewing the exchange of information with Research Committee No. 2 of the Institute of Petroleum. We have indicated our whole-hearted agreement with such a policy and have suggested that it might be appropriate to send copies of our annual reports on Project MC-1 for 1955 end 195c together with reprints of the papers on the determination of benzo(a)pyrene and carcinogenesis of the skin. Sincerely yours, AWH:mjg CC: Mr. D. V. S t r o o p Attachment 2 A~. Wesley H orton SUPPLEMZK7AR" PROPOSAL FOR THE INVESTIGATION OF POTENTIAL CANCERIGENIC PROPERTIES OF PETROLEUM WAXES Further consideration has been given to methods for the development of information with which to answer, in at least a preliminary way, questions about the carcinogenicity of waxes which may occur in human food. With this purpose in mind, a previous proposal involving four or five years of investigation may be divided into two parts. The first of these, if pursued vigorously, should provide some basis for the relief of apprehension, on the one hand, or point the way toward corrective measures, on the other, within 1 5 months, or possibly less, after the start of the biological tests. A significant question, selected for prompt inves tigation because it is susceptible to direct experimental attack without the necessity of developing any new techniques or concepts, is that of whether waxes used to coat wrapping paper for meat or various cartons for other foods do or do not contain polycyclic carcinogens. The skin of the mouse provides a sensitive instrument for detecting the presence of such compounds. Further, the rate of response, on the part of the skin of the mouse, may reveal the relative amounts of carcinogenic substances of this type in those waxes which do not prove to be free of them. API 06310 To obtain these answers as expeditiously as possible, concentrates of the fluorescent components of the waxes should be tested in an accelerating solvent (since the waxes are largely normal paraffins, the use of n-dcdecane for this 2 purpose is indicated). Appropriate parallel experiments with the solvent alone (negative controls) would be an essential part of the experimental program, as would also be tests with solutions of benzopyrene in n-dodecane. It should be noted that, in such experiments, the skin of the mouse would merely be used as a sensitive and reproducible means of determining the presence of polycyclic carcinogens. If no tumors are produced by fluorescent compon ents of the refined waxes, the safety of their continued use in containers for food will have gained a significant degree of support. If, on the other hand, fractions of certain of the waxes do prove to be carcinogenic, the precise signifi cance of such results will have to be determined by further * investigation. This should not prove to be very difficult, if positive results can be related to polycyclic impurities in the products tested. In any case, it should be under stood that the examination of appropriate materials by such means is recommended, not because of any notion that the use of refined waxes presents a potential hazard of cancer of the human skin, but rather because such evidence of the presence or absence of polycyclic carcinogens would be of immediate practical value. Information on the sources and properties of the waxes under investigation should oe collected carefully for this initial phase of the p r o g r a m . P a r t i c u l a r c h a r a c t e r i s t i c s , such as crude source and oil content, have been discussed previously. API 06311 - 3 Should it become apparent from the initial obser vations that some of the important waxes have carcinogenic potentialities, then a supplementary experimental program should probably be undertaken. Its objective would be the development of a biological technique for estimating the capacity of materials to induce internal cancers if ingested by human beings. Since this type of test has been sought by experienced investigators for many years without success, it would be presumptuous to suggest that a satisfactory procedure would be forthcoming promptly. Date: January lk. 1957 API 06312 Esso Research and Engineering (FORMERLY STANDARD OIL DEVELOPMENT COMPANY) P. O. Box 121. L i n d e n . N. J. Company MEDICAL RESEARCH DIVISION R O B E R T E E C K A R D T RH . D . M .D . D IR EC TO R N V H E N D R IC K S CH E H E A D IN D U S T R IA L H V O IE N IS T H O R A C E W G E R A R D E . RH D . M. D MC A D T O X IC O L O G IS T B E R T R A N D E B E N N ISO N . M D C H Ig r C L IN IC A L R E S E A R C H R H V S IC IA N jasMir n # 1997 Sr. B i U l y AOr L 1991 It is T * m j m ts M s t R s rnm t f s l s g t n S i n ts sm l l a U s is ft talssas X. V. B M 1 X , M. . *T I Is. T. i. h M as. x. M s it* m s . API 06314 O S tandard O il C om pany :d i c a l D e p a r t m e n t Y C m B. R E E V E . M. D. IID IC A L DIRECTOR U 9 0 N W. B O L Y A R D . M . D. kSSIRTA.VT MEDICAL DIRECTOR ORGE M. G O L D E N , M. D. U L D. H A L L E Y INDUSTRIAL H T G IE R I8 T 910 So u t h M i c h i g a n A v e n u e C h i c a g o so.Imi Noie January Tl, 1957 Mr. D. V. Stroop American Petroleuai Institute 59 Vest 59th Street New York 29, New York Dear Dave: In answer to your inquiry of January 11, I shorid like to request space Saturday, Aoril 29, 1957 1:09 to 5:90 P. K. for a meeting of the Sub committee on Industrial Hygiene. If this request should be in conflict with other meetings, aowever, then it will be alright with me if you set us up for a morning meeting on the sane day. Yours truly cc: L. E. Curtis, M. D Paul D. Halley LD O 1L c O RPO RAT I o N B u 1 1 r 11 N G L 0 ; a n G E l E 5 1 7 C A L I F O R N I A JOHN C. RUDDOCK, M.D. Medicol Director January 22, 1957 Mr. David V. Stroop Director, Department of Technical Services American Petroleum Institute 50 West 50th Street Rev York 20, New York Dear Dave: 3he Atmospheric Pollutants Subcomnittee has recently had a full day's meeting in Los Angeles, and there is a great deal for us to do prior to the meeting of the Medical Advisory Comnittee in order to make a report, which will require various modifications if ve do not get the $20,000 for setting up a project on the effects of air pollution (for which the petrol eum industry is responsible) on the human being. I would therefore like to request at least two hours sometime on Saturday, April 20, 1957> in one of the rooms that have been assigned for that purpose at the Sheraton Jefferson Hotel in St. Louis, Missouri. Sincerely, ' JCR:lbd RUDD0QK, M. D. ionmittee on ispheric Pollutants, Medical Advisory Comnittee to API API 06317 > 2 * \>> SHELL DEVELOPMENT COMPANY EMERYVILLE, CALIFORNIA January 18, 1957 TELEPHON* OLYM PIC 3-2100 ft1 if I -L. i x :. Vv M R MAIL \J Mr. D. V. Stroop American Petroleum Institute 50 West 50th Street New York 20, N. Y. In reply to your letter of January 11, I would appreciate your arranging tc have a meeting room available for use of the Subcommittee on C9-C12 Aromatics on Saturday, April 20, from 9:00 A.M. to 12:00 noon. While the subcommittee has only ten members, our policy will be to open the meeting to other interested members of the Medical Advisory Committee, and we will therefore appre ciate having space suitable for 30 persons. Very truly yours, CHH/jck C. H. Hine,(^*T.D., Ph.D. Consultant in Occupational Health & Industrial Toxicology API 06318 r M E D IC A L D IR E C T O R Mr. D. V. Stroop American Petroleum Institute 50 Vest 50th Street New York 20, New York Dear Mr. Stroop: In reply to your letter of Januaxy 11, I will definitely want a meeting of the Subcommittee on Economic Poisons of at least two hours for Saturday, April 20, 1957, preferably? starting at 9:00 A.M. ^ will notify the other subcommittee members as soon as you let me know the definite time. Very truly yours, JV0 :amd CC: Dr. L. E. Curtis rL V. Osborn, M.D. Zhairman Subcommittee on Economic Poisons API 06319 ~\ S tandard O il C om pany I M edical D epartment BRY CE B. R E E V E . M. D. MEDICAL DIRECTOR n elson w . bo ly a h d . m . d . A9SI9TAXT MEDICAL DIRECTOR GEORGE M. GOLDEN, M. D. P A U L D* H A L L E Y INDUSTRIAL H TO IEN IST 910 S o u t h M i c h j b a n A t x n u i : C h i c a g o so . Ixxawois Dr. David Stroop iMrioan Petroleu* Institute 50 Vest 50th Stroot How lork 20, H.I. Door Davos I wnld like to arrange for a eating of the Progran Coimlttee W to be held on Saturday April 20, 1957. At leaat two hours should be scheduled for either the oraing or afternoon, preferably the afternoon. . lours truly, BERj n .d * Medical Dlreetor API 06220 S t a n d a r d -Va c u u m O il C o m p a n y 1000 W e s t c h e s t e r a v e n t e W h ite P la in s. N ew Y o r k ROCKWELL 1 * 1 0 0 0 January 16, 1956 Mr. D. V. Stroop, American Petroleum Institute, 50 West 50th Street, New York 20, N.Y. Dear Mr. Stroop: Your advice was received regarding the Medical Advisory Committee meeting April 20 - 22, 1957* Unless something unusual arises between now and the time of the meeting, I do not expect to call a Sub-Committee Meeting on Policies and Practices. Very truly yours, KHF:ml K. R. Fourcher, M.D API 06321 \ N 1r.\< r 7 R < I t *1 -! ! '. ^ , ! f ! IF * '.'> It -7 if, E. y . tdans od 'cr!isl Research Department > jew Chsaical (Jonipany 'illland, Michigan Dear T*. Ida: Irmj 1 stter of November I, i?5t tc Paul Halley haa been referred to ae aa Chairman of tha API1 Medical Advisory Cored,ttee*a Subcommittee on Carii nogrniicivy, for answer. Is answering your inquiry, I would litce to diacuai rmc phut* of the prob.Lea separately. first, I wc-uln line tc discuss th* ralationahip of fluorescence to carclnogen- Lp*~^, The original concept that fluorescence ia a good aeasmre of oarcinoganid.ty c out of the work aor.e on the iaolation of Denzpyrene fro coal tar. It was, perhaps, fortuitous, tnat the chemists engaged in thia problem found that thooa fractions whicn ware carcinogenic to odea fluoresced in ultraviolet light. Dm, ->7 were acle to use fluorescence aa a guide to select fractions which they had preparec for biological testing. In briaf, the non-fluorescent fractions were non-carcinogenic, anc ameng the fluorescent fractions, one or more was found tc certain the biological activity, i.e,, carcinogenicity. In this way, thay wara ole ultimately to ielate oenspyrene fro coal tar. Note, however, that they did net aieintair. that 11 fluorescent fractions were carcinogenic, but only that non-ficoreanent fractions were non-e arc isogenic. Parodying a vell-fciwwn statmert, all carcinoganic fraction are fluorescent, but not all fluorescent fractions are carcinogenic. That this is true is well Known, einoe certain pure 'orpounos, such as chrysene, which fluoresce intensely, nonetheless, are completely levois cf carvinogenie artivityc c c d c , 7. w-.iuc like to discuss the carcinogenicity of U.S.r. mineral oil, Froa *. axp*rientel standpoint, G.S.P. mineral oils have probably oeen used acre -uVsnslTaly a s a solvent or vehicle for carcinogens in perimente] carcinoganic work -r.an Mtner aaterial with the exception of oemene anci ucetone. Ir. ctlcally all ruch cases, the mineral oil has beer, incepemently testec for its 'jcuiogerlcuiy is t oontrol . To my <cxjvlecLge, net one of these investigators a i TTar report--: carcinogenic kctlncy for the :J.3,P , mineral oil he used, I .Agy arid, -hat chesa inree-igators prefab'. y all used a C.S.P. sd*iral ell whicr trey purchaser '-t. -heir ^ocal drug step* and, hence, unaouDcedi?. l-.S.F. *lnera_ oil r m ; C_i. eegr nta tf the oetroieu* .rmurtry na-'t teec Vsv*d tn the -cure* -are . API 06322 Dr. . K. Adams, February 2;, lc57, - 2 - In addition, several U.S.P. mineral oils hav* ceen testec for their car cinogenicity a*, the Kettering Laboratory under the auspices of the Subcommittee of wnich I am Chairman. No evidence of carcinogenicity has been ootained in such tests. Indepenuent_y, several individual petroleum companies have hac their U.S.P. minerax oil tested for carcinogenicity, with results confirming those obtained at the Kettering Laboratory. Medicinally, U.S.P. mineral oil has been consumed in enormous quantities. In incivldual cases this may be as higr. as yj cc. tnree times a day, consumed sally for 20-30 years. To my Knowledge, no clinical reports have arisen out of such usage which would suggest that U.S.P. mineral oil is carcinogenic to rrumans. Cosmetically, U.S.P. mineral oils have Been daubed and patted daily on the !dn o' hundreds of thousands of humans over extended periods of time, again with rc clinical suggestion of a carcinogenic effect. .S.P. mineral oils have Deer injected subcutaneously into hundreds, if not rcrusands, of humans when used as an adjuvant for certain vaccines, again with out trie slightest clinical evidence of a carcinogenic effect. I may add, that such medicinal and cosmetic uses of U.S.P. mineral oil undoubtedly .nave encompassed U.S.P. mineral oils originating from all petroleum industry sources of this material, and not just one manufacturer. .rally, a recent regulation in England has made it necessary to lubricate spindles with white oils in order to eliminate the occupational cancer hazard in *.ne weaving industry. This is recognition by the British authorities that even ndustrial white oils, which are similar to, but not as highly refined as, U.S.P. mineral oils, are devoid of carcinogenic activity. '.S.P. mineral oils are highly acic-treated. The quantity and strength of acid j?ec are far in excess of that used in treating, let us say, lubricating oils. T.