Document byG0E35rOy0xmQpEngEzj5m21

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1955 Oct 1 DOC#: API129 DOCUMENT DESCRIPTION: API Research Project MC-1 - Tabular Summary of Current and Completed Biological Experiments - The Kettering Lab TABULAR SUMMARY ' OP CURRENT AND COMPLETED BIOLOGICAL EXPERIMENTS October 1, 195$ Department The Kettering Laboratoryin the of Preventive Medicine and Industrial Health College of Medicine University of Cincinnati Cincinnati, Ohio API 06476 TA3LES labi I - Carcinogenic Potency of Various Fractions from the Refining of Petroleum Table II - Control Experiments with Various Solvents Table III - Experiments Involving the Application of Solutions of Methylcholanthrene in Various Solvents Upon the Skin of C3H Mice Table IV - Experiments Involving the Application of Solutions of 3enzopyrene in Non-accelerating Solvents to the Skin of C3H Mice Table V - Experiments to Determine the Potency of Mixtures of Polycyclic Hydrocarbons in Technical White Oil for the Skin of C3H Mice Table VI - Experiments Involving the Application of Solutions of Methylcholanthrene in Dodecylbenzene Upon the Skin of Mice Table VII - Accelerating Activity of Various Solvents on Rate of Induction of Tumors by Dissolved Benzopyrene (BP) in C3H Mice Table VIII- Effect of Early Exposure to Accelerating Solvents on Results of Subsequent Exposure to Carcinogen Table II - Experiments to Determine the Carcinogenic Promoting Activity of Various Materials for the Skin of C3H Mice . ( Table X - Effect of Termination of Exposure of C3H Mice to Catalytically Cracked Oils at a Critical Phase of the Experiment Table XI - Experiments to Determine the Potency of Certain Polycyclic Hydrocarbons for the Skin of C3H Mice Table XII - Experiments on the Retardation of Tumor Formation by Washing PI 06477 INDEX TO PPCCESSES Process___ _ ^on_catalytic cracking of virgingas oil Non-catalytic cracking ofcatalytic gasoil Steam cracking Viscosity breaking pubbs coking gatch coking Delayed coking Naphtha reforming polyforming Hydroforming Thermofor catalytic cracking (T.C.C.) Fluid catalytic cracking (F.C.C.) Houdry Cycloversion Solvent extraction Straight run distillation Fractional distillation Lubricating oil Wax pressing Filtration dewaxing Desulfurization by catalytic hydrogenation Acid treating Viscosity effects Fuel oil blending Diels-Alder reaction Air oxidation Solvent extraction with concentrated HgS04 Fractionation of API-12 Chromatography Table I ya5 Number 1 1 3 3 3 3 3 [. 1; 6 3 3 9 9 10,13 11 11 11 11 12 12 12 13,15,16 II4. 16 16 17 -'* .- -'c* v INDEX TO TABLE I Process ? D 7 9 3-3 3-1+ 3-5 5-6 - 12 8-l2a 3-13 6-13& - i 9-11+ - 15 6-16 8-17 3-18 8-19 3-20 8-21 8-22 9-23a - h 3-21+ 3-2 5 a 8-25b 8-26a - d 8-26e - n fl-26n-l 3-26-2 8-26-3 9 10 11 12 12-2 12-7 12-8 13 lb 17 18 19 20 20-1 21 22 27 23-1 23-2 21+ 25 25-1 26 27 23 29 'ion-catalytic cracking of virgin gas oil Non-catalytic cracking of virgin gas oil T. C. C. P. C. C. Filtration dewaxing Dilution of API-8 Chromatograpny Fractional distillation Diels-Alder reaction Fractional distillation Chromatography Fractional distillation Dilution of API-8 Chromatography Fractional distillation Solvent extraction with Solvent extraction with Dilution of API-8 Chromatography of API-8 of API-8 of API-8 of API-8 cone. HaS04 cone. HaS04 Diels-Alder reaction Chromatography Diels-Alder reaction Diels-Alder reaction Fractional distillation Fractional distillation Diels-Alder reaction Chromatography Chromt ography To Co Co To C Co Koudry F. C. C. Chromatography Fractionation Fractionation Polyforming v Solvent extraction Solvent extraction Viscosity Naphtha reforming Non-catalytic cracking of catalytic gas oil Dilution of API-20 Desulfurization by catalytic hydrogenation Cycloversion F. C. C. Solvent extraction with cone. HaS04 Solvent extraction with cone. HaS04 Non-catalytic cracking of catalytic gas oil Distillation Dilution of API-25 F. C. C. Solvent extraction Delayed coking Catalytic feed to non-catalytic cracking Tac le page Number 1 1 5 6 11 6 6 13 13 13 17 13 b 6 13 16 16 6 + 15 . 