-is ac'd treatment removes unsaturates, which are responsible for tne distinctive :Cior ana taste of less refined" petroleum oils. The unique characteristic of ..S.P. mineral oils is their lack of color (hence, the name white oils^ and taste, characteristics which must re maintained even after long periods of storage. Thus, it appears that the weight of experimentt_ Biological, clinical epidemiological, ar.d chemical eviaence all substantiate the non-carcinogenicity of U.S.P. mineral oils. These data must, of course, be weighed against the opinion of the cancer API 06323 O ' r . E. y.. Adam, Feoruary 1c , 17.-", - 3 expert whom you cite, whose opinion is ooviously based on rather archaic thinking acoir. uhe relationship of fluorescence zo carcinogenicity. *'ery truly yours, ROBERT E. ECKARDT, M. D., Chairman Subcommittee on Carcinogenicity Medical Advisory Committee . W. Anams . K. Hine, M. D. E. K. Linder, M. 1. R. C. Mithoff, M. I:. M. N. Nevquist, M. D. A. C. Pabst API 06324 r- ^ A Esso Research and Engineering (FORMERLY STANDARD OIL DEVELOPMENT COMPANY) P O. B o x 121, L i s t e n . N J. Company medical r e s e a r c h division p O * " T C. E C K A R O T . F H ., M -D . D IR E C T O R N v. H E N D R I C K S . C H . E . H E A D IN D U ST R IA I. H V O IEN IST HORACE W . Q E R A R D E . F H .D ..M .O . H E A D T O X IC O L .O O IST flR T R A N D C. B E N N IS O N . M .O . CH IEF C L IN IC A L . R E S E A R C H R H V S IC IA N February 19, 1957 Messrs; 1 V, Adams C, Hj Hire* E, K0 Linder R. C. Mithoff N. Nevquist Ao C, Psbst Gentlaer. i I m attaching a. tentative draft of the minutes of car last nesting,, Z TBaolii ipprcriate say assents, suggestions, or additions which r i ' Two aefet ho these mlamtae before 1 prepare than is final ffcr0 It sight appear advisable to circulate these minutes te the MAC after they ara prepared, la final fon&o Sincerely yours, ?w6 ECKAHDT, M. D. IZEteJb Attach. - Minutes of the Meeting of the Subcommittee on Carcinogenicity, Reid at the Biltaore Hotel, Los Angeles on January 31 - February 1, 1957 R* Eeleardt, M. D0 (February 18, 1957) oat lr,, Lc 1., Cfcirtie / Mr. Do V, SDwapv * - In Duplicate b" API 06325 :mJUTES OF TEE KEETIHO OF THE SDBCGKMITTEE ON GARCIHCGEIilCITr Held at he Biltaicre Hotel, Los Angeles January 31 February ls 1957 The nee-ting vas cslice' to order at lOtOO a,,a,, January 31 la Dr. R. E. Eckardt'e suite at the Bilticore Hotel In attendance vaz-e the following s Ro Ec Eckardt, M. B. - Chairman N W, Bolyard (representing E, W. Adam) E* K. Daniels (representing A, C. Rabat) C,, H. Eiae, K. D. E0 K,, Linder, M. D K., Nu Hewquist, K. D. Ho Co Kithoff, Mo Do 7 'first order cf business of the Subcconittee was to review the proposals of the isris laboratories for the study of carcinogenicity of petroleun waxes Copies of the proposals obtained free* each laboratory were given to each of the mashers of the Subcomsittae ar.d the Subcomaittee then adjourned for an hour to pexmit each individual an opportunity to review each proposal `Than the Subcommittee reconvened, Dr Hise had prepared a sumsaiy of the items which acch laboratory planned to study for comparative purposes. It was then decided by the Subcoanittee, after reviewing each of the proposals, that any one of the laboratories :culd probably conduct a satisfactory study, cut same proposals showed more Imagination than others Each Subcommittee member was asked to express bis opinion as to his first choice of a laboratory in which the studies should be conducted,, On this basis, four of the lr.boratories were selected and three were eliminated. Hast, each Subcommittee member was asked to rank the four laboratories so selected and one of the four laboratories was eliminated in this fashion Since there wasn't a unanimous opinion concerning which of these should be recommended, it was decided uo reeccnsnd all three, but to rank them in accordance with the preferences of the fubco.xi.ttce, based upon a proportional representation vote to be undertaken the following dry., after each Subccmarlttoe member had an opportunity to re-rrriev the proposals cf the three laboratories concerned Results indicated preferences in the following order: 1. Hr. Philipps Sfcubik's laboratory 2 '.'he Kgzletcn Laboratories 3 b*. Lorten Nelscn**: laboratory API 06326 A, Status report by Dr, Horton 3* rii.sl report by It Pheir C0 Budget proposals for the tnterral of July 1, 1958 to June 30, 1959 from Dr., Sehoe This indorsation has been trananittod to the Kettering Laboratory representatives and the above meeting date and desire for the reports oppressed in the letter from the ChaIncan, The final order of business discussed wea a mestiig of ths Subcommittee at the tlx of the Industrial Health Conference in St, Louie, It was irrneri that an pen resting at which all MAC members ueuld be velesmed, sill be eeheduled far Saterdsy, April 20 at 3too pa, at the ShantcDoJeffarson Hotel is St, Louis, The plea rill be to have the draft report of the Subcommittee to the 1IAC prepared and distributed to all members of the MAC end to have the diecussion at the meeting on .pril 20, sinply be a shipping up into final fen of tha report for the MAC, There van also seme discussion by tha Cbbcenaitteo of the possible eareiaegenic Suf cis of sixvblowijg asphalt and ell siste ofidah adgfat occur vithin tha refinery. In ihls ecancetion, Dr. Sekardt reported to tha Subcommittee, the work which Esso Eesaaxeh and Engineering Camany had sponsored at HTU, This work had shown that the condensate of ths fume obtained with air->blewing of asphalt was highly carcinogenic to the akin of the mouse nnd that the material sertpped off a fan blade which was used to ventilate a slurry oil pop, was also caxciBogamle to the skin of the mouse, Dr, Eckardt warmed that only cbo ftame of an asphalt had base tested and it wuc not, therefore, possible to m y that all asphalt blowing fumes are carcinogenic The consensus of the SUbocaadttoa oo these problems saemed to be that it probably represented an individual eompany problem, but that if there as enough general Interest in it, perhaps ths Subcommittee could censlder experimental work on it at some future date. The Subcommittee was of the opinion that the work at the lettering Laboratory had essentially fulfilled its purposes sad that ths work probably would be terminated as of July 1, 1959 o The Subooamittoe seating camtlamed late the morolac of February 1 sad obeut one-half an hour before the Scbottialttoo adjourned, Dr, Kehoe was asked to jsir the Subcommittee meeting. At this time, be was informed abcait the meeting on pril 2 and the desire of the Subcommittee for the reports by March 25o In additien, he was irfarmed that it vsa the feeling of the Subcosmlttee that the carcinogenic work at l ettering laboratory would be tesmlnated as of July 1, 1959. Hope wsa expressed to Dr, Eohoe that an adequate final report of the work at Kettering Laboratory would be nx.de available to the Subcommittee at the time of the termination of :he work on July 1, 1?5?~ Minutes Prepared By Ru E, Eckarct. K0 Dc = Chairman February 16, 3957 API 06328 - 2- The next order of business discussed as henr to izqploent a survey of ax uses for the guidance of the biological work It as the consensus of the Subeoaeittee that our recoaoendations on this vere cleared at the April meeting of the MAC and that e had no further responsibility in this direction* The next order of business concerned the draft letter by the hieh be proposed to be sent to Dr* E. M. Adams of the Bov Chemical Coqpany. Apparently the Subcaamittee members did not understand that this letter as to ha cleared through Mr. Stroop8e office and therefore uuld receiTe clearance by Mr* Streep through Mr. Porter before it as sent out. When this situation as explained, the Subcommittee as is unanimous agreement that the letter should be sent to Dr. Adams under the signature of the Piae-- * of the Subcommittee, acting as Chairman of the Subeoaeittee, asscaling that there ere no objections to his course of action by Hr* Stroop. Upon returning to New Terk, the Chairman called Mr. Stroop and as informed that there vere no objections to sending cut this letter end, hence, arrangements have bean aade to obtain API stationery and forward this letter to Dr. Adams on API Stationery as a statement of the Suboomslttee, signed by the Subcommittee Chairman* ' The next order of business was a discussion of that rf be sent to the Institute f Petroleum in Britain by our Subcommittee* There as a general consensus that ve should send Dr, Horton9s 1955 and 1956 reports along vith the minutes of the Subccamittee meetings during the years 1955 and 1956* It vas felt desirable that this information seat to Great Britain should be sent from Mr. Stroop"s office and that future correspondence from the Institute of Petroleum In Britain be forwarded to our Subcoanlttee through Mr. Strocpes office* Is other words, it Should be addressed to Mr. Stroop to the attemtieo of the Chairman of the Subcommittee on Carcinogenicity. Is lids way, eras though changes occur in the cf the Skbooendttee, it will be possible to see that the information gets to the Subcommittee Chairman. At the eaxse time, the question of tm-- arising the British work vas brought up and it as damaed undesirable to have Dr. Horton prepare such a auamaxy. It vas proposed that a member of the Subcommittee prepare such a mamaxy and it as further suggested that Dr. Hine be so ^pointed. Therefore, I am this appointment as Chairman now. The next order of business discussed vas the next meeting of the SubcoaakLttee. It as agreed that this should be held on April 2 in Chicago. An sttwapt be made by the Chairman to reserve a suite at the Blackstone Hotel so that the meeting can be bald in his suite on April 2. It vaa suggested that it would be extremely helpful to the Subcommittee members if they could obtain by March 25 from the Kettering Laboratory the following: API 06327 X ./ i American Petroleum Institute N ew Y o r k 20. N . Y . - . SION OF M ARKETING A v Qj MOSHOSKY OiMKCTOM March i, 1 957 O FFICERS JA K E L H A M O N c h a ir m a n OF BOARO 5 ENER4 L c o m m it t e e m T C O l l Ey . chairman t a n l Ey 0 B R EITW EISER . * G KING JR BCCM TARV V>ct ch a ir m a n FRANK M RORTER *Ra<DfNT A A BUZZ) vtCC PRKS-OCNT 0 T C O l l E y v i e s p r c s <o c n t 0 L C O N N E L L Y VICE PRESIDES'* H W FERGUSON vice PRESiOEs* t A AL0RIOGE P E ALL.AN ROBERT O ANOCRSON 1SPENCER C BAGGB C BAKER BAXTER F. BALL $ C BARTLETT v A BELLMAN OWiGWTF BENTON MARC f b r a e c k e l c w BURNS f j 0HN CUMMINS royal E DECKER 1 p a u l OEER B E SEVERE jamES A OOCTOR 5 m GEORGE DONOVAN - Ell io t t j B Fisher * e Fitzg erald , 0 nORMAN FOLEY , FRASER GOLDMAN GOULO JR ^ GU2ZO Mr. D. T. Staples T idew ater Oil Company 79 N ew M ontgom ery S tr e e t San F ran cisco 20, California r O PRIOR VICE PRCSlOENT B JENNINGS TREASURER LACEY WALKER, secretary Dear Mr. Staples: With regard to your le tte r of F ebruary 12th, I have no objection to the proposed continuation of a study of carcinogenicity and concur that the sum of $50, 000 be m ade availab le to co v er the cost of carcinogenic testing of w axes by an independent laboratory. ' n A MARGIN C Z HARDWICK j OmN haRRER CASH B HAWLEY I b eliev e that this action should not be linked in the m an ner shown in the draft letter to Dr. Burney, Surgeon-G eneral of C O HILL WALTER L HOLMGREN J HULL ROBERT M JENNEY ( A TOM JONES J G JOROAN L R KAMPERMAN MARRY j KENNEOV R l KENT C K k ETCham fJESS 0 KNOWLES KOONTZ FRANK C LOVE E H l YON I w MAJEWSKI FRANK R MAPk l EY c h MEEOER M'.ES M MILLS ' B MURPHY ESl E R NEAL JOSEPH L NOLAN RE C A PENTiCO H * RAPP S . RAV 8 ROSENWA: - SAUNOERS "ENRv ^ SCHWAR1 the U. S. Public Health S erv ice. From the d iscu ssio n s in the Sub com m ittee on C arcinogenicity, it is apparent that there was m isq u o tation and m isin terp reta tio n of the statem en ts m ade by D r. H ueper. T hese m isin terp reta tio n s did lead to unfortunate p u blicity. H ow ever, I b eliev e it would be a m istak e to tie this in any way as a b a sis for the further can cer resea rch proposal by the M edical and Health Com m ittee of the API. T herefore, it is m y recom m endation that the letter to Dr. Burney be om itted. C ord ia lly , SENECAw JR STan^on k S mith : AvuiE STARTER . C STEWA JESSE STiCk El -S-E w SWEET *c' . >OMPSON v *08v JR ***** h UTLEY . JASOER JAGT G VESPEI / * A WA*T 5 C***r w E.wS .O ' h SAs - -AhC TW[EST s 6 w wnES be: Mr. Frank M. P or te r D. T. Colley A P J 06329 __L-'r r^iox O il o p (Im j p o k s i a UNION OH. B U ILD IN G L O S A Wist JURS n , C - A U F O K m R IC H A R D C ALL. M. D. M E D IC A L D IR E C TO R March k, 1?57 Mr. David Stroop American Petroleum Institute 50 W 50th Street New York 20, N. Y. , -L. * C Dear Mr. Stroop: I am in receipt of your kind letter of February 5, 1957 In reference to closing out of your inventory. Would you please send me a copy of : 1. "Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," -f5&} 2. Report of Progress in the Appraisal of the Potential < Carcinogenic Properties of American Petroleum Products," W T'hn.n'iHng you for your consideration, I remain, Sincerely yours, Richard Call, M.D. 6* * n ^ ,V 1 T API 06330 INVENTORY OF MAC CIRCULARS, REPORTS, ETC. OH HAND FEBRUARY, 1957 ). of opies 100 "Occupational Cancer - A Challenge to the Physician," by the Office of Public Health Education, H. Y. State Department of Health. 58 "Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," Report of the Progress in the Epidemiological Studies, The Kettering Laboratory, Dept, of Preventive Medicine A Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 70 "Tabular Summary of Current and Completed Biological Experiments," API Res. Project MC-1, September 1, 1953, The Kettering Laboratory, Dept, of Preventive Medicine A Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 38 "Skin Cancer of the Hand and Forearm," by C. H. D. Cruickshank and A. Goure- viteb. A "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," The Kettering Laboratory, Dept, of Preven tive Medicine & Industrial Health, College of Medicine, University of Cin cinnati, Cincinnati, Ohio. 20 "Thermal Burns," Revised draft by Dr. A. 0. Seeler. ** "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," - The Kettering Laboratory, Dept, of Pre ventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. l6 "The Cutting Oil Dermatoses - A Review," by Bertrand C. Kriete, A. B., Harvard School of Public Health, March 15, 1950. 100 "Estimated Budget of the Kettering Laboratory for the Investigation of Potential Health Problems of the Petroleum Industry Associated with the Presence of Carcinogenic Compounds in Certain Materials and Products API Research Project MC-1, July 1, 195^ - June 30, 1955." 25 "American Petroleum Institute Medical Advisory Committee Report for Period 19^5 - 1952." 75 "Tabular Summary of Current & Completed Biological Experiments, September 1, 1953," The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. ^5 "BAL," by Raymond V. Randall, M. D., and Albert 0. Seeler, M. D. API 06334 11 "Interim Report API Research Project MC-1, October 1, 1955," by The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. ,0 "Cutting Oil Dermatoses," by Harry Shapiro, M. D., N. Y. State Dept, of Labor Monthly Review, Division of Industrial Hygiene & Safety Standards.3 3 "Supervisory Development Services Available from Public and Private Agencies and Institutions," compiled by the API Comm. cr. Supervisory Development. 2 No. of Copies QO "Determination of Benzo(a) - pyrene in Complex Mixtures, Use of Catalytic Iodination on Activated Alumina," By Russel Tye, Mary Jane Graf, and A. Wesley Horton, Kettering Laboratory, University of Cincinnati, Cincinnati, Ohio, Reprinted from ANALYTICAL CHEMISTRY, Vol. 27, Page 2 k 8 , February, 1955 183 "Carcinogenesis of the Skin. A Re-examination of Methods for the Quantitative Measurement of the Potencies of Complex Materials," by A. Wesley Horton and Dorothy T. Denman, reprinted from CANCER RESEARCH, Vol. 15, No. 11, pp. 701-09, December, 1955. 28 "Phosphate Ester Insecticides," by D. 0. Hamblin, M.D., H. H. Golz, M. D., F.A.C.P., and C. B. Shaffer, Ph.D. 35 Revised manuscript of paper entitled "Carcinogenesis of the Skin," by Dr. A. Wesley Horton and Dorothy Templeton Denman. 12 Committee on the Carcinogenic Action of Mineral Oils, Meeting held May 2, 1955, at 33, Old Queen Street, Westminster, London, S.W.l, three Progress Reports. API 06335 I ) I THE TEXAS COMPANY 135 EAST 42* STREET N E W Y O R K 17, N Y API 06336 ) ) vi/' ^ -- ' * r U i'iii! i-* .Viri * .*/k . , . >1 Mr, D. V. Stroop American Petroleum Institute 50 West 50 Street Mew York, N. Y. ; * *;) I!1 ` v,y / M f ' , i f VL ,*/ 1 ) <41 INVENTORY OF MAC CIRCULARS. REPORTS. ETC. ON HAND FEBRUARY. 1957 Nn. of Copies 100 "Occupational Cancer - A Challenge to the Physician," by the Office of Public Health Education, N. Y. State Department of Health. 58 "Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," Report of the Progress in the Epidemiological Studies, The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 70 "Tabular Summary of Current and Completed Biological Experiments," API Res. Project MC-1, September 1, 1953, The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 38 "Skin Cancer of the Hand and Forearm," by C. N. D. Cruickshank and A. Goure- vitch. k "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," The Kettering Laboratory, Dept, of Preven tive Medicine & Industrial Health, College of Medicine, University of Cin cinnati, Cincinnati, Ohio. 20 "Thermal Burns," Revised draft by Dr. A. 0. Seeler. 7 "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," - The Kettering Laboratory, Dept, of Pre ventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 16 "The Cutting Oil Dermatoses - A Review," by Bertrand C. Kriete, A. B., Harvard School of Public Health, March 15, 1950. 100 "Estimated Budget of the Kettering Laboratory for the Investigation of Potential Health Problems of the Petroleum Industry Associated with the Presence of Carcinogenic Compounds in Certain Materials and Products API Research Project MC-1, July 1, 1951* - June 30, 1955." 25 "American Petroleum Institute Medical Advisory Committee Report for Period 19^5 - 1952." 75 "Tabular^Summary of Current & Completed Biological Experiments, September 1, 1953," The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. ^5 "BAL," by Raymond V. Randall, M. D., and Albert 0. Seeler, M. D. API 06337 11 "Interim Report API Research Project MC-1, October 1, 1955," by The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 0 "Cutting Oil Dermatoses," by Harry Shapiro, M. D., N. Y. State Dept, of Labor Monthly Review, Division of Industrial Hygiene & Safety Standards. 3 "Supervisory Development Services Available from Public and Private Agencies and Institutions, compiled by the AFI Comn. cn Supervisory Development.  2 - No. of Copies 00 "Determination of Benzo(a) - pyrene in Complex Mixtures, Use of Catalytic Iodination on Activated Alumina," by Russel Tye, Mary Jane Graf, and A. Wesley Horton, Kettering Laboratory, University of Cincinnati, Cincinnati, Ohio, Reprinted from ANALYTICAL CHEMISTRY, Vol. 27, Page 248, February, 1955 105 "Carcinogenesis of the Skin. A Re-examination of Methods for the Quantitative Measurement of the Potencies of Complex Materials," by A. Wesley Horton and ' Dorothy T. Denman, reprinted from CANCER RESEARCH, Vol. 15, No. 11, pp. 701-09, December, 1955* ,\ 28 'J "Phosphate Ester Insecticides," by D. 0. Hamblin, M.D., B. H. Golz, M. D., F.A.C.P., and C. B. Shaffer, Fb.D. 35 Revised manuscript of paper entitled "Carcinogenesis of the Skin," by Dr. A. Wesley Horton and Dorothy Templeton Denman. 1 12 Committee on the Carcinogenic Action of Mineral Oils, Meeting held May 2, 1955t at 36, Old Queen Street, Westminster, London, S.W.l, three Progress Reports. API 06338 4 RICHFIELD OIL C O R P O R A T I O N R I C H F I E L D B U I L D I N G 555 S O U I H F L O W E R ST RE ET LOS A N G E L E S 17, C A L I F O R N I A AIR MAIL Mr. David V. Stroop Director, Department of Technical American Petroleum Institute 50 West ^Oth Street Mew York 20, Mew York Services Esso Research and engineering (FORMERLY STANDARD OIL DEVELOPMENT COMPANY) P. O. B o x 121. L i x o - s . N. J. vIED'CAL RESEARCH DIVISION R O B E " E E C K A R C T M. O M D SIRCCTOB N V H E N D R IC K S C*-* E -.C A O S :jS T f l!A w M V O U N IS " HO RACE W G ERARO E PH O M O C A O "O X IC O U O G IS T B ERTR A N D E SENNISON M D C-iCF- C .IN IC A L R E S IA H C H 0 -V S1C IA N Com pany V AT A J '/ " February 26, 1957 v y N Mr. I. V. Stroop American Petroleum Institut 50 West 50th Street New York 20, New Tork Dear Mr. Stroopx / In response to your letter ofJwbruaxy 25 I would reatly appreciate receiving(25jreprints of the two papers hr Dr. Horton. Onfcof which appeared In ANALYTICAL CHEMISTRY and the other in CANCER RESEARCH. Thank you. Sincerely yours, J l.ie J k ^ y h R. E. ECKARDT, M. D. REExcjh API 06340 f ;a. DEPARTMENT A r r c R D * V `S m o S j N T lN CTO N m o M MERY M 3 " ttS T 63 C * - 0 #E C T$ *N E REN ES ' * - - VC c n 't PHILLIPS Mr. D. V. Stroop America Petroleum Institute 50 West 50th Street Mew York 20, New York Dear Dave: Received your letter of February 25, 1957 and am returning the list of circulars, marking the ones that I would appreciate receiving. KD:tmd Enclosure API 06341 * : e'^f'T'once Tnc? Counts = -- TRQP-ARTlC J ' INVENTORY OF MAC CIRCULARS, REFORTS, ETC. ON HAND - FEBRUARY, 1957 :is. cf Copies \ \igo "Occupational Cancer - A Challenge to the Physician," by the Office of Public Health Education, N. Y. State Department of Health. 58 "Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," Report of the Progress in the Epidemiological Studies, The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 70 "Tabular Summary of Current and Completed Biological Experiments," API Res. Project MC-1, September 1, 1953, The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 38 "Skin Cancer of the Hand and Forearm," by C. N. D. Cruickshank and A. Goure- vitch. U "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," The Kettering Laboratory, Dept, of Preven tive Medicine & Industrial Health, College of Medicine, University of Cin cinnati, Cincinnati, Ohio. *20 "Thermal Burns," Revised draft by Dr. A. 0. Seeler. 7 "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," - The Kettering Laboratory, Dept, of Pre ventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. `l6 "The Cutting Oil Dermatoses - A Review," by Bertrand n . Kriete, A. B., Harvard School of Public Health, March 15, 1950. 100 "Estimated Budget of the Kettering Laboratory for the Investigation of Potential Health Problems of the Petroleum Industry Associated with the Presence of Carcinogenic Compounds in Certain Materials and Products API Research Project MC-1, July 1 , 1951* - June 30, 1955." 25 "American Petroleum Institute Medical Advisory Committee Report for Period 191*5 . 1952." 75 "Tabular Summary of Current & Completed Biological Experiments, September 1, 1953," The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. +5 "BAL," by Raymond V. Randall, M. D., and Albert 0. Seeler, M. D. 11 "Interim Report API Research Project MC-1, October 1, 1955," by The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 0 "Cutting Oil Dermatoses," by Harry Shapiro, M. D., N. Y. State Dept, of Labor Monthly Review, Division of Industrial Hygiene & Safety Standards.3 3 "Supervisory Development Services Available from Public and Private Agencies and Institutions," compiled by the API Comm. cr. Supervisory Development. API 06342 2 No. of Copies ` 80 "Determination of Benzo(a) - pyrene in Complex Mixtures, Use of Catalytic Iodination on Activated Alumina," by Russel Tye, Mary Jane Graf, and A. Wesley Horton, Kettering Laboratory, University of Cincinnati, Cincinnati, Ohio, Reprinted from ANALYTICAL CHEMISTRY, Vol. 27, Page 2U8, February, 1955- ^105 ^28 - "Carcinogenesis of the Skin. A Re-examination of Methods for the Quantitative Measurement of the Potencies of Complex Materials," by A. Wesley Horton and Dorothy T. Denman, reprinted from CANCER RESEARCH, Vol. 15, No. 11, pp. 701-09, December, 1955 "Phosphate Ester Insecticides," by D. 0. Hamblin, M.D., H. H. Golz, M. D., F.A.C.P., and C. B. Shaffer, Ph.D. \ ^ 35 j \ ^12 Revised manuscript of paper entitled "Carcinogenesis of the Skin," by Dr. A. Wesley Horton and Dorothy Templeton Denman. Committee on the Carcinogenic Action of Mineral Oils, Meeting held May 2, 1955, at 38, Old Queen Street, Westminster, London, S.W.l, three Progress Reports. API 06343 Him b le O il & R e f in in g MEDICAL DIVISION Com pany . p i iflD ,,STO* M 0 c t* : * - - 2s r -ic * s* o-u -sic* r- v ; -.-ns.* a : *rs s* BOX 2180. HOUSTON TEXAS BC * 950. BAYTOWN. TEXAS February 26, -9?S'"? 8 .V = r - s _EAN MC S-I S- 9S '5 t' r ZOOD * '- u 3 bOO s Mr. D. V. Stroop American Petroleum Institute 50 West 5A h Street New Yorn 2l , N.Y. Dear Mr. Stroop: Please send the checked items, and the number of each, on the attached _ist. Very truly yours, JW'H:sp 2nd. II API 06347 4 INVENTORY OF MAC CIRCULARS, REPORTS, ETC. ON HAND FEBRUARY, 1957 cf Topies/^ IOC /'Occupational Cancer - A Challenge to the Physician," by the Office of ' Public Health Education, N. Y. State Department of Health. 58 a ? "Appraisal of the Potential Carcinogenic Properties of American Petroleum ^ Products," Report of the Progress in the Epidemiological Studies, The * Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 70 "Tabular Summary of Current and Completed Biological Experiments," API Res. Project MC-1, September 1, 1953, The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 3 8 @ "Skin Cancer of the Hand and Forearm," by C. N. D. Cruicksbank and A. Goure`"'vitch. U "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," The Kettering Laboratory, Dept, of Preven tive Medicine & Industrial Health, College of Medicine, University of Cin cinnati, Cincinnati, Ohio. 20^/"Thermal Burns," Revised draft by Dr. A. 0. Seeler. 7 "Report of Progress in the Appraisal of the Potential Carcinogenic Properties of American Petroleum Products," - The Kettering Laboratory, Dept. of Pre ventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. l f? "Tile Cutting Oil Dermatoses - A Review," by Bertrand C. Kriete, A, B., Harvard `"'School of Public Health, March 15, 1950* 100 "Estimated Budget of the Kettering Laboratory for the Investigation of Potential Health Problems of the Petroleum Industry Associated with the Presence of Carcinogenic Compounds in Certain Materials and Products API Research Project MC-1, July 1, 195^ - June 30, 1955*" 25 "American Petroleum Institute Medical Advisory Committee Report for Period 19L5 - 1952." 75 "Tabular Summary of Current & Completed Biological Experiments, September 1, 1953," The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. '5 "BAL," by Raymond V. Randall, M. D., and Albert 0. Seeler, M. D. 11 "Interim Report API Research Project MC-1, October 1, 1955," by The Kettering Laboratory, Dept, of Preventive Medicine & Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. 0 "Cutting Oil Dermatoses," by Harry Shapiro, M. D., N. Y. State Dept, of Labor `"'Monthly Review, Division of Industrial Hygiene & Safety Standards. 3 "Supervisory Development Services Available from Public and Private Agencies and Institutions," compiled cy the A.PI Comm. or. Supervisory Development. API 06348 T 2 | No. of ! Copies 80 "Determination of Benzo(a) - pyrene in Complex Mixtures, Use of Catalytic Iodination on Activated Alumina," by Russel Tye, Mary Jane Graf, and A. Wesley Horton, Kettering Laboratory, University of Cincinnati, Cincinnati, Ohio, Reprinted from ANALYTICAL CHEMISTRY, Vol. 27, Page 2W3, February, 1955 185 "Carcinogenesis of the Skin. A Re-examination of Methods for the Quantitative Measurement of the Potencies of Complex Materials," by A. Wesley Horton and Dorothy T. Denman, reprinted from CANCER RESEARCH, Vol. 15, No. 11, pp. 701-09, December, 1955 28 "Phosphate Ester Insecticides," by D. 0. Hamblin, M.D., H. H. Golz, M. D., F.A.C.P., and C. B. Shaffer, Ph.D. 35 Revised manuscript of paper entitled "Carcinogenesis of the Skin," by Dr. A. Wesley Horton and Dorothy Templeton Denman. 12 Committee on the Carcinogenic Action of Mineral Oils, Meeting held May 2, 1955, at 33, Old Queen Street, Westminster, London, S.W.l, three Progress Reports. API 06349 Flit! MAC * i m m 17# 1337 w l i l M w f t , M B. API 06350 A LCO P R O D l'C T S E X H O R T C O M PA N Y . INC. Lt.C o l .S. J. M. A u l d 's (Eompfimenl,!. 25. VICTORIA STREET, LONDON, S.W.I. I 1 - j I ! ! j 1 .4 t API 06351 I '-- 1 /roiMnor 7 FtrguMn, nivpsit/ of l m e m 0/ toll mito a mito toilsi-- , li ^ n l n n l t j t o i a a i f ^ABvMN| tf, B Dear Professor Ferguson? ?l t o t , I B M , Ttoto in Wkwi t o m m m to t n a i l K j m to i n r t o f l i t o l a 2 k m H v m r f to m l to. totortt's m i M i i m (a ) t m n i p t M M t o r t S t o B sito A m i m m to m tornito A . / J . (to i i w ^ ) m i to API 06352 9 9 adrooood iirootly tortai, (bj u * t ottonai f V M tbt jj u lite (it^r M i M . C , or r m M i v M w l M f e c n f U JUf. tewittte) bo M I llftetlj it ir, teterdl So la m io la m loooot l o M M I 9 dirws, ho voul i h o inai of oaptkiag M I W M tt'lftf Oh (> M I M O W i p a M l So glfO tO U t MlMOfi visito tettoM M l v i t e a l i m labooodocioo utrirHti fr a &o tho i U w o t t o n a i llS o o a llj by tbo or a. i*i t m of ito oloolaa p of . i n u m Saoia MlOlf la tioa r ' S f m i ult b o o m or u t gltoa PI ffclo /a Jn/isJ S.J.M. Auld API 06353 V 91 S J M AU LD 3775 TELEPHON E ABBEV 25. V IC T O R IA STREET LO N D O N . S W I 5th April, 1957 D.V. Stroop Esq., American Petroleum Institute, 50 West 50th Street, New York. 20. N.Y. Dear Mr, Stroop, J I am greatly obliged for your letter of March 18th on the subject of exchange of information between the A.P.I., and the Groups concerned over here in studying the carcinogenicity of petroleum. you may care to make a Alco Products Inc., SO This is very timely aa I shall be arriving in New York on the 16th April and shall American continent for about three weeks after therefore like to come and have a talk with you I am not certain what actual date to suggest. in touch with you on arrival and fix a date. I note that I can be contacted c/o Mr. Manuel Alonso, Church Street, New York. 8 N.Y. U.S.A. C W U J 1- o Yours very truly, CpJLUJ - ^ SJMA/gbm API 06355 I 711e: MAC C o lco o l 8 J . Um aAm 26 T H a i Roo* Late, Um U , tagloa Door Colanol 8UU Is wo houli Ite otll S t o m t e oooi i, i & r Z. P DfBtJO API 06356 u niversity of Gla s g o w Department el Public Health and Sedai Medicine professor pino! Ftriusoo 4 University Gardena Glasgow, W .2 Telephone: KoMn 2331 AIR MAIL 21st June, 1957. Dear Mr.Stroop Thank you very much for your note. Dr. Norton's address is 38 Old Qaeen Street, Westminster, London, S.W.I., and I have written to him following Col. Auld's letter to me. Yours very sincerely, D.V. Stroop, Esq., Executive Assistant, American Petroleum Institute, 50 'West 50th Street, New York 20, N.Y., U.S.A. API 06358  4 'Irt/*: /s* o Esso Research and Engineering trO K M U LT ttAMDAHD OIL DTYKLOPUtNT COMPAM I) P. O. BOX 131, LtM ttBM . N. J . Company MEDICAL RESEARCH DIVISION omic'oi* O t t C f V T C L C X A I O T P H O M O N V H C N JK tC K I H ( A O I N O U I ' R I A L <> . . A, "H. r MOAACE W OERAROC Ah O M O m c a o rokickOC'A* B E R T R A N D C. B E N N lB O N M O e * i r c c ia ic a a . a c i b a r c n *** i* n Mareh 11, 1957 Copy Pro D. ? Stroop Por Information Of Nedbert Of MedioaX'ASvlory CoMritte 3/18/57 Kr. D, T. Stroop Anerican Potroloaa Institut 50 Voit 50th Stroot Iv York 20, 1 York Sort Kr. Stroop* I m aending yeo oopiea of 11 tho niante f the Sabeeaaltteo m CarelaofaBlclty for the yorB 1955-1958 in rompons to joor roqpost of Maroh 6, 1957* Zn additlan, I an adne yoa m m lafanation obtalned frai tho Modloal Boaoareh Cooncll in Britaln thio) prbbably oaght to b dsplieated and dietribatod, t loaat to tho flubnc-- lttoo aaahf nd to th grosp t Kattarlag Laboratory. Piaally, I do not boller thon ia ny mah to raprodaoo tho Brltiah port ofaleh joo noatlonod in yoar lattar and I m aaro job ean do thia et yoar liaaro. Sinearoly yoara, I. S. SCKABDf, K. D. ^40 BEStcjh Attach. - Klaatoa of tha Coaad.ttao an the Carcinofoie Aotloo of Klnaral Olla of tho Xodieal Boaeareh Coandi. MRC.57A 76 ClM0.Xia.21. - Bapert of tho SabceMoltto on Carcinogonicity to tha Modloal Adrieory Oonitt datod Aprii 25, 1955. - Bapert of th Sobco^dtt on Carclnoganicity to th Modloal Adrisocy Ooanitt* datod Oetobar 11, 1^55. - Bapert of tho Saboooslttoo on Caroinoffloielty to tho Hodieal Adriaocy Ccaadtt datod Aprii 23, 1956. - Minato of tho Sahioo-- dita an Careinoganieitgr fer thair aaotiag on Saptoabar 6, 1956. - Propoaad Bapert of tho Saboonaittoo on Careinoganieity to tho Modloal Adrlaox: Caaalttaa fer ita Meeting on loroabor 12, 1956, datod lorantoor 5, 1956. X&etatod, bat not rd API 06359 ycrt For Publication, For Information Only Of Members Of The Medical Advisory committee MEDICAL RESEARCH COUNCIL "Unclassified" For Specified Circulation "[Members of Committee) MRC.57/176 CAMO.Min.21 COMMITTEE ON THE CARCINOGENIC ACTION OF MINERAL OILS Minutes of the twenty-first meeting held at 38 Old Queen Street, London, S.w.l, on Tuesday, lth December, 1956 at 2.30 p.m. Present:- Professor T. Ferguson (Chairman), Col. S.J.M. Auld, Dr. J.W. Cook, Dr. I. Hieger, Dr. J.O. Irwin, Professor F. Morton, Professor R.D. Passey, Professor J. R. Squire, Dr. D. L. Woodhouse, with Dr. R.C. Norton (Secretary). Attended: Dr. Philip J. King, and Dr. W. Carruthers. An apology for absence was received from Professor H.N. Green. 1. Minutes Dr. Irwin suggested that the Minutes of the previous meeting might be amended by re-numbering the paragraphs under item 3, "Progress Reports", so that they agreed with the numbering of the corresponding items of the agenda for that meeting. The numbering of the paragraphs under min.3, of the twentieth meeting should therefore be as follows:- Min.3.(a) by Dr. W. Carruthers and Dr. J. W. Cook (MRC.56/5^3, CAMD.56/k) to be re-numbered 3*(i)(a), Min.3*(b) by Professor F. Morton (CAMO.56/7 ) to be re-numbered 3*(i)(b)> Min.3.(c) by Dr. D.L. Woodhouse - Progress Report No. XVI (May 1956), (MRC.56/5^2, CAMO.56/3) to be re-numbered 3*(ii)(a), Min.3.(d) Data tables on mineral oil fractions, submitted by Dr. D.L. Woodhouse (CAMO.56/3) to be included in 3(ii)(*0> Min.3.(e) Experiments with mice at Leeds (MRC.56/5^8, CAhO.56/5 and MRC.56/5^9, CAMO.56/6 to be re-numbered 3-(ii)("b) and (c). It was further suggested that in the first line of paragraph 3*(c) in the Minutes (before amendment) of the previous meeting the word 'importance' should be substituted for 'significance'. The beginning of this paragraph should therefore read "Dr. Irwin said that a point of great importance emerging from the report was the failure .... " The Committee agreed to these amendments and the Minutes of the twentieth meeting were then signed by the Chairman. 2. Matters arising 06360 professor Squire said that he had now heard from Dr. W. E. Smith (Min.2 of the 20th meeting) who was anxious to carry out further tests by his rapid screening -2 - method of oil samples already tested under the Committee's programme. After dis cussion it was agreed to send Dr. Smith further samples, although any results which he might obtain would not be likely to be of great assistance in the present phase of the Committee's programme. In this connection Cel. Auld suggested that it was desirable to build up a more direct association with American workers in the field and it was agreed that he and Professor Morton should investigate further methods of doing this. 3* Progress Reports (a) No.XVII, November 1956 (Birmingham), by Dr. D.L. Woodhouse, Tm r c V56/9^6. CAMP.56/9).----- -- ------------------ Dr. Woodhouse gave some further figures for the incidence of tumours at k2 weeks in his series of rabbit tests. These were for each fraction shown in Table I:- (A) 2 (B) 0 (c) 0 (D) 1 (E) 1 (F) 3 (G) 0 (H) 0 (1 ) 0 (J) 1 (K) 0 (L) 1 (M) 1 (N) 0 (0) 7 (P) 7 (Q) 7 (R) 8 (s) 5 (T) I k (u) 8 He also said that in Table II 'Mouse tests', fraction (T) D(2) should read D(i) and that fraction (ll) D(j) should read D(). Since fractions A-E (vith parent fraction L) and F-H (with parent fraction M) were more active than I-K (vith parent fraction N), these results showed that chromatography on alumina is a promising method of separation, the active substance(s) being eluted by petroleum ether (A to E + L), though some remained for subsequent elution with benzene (F to E + M). (*>) The 1955-56 Experiments with Mice at Leeds, by Dr. J.O. Irwin, (MRC.56/965, CAM0.56/I2T: Dr. Irwin pointed out that with the standard D2 at Leeds, tumours had oc curred much later than ejected. There also appeared to be a small, but genuine dif ference between the potency of the L and K series. It was noted that in the second sentence of the last paragraph of the first page f()this paper, the first "D2" should read "d " so that the whole sentence should read: "However, DJ at Leeds in 1955-56 gave a lower response than d at Birmingham in 1953-*+ and D2 at Leeds gave a much lower response than D2 at Birmingham in the same year." Commenting on the statistical analysis of the 1955-56 ejqperiments with rabbits at Leeds (MRC.56/969, CAMO.56/13), Dr* Irwin drew attention to the unusual number of tumourless deaths, and, referring to the standards, he said that D2 appeared to be normal but that the results with had been unusual. Again the L. series appeared to be slightly more carcinogenic than the corresponding K's. In both papers the fractions referred to as L^SR and K^SR should be L^SP and K^SP respectively, and when referred to in the text the word 'raffinate' should be substituted for 'residue'. API 06361 - 3- (c ) Report fry Dr. W. Carrutbers, Dr. J. W. Cook and Mr. A. G. Douglas, (MRC.56/95, CAM0.5b/lfT Dr. Carrutbers introduced his Report fry remarking that attempts to isolate homogeneous compounds from the Kuwait picrate-forming fractions were continuing. A synthetic programme based on the results so far obtained was about to be started. The 6:7-benzothionaphthene derivative discussed in his Report was the first example of this particular ring system to be detected in mineral oil. It now seemed desirable to do tests for carcinogenicity on some of the pure compounds isolated; it was agreed to include several in the 1957-58 Birmingham tests if adequate amounts could be provided. 4. Preparation of Kuwait fractions for 1957 to 1958 tests (MRC.56/956. CAMP.56/10). Professor Morton said that he had tried to find suitable areas in which to carry out the plcrate separations with his own resources, but that he bad been un successful. He had therefore approached several commercial firms in an attempt to get them to carry out the separations, but they had been unwilling to do so. He therefore proposed that as the best possible alternative in the time available he should try to provide separate fractions from IQ* and KXg.8 by chromatography carried out in his existing laboratory. He hoped to have completed this stage by the end of February and it was agreed that he should hold a discussion with Professor Squire and Dr. Woodhouse in early March to work out details for the next stage of the work at Birmingham. He confirmed that he would be able to provide the necessary 12 fractions fry that time. It was noted that Professor Morton would include in the samples for testing a friend of eluates as well as original material in an attempt to account for the apparent loss of carcinogenicity noted at the previous meeting. In view of the results on the spinning band column, Professor Morton said that he was now building the equivalent of a molecular still - a 'spinning brush' column - which was capable of operating at pressures down to 0.2 mm, which enabled the work to be carried into a boiling range which had not hitherto been looked at. He was proposing to supply Dr. Carruthers with specimens of Ki*So and K^X^. He also reported that he had received-^500 from I.C.I. for the installation of a Vapour Phase Chromatographic Column to work at temperatures of about 300C, which would enable separations to be made in the middle range of residues. 5. Proposal for including in the Birmingham tests a single specimen of cutting oil, reported to be non-carcinogenic. Professor Squire said that he had heard of the oil prepared fry Manchester Oil Refineries which according to the Twort Formula was said to be non-carcinogenic, through an informal letter from Dr. Schilling. It was proposed that a sample of this oil might be included in the 1957 to 1958 tests. After discussion it was agreed that the inclusion of such an oil might in volve the Council in difficulties with other commercial firms producing similar oils, and it was felt that before the proposal could be considered further a case must be made out for doing so as part of the normal scientific programme sponsored fry the Com mittee. Dr. Norton pointed out that there were precedents for the Council undertaking such tests on the products of commercial firms, but that they were always done on the API 06362 -U condition that the results obtained would not be the exclusive property of tne in dividual firm and that they could be freely published. An alternative method whereby the oil in question might be tested would be for a request to this effect to be sent to the Council through B.M. Inspectorate of Factories. Professor Squire said that he would consider the matter further in view of these procedural difficulties and it was agreed to defer consideration of the matter until he had done so. 7. Date of next meeting It was tentatively suggested that this might be in July 1957, but that a final decision would have to be deferred until the meeting between Professor Morton, Professor Squire and Dr. Uoodhouse proposed for the beginning of March (MinA) bad taken place. API 06363 _ -t~. '.c ESSO RESEARCH AND ENGINEERING COMPANY (FORMERLY STANDARD OIL. DEVELOPMENT COMPANY) P. O. Box 121. L i n d e n . N. J. m edical r e s e a r c h d iv isio n 0OBERT e ECKAROT PH O M O OlftCCTO* N v HEN DRICK S C m E h (A O INDUfTHIAL H V O IIN ItT HORACE W GERARDE PH D M D ggR TRA N D E BEN N ISO N M D c h ief c l in ic a l A tSlA K C M am v sicia n Kerch II, 1957 Copy Proa D. T. Stroop For Information Of Meabere Of Medical Advisory CoHdttee 3/18/57 Mr. D. T. Stroop laericen Petroleam Institate 50Vert 50th Street lev Toxic 20, lev York Dear Mr. Stroop I at leading job oopiee of all the ainatea ef the SabeoHdttee ea Carcinogenicity far the Tears 1955-1956 In response to year reqeest of March 6, 1957* In addition, I m leading yon son* infemotion obtained fren the Medieal Research Cevnell in Britain vhieh probably ovght to be duplicated and distribvted, at least to the Saboosnittee nenbvrs and to tho groap at Kettering Laboratory. finally, I do not bellero there is any rash te reprednoe the British report vhieh yea aantionod In year letter and I m sere yea can do this at year loisare. Sincerely years, R. X. XCEABOT, M. D. , BEXtcJh Attach. - Minatea of tho Ccaaittee on the Carcinogenic Action of Mineral Oils of the Medical Research Ceandl. MRC.57A76 CAMOJUn.21. - Report ef the Sabecanittee on Carcinogenicity to tho Medical Advisory CcmdLttee dated April 25, 1955. - Report ef the Sahninrlttoe on Cax*cinogenicity to tho Medical Advieoxy Cooed.ttee dated OeWber 31 1555* - Report ef the Saboosnittee on Carcinogenicity te the Medieal Advisory Connitteo dated April 23, 1956. - Minateo of tho Sahmwittee on Carcinogenicity for their noeting on Septanber 6, 1956. - Proposed Report of the Sabend.ttee on Carcinogenicity to tho Medieal Advisoxy CojocLttee for its Meeting an lovenber 12, 1956, dated lorohber 5 1956. Dictated, bat not read API 06364 r MEDICAL RESEARCH COUNCIL "Unclassified" Per Specified Circulation (Members of Ccnrittee) :sc. 57/176 CAMC.Min.21 COC'MTKU cr ^ CAUCUTOGEflC ACTION CP MINERAL O H S Minutes of the twenty-first meeting held at 3 8 Old Queen Street, London, S.W.l, on Tuesday, lfith Decssber, 1958 at 2.30 p.m. Present:- Professor T. Ferguson (Chairman), Col. S.J.M. Auld, Dr. J.W. Cook, Dr. I. Hieger, Dr, J.O. Irwin, Professor F. Morton, Professor H.D. Passey, Professor J.R. Squire, Dr. D.L. Woodhouse, with Dr. R.C. Norton (Secretary). Attended: Dr. Philip J. King, and Dr. W. Carruthers. An ariolo^v for absence was received from Professor H.N. Green. 1. Minutes Dr. Irwin suggested that the Minutes of the previous meeting might he amended by re-numbering the paragraphs under item 3, "Progress Reports", so that they agreed with the nunhering of the corresponding items of the agenda for that meeting. The numbering of the paragraphs under min.3, of the twentieth meeting should therefore be as follows:- !!in.3.(a) by Dr. W. Carruthers and Dr. J.W. Cook (MRC.58/543, CAMO.58/4) to be re-numbered 3.(i)(a), Min.3.(b) by Professor F. Morton (CAMO.58/7) to be re-numbered 3-(i)(b), Kin.3*(o) by Dr. D.L. Woodhouse - Progress Report No.XVI (May 1958), ' (m r c .5 6 /5 4 2 , c a m o .56/3) to be re-nuaibered 3.(ii)(a), Min.3.(d) Data tables on mineral oil fractions, submitted by Dr. D.L. Woodhouse (CAM0.58/3) to be included in 3.(ii)(a), Min.3.(e) Experiments with mice at Leeds (MRC.58/54S, CAM0.58/5 and :C.56/5i*.9, CAMO.58/6 to be re-numbered 3.(ii)(b) and (c). It was further suggested that in the first line of paragraph 3.(o) in the Minutes (before amendment) of the previous meeting the work 'importance' should be substituted for -significance'. The beginning of this paragraph should therefore read "Dr. Irwin said that a point of great importance emerging from the reoort was the failure ..... " The Committee agreed to these amendments and the ?!inutes of the twentieth meeting were then signed by the Chairman. 2. Matters arising Professor Squire said that he had now heart fran Dr. W.E. Smith (Min.2 of the 2Cth meeting) who was anxious to carry out further tests by his rapid screening^piethod of oil samples already tested under the Committee's After discussion it was agreed to send Dr. Smith further saaples, although any results which he might obtain would not be likely to be of great assistance in the present phase of the Ccnnittee's programme. -r ccmccticr. -ol. A u l d suggested that it was desiraele to build up a'scr-; direct association witr. American workers in the field and it was agreed that he and P r o f e s s o r Morten should investigate further methods oi1 Icing thi3, 3 . Progress Reports (a) Vo.XVTI. November 1956 (Birmingham), bv Dr. D.L. Toodhouse, (: 3 C . 5/94b,'CAVO.5 6 / 9 ) . ......... Dr. Woodhouse gave some further figures for the incidence of tumours at U2 weeks in his series of rabbit tests. These were for each fraction shown in Table Is- (A) 2 (w c) 0 2 (D) 1 IH) 0 I) 0 J) 1 K) 0 10} 7 P) 7 Q) 7 R) 8 (3) 1 F) 3 (g) 0 L) 1 M 1 N) 0 S) 5 T) 14 8 u) He also said that in Table II 'House tests', fraction (T) D(2) should read D( 7 ) and that fraction (U) D(5 ) should read D(i). Since fractions A-E (with parent fraction L) and P-H (with parent fraction V) were more active than I-K (with parent fraction N), these results showed that chromatography on alumina is a promising method of separation, the active substance(s) being eluted by petroleum ether (A to E + L ) , though some remained for subsequent elution with bensene (F to H + M ) . (b) The 1955-56 Sxperiments with Mice at Leeds, by Dr, J.C. Irwin, (M R C .56/965 CAM3.56/121) " Dr. Irwin pointed out that with the standard D- at Leeds, tumours had occurred much later than expected. There also appeared to b e a small, but genuine difference between the potenqy of the L and K series. It was noted that in the second sentence of the last paragraph of the first page of this paper, the first "D." should read "d " s o that the whoh sentence should read: "However, Djr at Leeds in 1955-56 gave a lower response than at Birmingham in 1953-4 and D_ at Leeds gave a much lower response than D 2 at Birmingham in the same year." Commenting on the statistical analysis of the 1955-56 experiments with rabbits at Leeds (MRC.5 6 / 9 6 9 , CAMO.56/13), Dr. Irwin drew attention to the unusual number of tumourless deaths, and, referring to the standards, he said that D. appeared to be normal but that the results with D ? had been unusual. Again the L. scries appeared to be slightly more carcinogenic than the corresponding K's. In both papers the fractions referred to as l^SR and K^SR should be L 4SP and Ma SP respectively, and when referred to in the text the word 'raffinate' should be substituted for 'residue',J^> (c) Report byar.TT.Carruthers, Dr. J.W. Cook and Mr. A.G. Douglas. CIRC.5 6 / 9 5 5 7 CAMP. 56/111. Dr. Carruthers introduced his Report by remarking that attanpts to isolate homogeneous compounds from the Kuwait picrate-foiming fractions were continuing. A synthetic programme based on the results sc far obtained was about to be started. - 2 - :ie te _eld ar. ther oe of or each T) D(2) ith parent neae results paraticn, I) , though tumours a snail, ragraph of chat the whole wer response response xp e n m e n ts rer.tion to ar.dards, he ai been r .::5 a o th a n 3R should be The o:T-ber.oethicr.arhtr.ene aeri' itivc -- trussed in his Report was the first example of this particular ring system to be detected in mineral oil. It now seemed desirable to do costs for carcinogenicity on sene of the pure compounds isolated; it was agreed to include several in the 1957-58 Birmingham tests if adequate amounts could be provided. Preparation of Kuwait fractions "or 1957 to 1958 tests. (;aC.5/95. 1A.MC.56/5T! Professor Morton said that he had tried to find suitable areas in which to carry out the picrate separations with his own resources, but that he had been unsuccessful. He had therefore approached several caanercial firms in an attempt to get them to carry out the separations, but they had been 'xrrilling to do so. He therefore proposed that as the best possible alternative in the time available he should try to provide separate fractions from K, and KXg_g by chrcmatograpty' carried out in his existing laboratory. He hoped to have completed this stage by the end of February and it was agreed that he should hold a discussion with Professor Squire and Dr. foodhouse in early March to work out details for the next stage of the work at Birmingham. He confirmed that he would be able to provide the necessary 12 fractions by that tine. It was noted that Professor Morton would include in the samples far testing a blend of oluates as well as original material in an attempt to account for the apparent loss of carcinogenicity noted at the previous meeting. In view of the results on the spinning band column, Professor Morton said that he was new building the equivalent of a molecular still - a 'spinning brush1 column - which was capable of operating at pressures down to 0.2 nm, which enabled the work to be carried into a boiling range which had not hitherto been looked at. He was proposing to supply Dr. Carruthers with specimens of K^Sq and KvXj. He also reported that he had received 500 from I.0.1 for the installation of a Vapour Fhase Chromatographic Column to work at temperatures of about 300 C, which would enable separations to be made in the middle range of residues. 5. Proposal for including in the Birmingham tests a single specim-- of cutting oil, reported to be non-carcinogenic, Professor Squire said that he had heard of the oil prepared by Manchester Oil Refineries which according to the Twort Formula was said to be nonoaroinogenic, through an informal letter from Dr. Schilling. It was proposed that a sample of this oil might be included in the 1957 to 1958 tests. After discussion it was a? led that the inclusion of such on oil ni.v.t involve the Council m difficulties with other commercial firms producing similar oils, ar.d it was felt that before the proposal could be considered further a case must be made out for doing sc as part of the normal scientific programme sponsored by the Committee. Dr. Horton pointed out that there were precedents for the Council undertaking such tests on tr.e products of commercial firms, out that they wsrc always done on thc^cor.dition that the results obtained would not be the exclusive property of the individual firm and that they could bo freely published. on alternative method whereby the oil in question might be tested would be for a request to this effect tc be sent to the Council tnrough H.H. Inspectorate of Factories. Professor Squire said that he would consider the natter further in view of these procedure.- difficulties and at uas agreed to defer consideration of the matter until he had done sc. 7. Date of next meeting It was tentatively suggested that this might he in July 1957, but that a final decision would have to be deferred until the meeting between Professor Morton, Professor Squire and Dr. Woodhouse proposed for the beginning of March (Min.4) had taken place. 2r in ieratio^ "but sen Esso R esea r c h and E n g in e e r in g Com pany (PORMIMLY STANDARD OIL DEVELOPMENT COMPANY) P.O.BOX 45.LINDSM.N.J. MEDICAL RESEARCH DIVISION R O S C P T c. CCKAftOT. P M O .M O. OIMSCTOP C n n iA N O K. M N N I tO N M D ASSItTANT OfltCeTOfi N. V H K N D H ie K t. CM. C. HEAD inouvtimaw MV4MVNWT H O M A e t W O C M A H O I . PM. O .M O M|AO rOllCObMWT taw a, 1957 Mr D. V fttroop JnsrieB Petroleue Inert!tut 50Vut 50tM fltroet Mow York 20, Kv York Om t Mr Mtroopi 1 m Attaching m m information forwrded to as t r m Or. M I. lomqoiat tgr Mr. A 1 Doolsgr. Pocrtupe 700ooold Ilk* to hero tide doplicated and distributed to tbe Pife o the fluboouattee ob CtfelaogMleltT end leo to Or Horton and Dr Kaboe. fliaeoraly y w t E *. ttSAEDT, M. D. ^ HBtcjh _ Attach. - Institut of Patrolaoa. Boeaarob (from lo. 2. Minuta# of Meatinf Mo. 17 bald at 26, Portland Piaos, .1. ob tbs 12.3.57 Copy Pro D. V. Stroop For Information Of Members Of Subcommittee an C a r c i n o g e n i c i t y 6/20/57 INSTITUTE OF PETROLEUM RESEARCH GROUP NO. 2. Minutes of Meeting No. 17 held at 26, Portland Place. W.l. on the 12.3.57. ATTENDANCE IN THE CHAIR: F. Morton MEMBERS: S.J.M. Auld G .A. Dickins J.N. Haresnape C.F. McCue H.W. Stevenson APOLOGIES FOR ABSENCE: B.G. Banks J.W. Barrett J.W. Cook A. McLean SECRETARY: E. Herbert RES-2- 1. MINUTES OF MEETING NO. l6. 23.10.56: These were signed as correct, subject to the addition of "pages 1L6-155" "The Transactions of the Institution of Chemical Engineers" Vol. 3^ No. 2. (See Minute No. 7) and the alterations of "Research No. 2 Committee" :o "Research Group No. 2." 2. MATTERS ARISING: (a) The Chairman mentioned that the paper for publication in the IP Journal i continuation of that presented at the World Petroleum Congress had been prepared ( Minute 3 of Meeting 15). (b) The disappearance of activity referred to by Dr. Irvin was being studied the present series of tests at Birmingham (See Minute No. 5 and Minutes No. h para. 2 of M.R.C.^Minutes M.R.C.57/176 and C.A.M.O. Minute 21). 3- CONSIDERATION OF FINANCE FOR FUTURE PROGRAMME: The Chairman's memorandum and the report on the Constitution and Biologic Activity of Mineral Oils which had been circulated va6 noted. The Chairman mentioned that there was no great urgency for additional fin. cial support as the I.C.I. and the Salter Research Institute had made contributions ;^_500 each and the M.R.C. Current Budget included a grant similar to that made lasyear. It appeared that there was sufficient finance available to complete the pres' work. During general discussion, it was evident that development of methods was of more interest to industry than actual results and that a biological testing unit fouse of industry would be welcome. The Chairman undertook to prepare a memorandum o: suggestions for future work which would include (a) programme for Middle Distillate: and (b) Oxidation. API 06370 - 2 Members were asked to write their comments to the Chairman after considera tion of his memorandum so that recommendations which were likely to receive industry's financial support could be forwarded, through the Research Committee, to IP Council early in 1958* 4. DATE OF NEXT MEETING; To be arranged by the Chairman. May, 1957. JB. API 06371 L. Esso Research a n d E n g in e e r in g (FORMEi\~Y -7 A S l 'xD v.L D El'ELO P M EN T COMPANY) P.O.BOX 4YLI.VDEN.N.J, Company MEDICAL RESEARCH DIV'SION 0 R O B E R T E E C K A R D T P H O M 2 'C C T O BERTRAND E BENNISON M D A SSIST A N T O'A CCTOP N V H E N D R IC K S CM E HEAD INOUSTRIAL HYGIENIST HORACE W GEPARDE PH O M D h Ca o toxicolOois' Jxme 21, 1957 Mr. D. V. Stroop American Petroleum Institute 50 West 50th Street Nev Tork 20, Nev Tork Dear Mr. Stroop: I am attaching sane information forwarded to me from Dr. M. N. Newquist by Mr. A. E. Dooley. Perhaps you would like to hare this duplicated and distributed to the members of the Subcontri,ttee on Carcinogenicity and also to Dr. Horton and Dr. Kehoe. Sincerely yours, "/p. R. E. ECKAHDT, M. D. RE:cjh Attach. - Institute of Petroleum. Research Group No. 2. Minutes of Meeting No. 17 held at 26, Portland Place, W.l. on the 12.3.57. Copy From D. V. S tro o p For I n f o r m a tio n Of Members Of Subcommittee on C a r c i n o g e n i c i t y 6/ 26/57 API 06372 * 17 h eld -t 26, Port'. 1 2 . 3 . 5 7 . ________________ "RS; ..FOLOGIES FOR ..3SEMCE SECRETARY F. N o r t o n S . J . H . ..uld G.... Die k i n s J.N. Haresnape C.F. Mo Cue K Sts von son B .G . 3r. nks J.3arrott J.M. Cook Me L e o n Herbert 1. M I N U T E S O F M I S T I N G NO. 16. 2 3 . 1 0 . 5 6 ; Th o s o w ? r e signed as corroot, subject t: the - d i e t i o n of 11png os 1 4 6 - 1 5 5 " to "The Tr e.nsnct i o n s of t h e I n s t i t u t i o n of C h e m i c a l E n g i n e e r s " Vol. 34 No. 2. (See Minute No. 7) red the e l c c r e t i o n s of'lRosc'rch No. 2 C o m m i t t e e " t o 'ftosearch G r o u p No. 2. 2. M A T T E R S . . R I S I N G ; (a) T h e C h a i r m e n m e n t i o n e d the.t the p e p e r f o r tn.o IF J o u r n a l in c o n t i n u a t i o n of t h a t p r o s o n t o d Pctrolcun Congross had been prepared (Soo Minute p u b l i c a t i o n in at th e V.'orld 3 oi M e e t i n g 15) (b) T h e d i s a p p e a r a n c e of a c t i v i t y r o f e r r o d t o b y Dr . I r w i n vies b e i n g studied in t n e p r e s e n t s e r i e s of t e s t s e.t Eirre.ingh.-m (See H i n u t o No. 5 and M i n u t e s No. 4 para 2 of M.R.C. M inutes M . R . C . 5 7 / 1 7 6 n n d c ** M .O. M i n u t e 21 ). 3. C O N S I D E R A T I O N O F FIN..NCZ F O R F U T U R E FR0GR..rES; and was The C hairman's reemorandum and the report on m e B i o l o g i c a l h e t i v i t y of M.ln'ral Oils w h i c h and tecn notod. Constituti circul-tcd The Chairmen mentioned that there was no greet urgency for additional financial support as the I.C.I. and tnc Salter R e s e a r c h I n s t i t u t e had made c o n t r i b u t i o n s of 5 0 0 c a m . end the M.R.C. Current 3udgot included a gr*nt simil-r to that made last y e a r . It a p p e a r e d t a r t m a r ; v:~s s u f f i c i e n t f i n a n c e a v a i l a b l e t o c o n p l o t o th e p r e s e n t w o r k . D u r i n g g e n e r a l d i s c u s s on, it '.'.'as e v i d e n t t.aet d e v e l o p m e n t of m e t h o d s w a s of m o r e i n t e r e s t t o i n d u s t r y t h e n r c t u - 1 r e s u l t s -nd tr.-t - b i o l o g i c a l t e s t i n g u n i t fo r u s o of i n d u s t r y w o u l d oc vielcome. T h e C h a i r m e n u n d e r t o o k t o p r e p a r e " m: mur - nd urn of s u g g e s t i o n s f o r f u t u r e w o r k w h i c h v.ould i n c l u d e d (a.) p r o g r a m m e f o r M i d d l e D i s t i l l a t e s and (b) O x i d a t i o n . - 2- Members were nshed t o w r i t o t h e i r comments t o Che C--eirman a f t e r c o n s i d e r a t i o n of h i s memorandum so t .'.:.t recommendations which were l i k e l y to receiv e i n d u s t r y 's f i n a n c i a l s uppor t could be f o r w a r d e d , through, t h e R o s e - r c h Committee, t o I? Council early in 1958. of nzkt m i s t i n g : To be a r r a n g e d by t h e Chai r man. he 7, 1957. JB. I i API 06374 film me / i A ' wm ai m i ft. lb ) API 06375 o tz t K.o. o c wt/c- \ C .C ^7e_ C t-J-**/juusX*(rJ y ~ \-J<vCv y -- -Ju u J. o^w A ; O C ^ / g . L .E .C a n t e K .D . ' ^ j l L ^ - Q i , ? . C *vi fec / * CafAJovwCUj^ trvJ i|u\. 0 AiHCAAV-^ t M M ( ^^fW f D o / i A 1)dLfl.gJJ-tcj 0 a ^ A/oCuffi S S OSA Q J A <VL , L-&->lJLg"YV \Jj sYx>A*.v&. -X^-g-tOL cHx i A J u U M Ai.^ j 3 * vXbJL 0~*V- Jiht^yr^ ' C*-~v/vvC3C. <ro^>JJU*><ryvv^^ u - ^ P X - A A j iD iM w S i i 9 S \ - __________ *o.JC G ^ ^ ^ g t c ^xcfccj( Q t K J 2 ^ 5 ((& 4 r ) ^V^LsaJ C J m ? t \ ) Q Lj c U S - jl * G u oe> i 1 (o je , JZj u API 06376 ^ ^ Q-^C-4-**o-~| Qrw~~"^fc-- ^ j-'frPX. >K zT(u w /^lav ^ Ie?i X 4 ^ t f r rL._ \ A --. ___ 3Bt \ a -fct/ Ct^A+ul ? p ^ - T 2 __ r " y J+ fc * A *-- E j'i^ v 'f'- A 'P I (2a> * ~ jLi f L t y ^ J - h jC ~ / O / /fy^ % . J yCtwv-- *) J ^ iix-t - / V P X l 2 x M M ^ V . <v p t ( 2 i^ w L f^J t '\ \ / C K L * a A j iA 0 n m _ ^ u _io fc^SdA^- O n K ^ , w x ______ XxX-v-^ ^ ^ ^ --o ^ >L^ * vV *------------cL. API 06377 to API 06378 exhibit a TO MIHUTgS CF MEETING OF MEDICAL ATVISCRY CCMMITTEE April 25, 19 5 5 REPCRT OF TEE SUBCOMMITTEE ON CARCIIiOGEHICITY Robert E. Eckardt, M. D., Chairman_____ I. statue of Publication The nanuscript on the method of determining benzpyrene la published. A alight modification of the method, which la attached as Appendix A, will be attached to reprints of this publication. The manuscript on Carcinogenesis of the Skin was returned to Kettering Laboratory with suggestions for condensation of portions of the paper, and expansion of the Introduction so It will have more meaning to cancer research workers. This expansion of the Introduction and other modifications Is attached as Appendix B. II. Status of the Biological and Chemical Work The interim report of the Laboratory is attached as Appendix C. The original concept that petroleum products in the boiling range of 1*50-650? or 7007 all contained significant quantities of accelerators now appeals untenable. Rather it appears that in this range, there are variations in accelerator content which the laboratory is now in the process cf working out. It is felt by the laboratory that this is important because a comparison cf mouse data with available human data, suggests to the laboratory that accelerators may have significance in human skin carcinogenesis. This may be even more important in the petroleum industry than the coal tar industry. Work to date suggests that petroleum cuts boiling in the range 625-650? may be low in their accelerator content. On the other hand, above 650? there appears to be another surge of accelerators. Present work also suggests that alkyl naphthalenes are very potent accelerators, far more so than straight chain paraffins. Furthermore, they may not be as easily reduced in their activity by dilution as the straight chain paraffins. Washing experiments suggest there is no advantage, and possibly a dis tinct disadvantage to using a petroleum material as a rinse prior to washing. III. Future Chemical and Biological Work About 55)1 of the effort of the laboratory in this direction will be in chasing down the nature cf the carcinogens in the 700-725-750 ? boiling range. To date 3 classes of carcinogens have been identified: (1) Benzpyrene types, (2) Types which form an adduct with maleic anhydride, presumably benzanthracenes, and (3) the as yet unidentified types in the 700-725-750 ? range. About 35% of the effort of the laboratory in this direction will be de voted to separating and characterizing the properties of accelerators. For this, boiling range, gravity, refractive index and mlllne point have been API 06379 found tc be useful tools. will be Investigated. - 2 - Liquid tbernal diffusion as another useful tool To date four types of accelerators are known: (1) straight chain paraffins, (2) Alkyl benzenes, (3) Alkyl naphthenes and (W) Alkjrl naphthalenes. It appears that there is a chain length in each type which gives optlima accelerating properties. Further work on the definition of optimum chain length is planned. From what has been said, it is evident that accelerators are major components cf petroleum. In contrast, carcinogens constitute only minor components. XV. Epidemiology A progress report by Or. Phalr is attached as Appendix 0. $00 new cases have been reported, bringing the total to 1800. The data on all 1800 of these are now being transferred from the previous manual sort cards to electronic sort cards. It is anticipated that this transfer, and Initial correlations will be available by the next meeting of the Medical Advisory Comolttee. It is possible that preliminary incidence figures will also be available at that time. Ifce medical directors are again encouraged by the subcommittee to con tinue and extend whenever possible, their reporting cf cases to Dr. Phalr. V. Budget The budget for July 1, 1955 to June 30 1956 is $65,000, to be expended as follows: Biological Work $20,000 Technical Work 32,250 Epidemiological Work 12,750 The subcommittee has requested of the Kettering Laboratory that a complete status report of the work be prepared in advance of the next Medical Advisory Cosmdttee Meeting. This status report should include significant conclusions of the work to date, with supporting data, grouped in accordance to important individual conclusions. In addition, a brief outline of future objectives should be Included. Reccf nrtstlon: The Subcoonittee recommends that this work be continued with a budget of $56,500 for the period July 1, 1956 to June 30, 1957. Of this budget, from $15,000 to $20,000 shall be expended in the epidemiological work. April 25, 1955 API 06380 U . r? J j \ _____ >, PROPOSED REPORT OF THE SIBCCMCHEEE CS C;jyiBUZ3gCmf 'v.__ TO TH2 MEDICAL AJV13QRI COKHTE2 for Its neeling on Bowser 12, 195-* to be held at the Conrad Hilton Hotel In Chicago a/c j * Z"12* Recent newspaper publicity concerning the carcinogenicity of axes which ay be used on Bill certooe, have lead the 8ubconnittee on Carcinogenicity to consider it advisable to oooduct biologlcel testing which will help eetehUah the no-carcinogenicity of wane. In addition, it la the belief of the 8\>eomlttee on Carcinogenicity that wane, other then carton wans which night also be used In the food industry, 1 be included in this testing progra in order to develop a acre complete picture of the situation concerning wens. In view of this, the subeonlttee the following courses of action to the Mdlcal Advisory "mitt m i 1) A survey of the types of wans which are used in the food industry should he undertaken In order that a oc^>lete understanding of the types of wens which ccm In contact with food can be bad by the siiTinrall tea 2) Pollening the abora survey a selection of csqplee fraa these vans should be nda in order to provide a potential rangs of oarcinoganle activity in tha wens annulled, which will be detarsdnsd by the follmrlng factors: API 06381 * -s - a) The crude source. b) Tam oil contest. e) The degree esd type of refining. 3) The reliable biological aetbode ror car cinogenic testing of aaterlals, colorable to waxes which find their way into food usage, should be reviewed and fro* thee a selection of biological aetbode to be used in the testing progrsa should be aade, but these should probably includet s) Feeding. b) Skin appllextlooe. 4) The sibcaaaittee hss received free Dr. Kabos, eft the Kettering laboratory, a proposal for such studies. However, tbs subecanlttee does not believe that Dr. Ssboe's proposal Is wyiletoly realistic with tbs prbblea being faced coneerning wax carcinogenielty and, therefore, requests approval of tbs Medical Advisory Ccenittee to survey other toxioological laborattoriee far their prapoeels eoncerning carcinogenicity, their facilities for con ducting such tests sad their budget vetlaatee on the costs of such tests. Such laboratories to be surveyed. API 06382 - 3- U) vould ioclude, but zoz neeessarlly b* United to, tha foiloning: e) Tbm Haaletoc Lnbaratorias. b) The Institut* af Industrial Medleine of Hev Tork University. e) Tbe Repartaient of Pharaaeoloey of tha University of Misai Medleal Sebool, unar Dr. UUllaa Deleboann. d) Tha laborntorles of Dr. Pbilllpe Shblk af tfaa Chicago ladlcal Sebool. e) Industrial Bio-Test Laboratories, Incorpomted, unter tha direction of Dr. Joseph Colsadrs ln Chicago. f) Stanford Research Institut*, Dportasnt of BlaLagy, M. T. Valte, M. D., and 0. I. Sessll, Fb.D., diracton. g) USA, Dpartant af Hedleine, Dr. F. Btryan, dlraetor. 5) Tbe daboassdttes on Carclnoganleity raorssianda that tha Medical Adrisory Condttaa approprit* funds 1n tha nount of $50,000 to oover tha oosta of eueh osrelnogsnlo tastlng af axas, at a Labomtory to b* deteralnad at a latar data. In ordar that funda ean ba availabla heginalng Jhly 1, 195 T API 06383 . 1 - 5) fo r auch carclnoganlc ta a tla g , l t la jr opoaad bat th la #90,000 be aat aalte , but not te fln ite lj aar aarVari a t th la tla a , fo r ttaaaa atudlaa. a 8ubeonad.ttea balleraa th a t an aqulvalaot aount o f OOOH7 111 ba naadad aaoh ja a r fo r tte naxt ja a n ln d a r to atudy tha p ro b ls adaqnataly. 6) Tba Stfeoondttaa mnoaante th a t a la tta r alaU ar to tha attaahad ba aaot by tha propar authorlty o f tha API. M H C T Iil sm m sD , Mariaars o f tha Steooaadttaa ob Carnlrmaarrtnlty B. B. tekardt, K. D. - Chadnam B. V. A d 0. B. H a t, N. D. B. K. U n te r, M. D. B. C. MttbofT M. I . Baaqcdat, M. D. A. 0. Pteat CR.haBlz*aBaenl,arSdutb,ooMn.aDlt.ta/aoJohb C aralaaaM ialtr ovaabar 5, 1956 ftttwfiioaiit - Propoaad la tta r to Larogr B. Bonay, taraM B-OaBaral, nsptMdm 13, 1996 API 06384 Uw & M fc tL < * API 06385 * Mobil Socony Mobil Oil C om pan y, 150 E A S T 4 2 N O S T R E E T N E W YORK 17. N Y m, um Inc ! Y . ! t S m 6. I. w u m r!l!! S r !**.* M H III z li, M M u * cnim Mf io API 06386 COPY COPY S o c c n y M o b i l O i l C o m p a n y , Inc. 150 East U2nd Street, New York IT, N. Y. August 20, 1957 Subcommittee on Carcinogenicity Dr. R. Mr. E. Dr. C. E. Eckardt, W. Adams H. Hine ChairmanDr.E. K. Linder Mr. R. C. Mlthoff Dr. M. N. Newquist U. S. PHARMACOPEIA REVISION I have just noticed the following announcement in a recent issue of CHEMICAL AND ENGINEERING NEWS: USP REVISION The revision program leading to publication of the l6tb revision of the U. S. Pharmacopeia has begun. Selection of drugs to be included is going on and the list is well under way. A call will be issued shortly for volunteers to read USP proof. Meanwhile, constructive suggestions for changes in the present USP general tests chapters are invited. They should be addressed to the USP headquarters at k6 Park Avenue, New York l6, New York. It seems like this would be a good opportunity to investigate the possibility of revising USP requirements for paraffin. As you know, present requirements are archaic and do not list tests presently used by the industry for maintaining auality. In our opinion, the specifications could be considerably improved by changing the melting point range, requiring as ASTM color test, and oil content. Also, eliminating the USP acid color test. ACP:lgp cc: E. 0. Mattocks Sincerely yours, /s/ A. C. Fabst A. C. Pabst Industrial Hygienist Medical Department API 06387 SJo * Esso Research and Engineering <F O R M E R L Y S T A N D A R D OIL DE V E L O P M E N T COMPANY) P . O . B o x 4 3. L i n d e n - . N . J . Co m p a n y 1EDICAL RESEARCH DIVISION i O B E R * E E C K A R O T PM O M O D!SCCt O * BERTRAND E BENN'SON M D ASSISTAN" DIRECTOR , ^ --E N D R l C K S C M E -CAD NOUSTRIA,, YGItNIiT -O R A C E W G E R A R O E PM O M D -CAO TOXICQWOQIST October 1 1957 n r. 1. A. Kohoo of Moiltilt Soar Or. Xefcoot . 1. U. Iritiihi1offiooo of tbo IW. If y m twMy tU i Mb Infertonatolgrco net boo ttao la Ckieofo to dlnoMOtldo dth yenprior to ocr i^nrf-e, M&twatti w i l l of tho jjewddoi ttd th*rooeld like to teovjMr M lap tom* ooobi yonotbloIMoro irriogwirt to fdR that in ooirlog their Moo to the >40. Zcold tborefbre graotly ipreeUto It if jobm li lot notero jmr oM iti iQ iH ii tkU. Tory troly yeoro, 1. I. B u m , H. 6. Af is/ejfe tec. - HLaotoo of the Urtinmrlttoo on CardnogoBloi* Bold at tho IlMkstono otol in Chicago Friday, ScptcRbor 27, 1957 (October 1, 1957). (3) act Mr. X. 0. Mottooko ^ 06388 MINUTES OF THE MEETING OF THE SUBCOMMITTEE ON CARCINOGENICITY Held at the Blackstcnc Hotel, Chicago Friday, September 27, 1957 A meeting of the Subcommittee on Carcinogenicity of the Medical Advisory Committee of the American Petroleum Institute was convened in Dr. R. E. Eckardt's suite at the Blackstone Hotel at 9 0 0 a.m. on September 27, 1957. The full. Subcommittee *r.s in attendance, plus Mr. Paul Halley of the Standard Oil Company (Indiana) as a guest. The Subcommittee discussed preliminarily the work at the Kettering Laboratory and wishes to point out that work now being performed by Dr. Horton is far more fundamental in nature than was originally anticipated by the Subcommittee. For this reason the Subcommittee believes that its decision to discontinue sponsoring this research under its direction has been a correct one, and the Subcommittee plans to continue with the recommendation that this work be discontinued as of July 1, 1959. However, the Subcommittee does wish to point out that there are fundamental aspects in the petroleum chemistry now being conducted by Dr. Horton, which might warrant a continuation of this type of research, either at Kettering Laboratory or some other laboratory, under the sponsorship of the Committee for Fundamental Research of the API* The method ology now being pursued by Dr. Horton is primarily chemical in nature rather than biological and might therefore well be considered by the Conmlttee far Fundamental Research. In addition, the Subcommittee discussed in a preliminary fashion, the possibility of suggesting to the MAC that Dr. Kehoe be put on a retainer fee at the conclusion of the work at the Kettering Laboratory on July 1, 1959, in order that Dr. Kehoe might attend all meetings of the MAC and offer us his advice and guidance in some of the problems which the petroleum industry is facing now and might face in the future. It is the Subcommittee's belief that Dr. Drinker's attendance at and participation in the affairs of the MAC have been highly worthwhile and if Dr. Kehoe were willing to accept such a retainer agreement, his participation in the affairs of the MAC would also be worthwhile. At 11 a.m. the group was joined by Dr. R. A. Kehoe, Dr. A. W. Horton and Dr. J. J. Phair of the Kettering Laboratory. Dr. Horton began by presenting a progress report of the work at the Kettering Laboratory during the past five months. He indicated that all the experimental work for the past five months has been in the field of analytical methods. He divided this work into two sections: that work done on carcinogens and that work done on accelerators. Carcinogens To date the work of the Kettering Laboratory suggests that the most significant carcinogens in petroleum oils are polycyclic aromatic compounds, most hydrocarbons. API 06389 He emphasized the difference in concept between the basic carcinogenic potency of an oil, which is that due to the presence of carcinogens vs. the actual carcinogenic potential of the oil, which is the carcinogenic activity resulting from both the presence of carcinogens and of accelerators and inhibitors* He indicated that certain data developed at the Kettering Laboratory have suggested that some sulfur compounds may act as accelerators but that they only do so in the presence of other accelerators* Thus, if there are sulfur-containing accelerators they would not be active as accelerators in the absence of hydro carbon accelerators* Present data at the Kettering Laboratory indicated that the accelerators are probably long-chained hydrocarbons. Suggestive evidence at the Kettering Laboratory indicates that there may be inhibitors present in petroleum oils* These inhibitors do not inhibit the carcinogens, but rather inhibit only the accelerators. This evidence has arisen from some work done by the Kettering Laboratory with two different white mineral oils which were used as diluents of accelerators. It is important to enphasize that these inhibitors are inhibitors of the accelerating action, rather than inhibitors of the basic carcinogenic activity due to the carcinogens* In the past five months almost all of the work done by the Kettering Laboratory on carcinogens has April 1957 report, been as 3 ld/o2n-erionngwhaartomatthiecys.havTehepsreevicoonussilsytidoefnptyirfeineeds,in the fluoranthrenes, cyclopentanophenanthrenes, and benzfluorenes* Dr. Horton believes that these 3 l/2-ring aromatics are probably the most important class of car cinogens in most petroleum oils* The work has been done principally on API-8 and fractions of API-8, as diagramatically indicated In the attached diagram* Descriptivly, API-8 was subjected to a theoretical 80 plate distillation* Examination of the 660*F fraction suggested that only 0.001$ of carcinogens was present in this fraction but that it contained a very high concentration of accelerators. This evidence is supported in part by the fact that tumors appear rapidly but only at a very low total incidence of tumors* Following the work on this fraction, Dr. Horton next concentrated his attention on three fractions which boiled in the range of 730*F to 760*?* These fractions contain very little accelerators* These three fractions were subjected to maleic anhydride treatment in order to remove the anthracenes and their derivatives* Testing suggested that *03 out of *21 of the carcinogens present in this fraction was due to carcinogens of this type. Roughly, therefore, 1/7 of the basic carcinogenic activity of these three fractions is due to anthracenes and their derivatives* The raffinate from the maleic anhydride treatment of these three fractions was next combined and chromatographed, and two fractions were obtained, one of which contained the benzfluorenes and experimental work has suggested API 06390 3 that these are unimportant in the total carcinogenicity of these three fractions. The other fraction contains the remaining three classes of carcinogens, namely, pyrenes (and their methyl and dimethyl derivatives) cyclopentanophenanU'renes, and fluorairthrenes(principally the dimethyl derivatives). At the present time, Dr. Horton is working on the separation of these three types of aromatic hydrocarbons in the raffinate from the maleic anhydride treatment of the 730*F to ?60"F cuts of API-8, This is being done by liquid-liquid partition between 99% sulfuric acid and iso-octane at -30*F. Dr. Horton says that this treatment will separate the pyrenes from the other two classes of compounds. The raffini.te of this extraction then is chromato graphed and treated with picric acid which may lead to the separation of the cyclopentanophenanthrenes from the fluoranthrenes. Dr. Horton did indicate that of seven oils carried through the maleic anhydride extraction step, only one was found to have much benzanthracene which contributed to carcinogenic activity. This one oil was from a coker gas oil (API-33) in which 7/ U of the basic carcinogenicity was due to benzanthracene-type compounds, This contrasted with other types of oils in which only 1/7 of the basic carcinogenicity is due to this type of compound. In work which Dr. Horton did with a thermally cracked, cat cracked, oil he found that the benzpyrene and it-ring carcinogens almost doubled in concentration* but the activity of the oil decreased. This result might be due to the destruction of accelerators or to the destruction of the 3 l/2-ring carcinogens. It is Dr. Horton's belief that possibly this reduction in activity is most likely due t3o1/th2e-rdiensgtrcuacrtciionnogeonfs.the accelerators rather than to the destruction of the Accelerators At the present time, Dr. Horton is following dues which have been provided for the presence of inhibition of accelerators in petroleum oils. He believes that these inhibitors probably fall into a class of compounds referred to as polycydoparaffins. These have essentially the same structure as the aromatlo carcinogens except that they are saturated compounds. In partial support of this, Dr. Horton pointed out that Zechmelster and Kotin reported about a year ago in SCIENCE, that hydrogenated aromatics inhibit sarcoma production when injected subcutaneously. However, they used ettyl laurate as a solvent for their carcinogens and ettyl laurate would be expected to be a highly accelerating solvent. Therefore it was not dear from their work whether they were inhibiting carcinogens or inhibiting accelerators. It is Dr. Horton's belief that the inhibition they observed is most likely the inhibition of the ethyl laurate as an accelerator rather than true inhibition of the carcinogens. ApI 06391 - u- In discussing the so-called preconditioning of an animal by accelerators, it is Dr. Horton's belief that this occurs through an accelerator "setting up" the animal for other accelerators. In other words, preconditioning does not precondition the animal for carcinogenic activity but only for accelerating activity. Support for this belief is contained in the fact that if the animal is painted with an oil essentially free of accelerators following preconditioning it is not possible to demonstrate the preconditioning effects, but if an oil high in accelerators is used after the preconditioning treatement, the preconditioning effect can be demonstrated. The white oils being studied by Dr. Horton for so-called inhibiting effects (principally API-80; are free of nparaffins. They contain some isoparaffins and condensed cycloalkanes which represent the greatest amount of material present. The suggestion at the moment, therefore, is that these condensed cycloalkanes are inhibitors of accelerators. In an attenpt to separate these inhibitors from other compounds present in the white oils, Dr. Horton is going to use distillation, thiourea separation, and liquid thermal diffusion. In addition, he may possibly consider the use of molecular sieves. Dr. Horton submitted his Interim Report on his work dated September 26, 1907 which was distributed to the Subconmittee at this meeting. Epidemiology Next, Dr. J. J. Phair gave a progress report on the epidemiological work. Dr. Phair indicated that he had conpleted the coding and punching of the cases. In this process he felt it necessary to discard some cases since the informatior contained on the report was inadequate. Hence, the total number of cases reported in his final report will not be the same as in previous reports from Dr. Phair. At the moment, the status of this final report is that the intro duction, the objectives, and so forth have already been written up and the data tables are now being prepared and the comparisons and correlations will be made. It is hoped by both Dr. Phair and Dr. Kehoe that this final report can be made available to the Subcomsittee by the first of the year. In Dr. Phair* s work he pointed out that in the cases occurring after 1950, 28% of the tumors have been found to be skin tumors, whereas, only 15.3% of the cases prior to 1950 were skin tumors. In general population figures available, 16.6% tumors are skin tumors. Vihether this increase in the relative number of 8kin tumors in the post-1950 group of cases is significant, is not now known. Dr. Phair is at present making age, geographic location, primary site and occ upational-group breakdowns of the cases which he analyzed. API 06392 - 5- Following Dr. Phair*s presentation, the Subcommittee discussed in private with Dr. Kehoe certain phases of the relationships between the Subconrndttee and the Kettering Laboratory and it was concluded that these relationships remain on a friendly, amiable, and professional level. The Subcommittee meeting broke up at approximately It p.m. on September 27, 1957, without having set a date for its next meeting. R. E. ECKARDI, H. D./cjh Chairman, Subcomittee on Carcinogenicity October 1, 1957 AttachMBt API 06393 API-6 80 Plate Distillation 660 v fraction -- .001/6 carcinogen. Much accelerators Tumors appear rapidly but at low incidence S' 730-760 (3 fractions) little accelerators Maleic Anhydride of the 3 cuts------ > anthracenes and their derivatives - .03 out of .21, i.e., 1/7 v Raffinate iChromatographed------ > bensfluorenes (unimportant) N< Pyrenes - methyl St dimethyl Cyclopentanophenanthrenes Fluoranthrenes - dimethyl derivatives Now working on separation of these 3 hydrocarbons I Liquid-liquid Piasrot-iotcitoannebeattwe-e3n0*99s%epsaurlaftuersipcyraecniedsanfdrom other 2 Raffinate Chromatography it picric add API 06394 MINUTES OF THE MEETING OF THf,(amcnMMTTTF^ ON CARCINOCDJICITY Held in the Conrad Hilton Hotel in Chicago"" Wednesday, November 13, 1957 The Subcommittee on Carcinogenicity held a meeting at the Conrad Hilton Hotel in Chicago at 9 a.m. on Wednesday, November 13, 1957. The following members were in attendance: E. W. Adams C. H. Hine, M. D. E. K. Linder, M. D. M. N. Newquist, M. D. A. C. Pabst R. E. Eckardt, M. D. - Chairman In addition, the following individuals attended the meeting as guests: R. D. Bent Lamson Blaney, M. D. L. F. Boys, M. D. C, T. Brown R. C. Cole L. E. Curtis, M. D. T. M. Frank, M. D. H. W. Gerarde, M. D. N. J. Gothard J. H. Hege, M. D. R. M. Landon B. B. Reeve, M. D. F. J. Sanders L. J. Wade, M. D. The purpose of the meeting was to discuss the report of the Subcommittee to the MAC that afternoon. In addition to the three points mentioned in the Chairman's letter to the Subccssdttee, it was decided to add a fourth point} namely, that the Subcommittee solicit comments and criticisms from all members and advisors of the MAC about the outline of the final report of the work at Kettering Laboratory which was attached to Dr. Horton's Interim Report dated September 26, 1957* The Chairman of the Subcommittee then summarised for those in attendance the present status of the wax situation. Briefly, the situation is that a Mr. Kellogg of the Milk Industry Foundation in Washington had collected kD wax samples from dairies which he had forwarded to Dr. Hueper. Twenty-four of these were forwarded to Dr. Sfaubik and UV absorption data on these 2k samples obtained by Dr. Shubik's chemist indicated that the UV absorption at 290 millimicrons varied from 0.0U to infinity. From one sample, in which the total absorption at 290 had been greater than 3*0, he chromatographed and isolated U micrograms of 1,2,5,6-dibensanthracene API 06395 - 2 - per gram of wax. It was the considered opinion of Dr. Shubik that he believed this quantity of the known carcinogen, 1 ,2,5f6-dibenzanthracene, in milk carton wax is undesirable and that the petroleum industry should establish an immediate standard which does not permit this much carcinogen in the finished product. Long range work then would attempt to establish a standard based upon biological testing. In discussions which the Chairman had with Dr. Hueper at the recent Lung Cancer Workshop at the American Cancer Society, Dr. Hueper indicated that he was willing to sit still as long as the industry was willing to approach this problem with a reasonable, rational attitude, and as long as he was kept informed of the results of any work which was done. The Chairman indicated to the Subcommittee that the Three-Man Wax Committee appointed by the Medical and Health Committee of the Board, had met in Chicago on October 2U and unanimously recommended to the Medical and Health Committee, that work be done on waxes to the extent of approximately $100,000 a year for the next three to five years in Dr. Shubik* s laboratory. Copies of the report of the Three-Man Wax Committee will be made available to the members of the MAC through Mr. E. 0. Mattocks1 office of the API. The meeting was adjourned at approximately 10t30 a.m. R. E. ECKARDT, M. D./cjh Chairman, Subcommittee on Carcinogenicity November 1U> 1957 API 06396