6 15 15 13 11+ 15 11+ 11+ 5 5 8 7 7 16 16 1+ 9 9 3 1+ 1 1 20 8 1,7 16 16 1 7 7 7 9 3 1 API 06479 5c i?le 'lumber 3 31 32 33 3*+ 35 36 37 38 39 1*0 1*1 1*2 1+3 1+3-1 i+l+ i+5 1+6 1+7 1+8 1+9 50 51 52 53 51+ 55 56 57 58 59 60 61 62 63 61+ 65 66 67 68 69 70 71 71-1 71-2 72 73 7i+ 75 76 77 78 79 81 INDEX TC TAPIS I Process Non-catalytic cracking of catalytic gas T. C. C. Wax pressing Delayed coking Houdry Non-catalytic cracking of catalytic gas T. C. C. Polyforming Catalytic feed to non-icatalytic cracking Non-catalytic cracking of catalytic gas T. C. C. Delayed coking Fa Ce C a Fa C a C Dewaxing F. C. C. Non-catalytic cracking of catalytic gas i F. C. C. Non-catalytic cracking of catalytic gas 1 F. C. C. Hydroforming Houdry Houdry Dubbs coking Dubbs coking Catalytic feed to non-catalytic cracking Non-catalytic cracking of catalytic gas Straight run distillation Wax pressing Naphtha reforming Non-catalytic cracking of virgin gas oil T. C. C. Non-catalytic cracking of catalytic gas Acid treating Houdry Non-catalytic cracking of catalytic gas 1 Non-catalytic cracking of virgin gas oil Viscosity breaking Viscosity breaking Fa C a C a Polyforming Solvent extraction T. C. C. Chromatography Chromatography Non-catalytic cracking of virgin gas oil Fa C a C Delayed coking Solvent extraction Naphtha reforming Hydroforming T. C. C. Straight run distillation Houdry Table I Page Number 1 5 11 3 1,8 1 5 k22 5 k 7 7 7 2.7 2 22.7 1 \ 8 3 2 3 2 9,11 11 k 1 25 12 2.8 2 1 3 3 7 9 5 17 17 1 7 3 9 i+ k 5 98 API 06480 I . .noie mb er 82 63 n 8^-1 S3-2 81+ 8 86 87 88 89 8999--1 2 89-3 90 91 92 93 9b 96 9978 99 100 100- 1 100-2 101 102 103 10I+ 10? 108 109 110- 1 111- I+ 111-l+a 111-l+b 111-5 111-6 111- 7 112- 1 112-3 113 111+ 111+-1 115 117 118 119 120 120-1 INDEX TO TABLE I _________________ tr o c o a a T. C. C. Air oxidation Air oxidation Chromatography- Delayed coking F C C Steam cracking Batch coking F. C. C. F C C Diels-Alder reaction Diels-Alder reaction Chromatography Delayed coking Catalytic feed to non-catalytic cracking Non-catalytic cracking of catalytic gas oil Non-catalytic cracking of catalytic gas oil Non-catalytic cracking of virgin gas oil Delayed coking Delayed coking Delayed coking Lubricating oil Lubricating oil Lubricating oil Lubricating oil F. C. C. F. C. C. Delayed coking F. C. C. Straight run distillation Non-catalytic cracking of virgin gas oil T. C. C. Fractional distillation Fractional distillation Fractional distillation --' ' Fractional distillation Fractional distillation Dilution of API-111-1+ ' Dilution of API-111-1+ Fractional distillation Fractional distillation Fuel Oil blending Straight run distillation Viscosity effects Straight run distillation Straight run distillation Fuel oil blending Fuel oil blending Straight run distillation - Diels-Alder reaction Table I Page Number 5 .11+ 11+ 11+ 3 7 3 3 7 7 16 16 7 3 2,8 2 2 1 13 + 1+ 11 11 11 11 8 8 6 9 1 5 10 10 10 10 10 10 10 10 10 12 9,12 12 10 10 12 12 9 16 API 06481 IMOGENI7 F!TENCY OP VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM API HUMBER DESCRIPTION OF EXPERIMENT 1RAVITY API] FRACTION DISTIL LING <750F. {%) SCHEDULE OF APPLICA BENZO TIONS PYRENE ]no./week {%) - mg.) RELATIVE INCIDENCI CARCINO OF GENIC TUMORS POTENCY, % - week] PMC on-cat,alytic cracking nf VIJgin gas oil 2 Cracked Side 21.2 stream 0.0002 1 - 100 0-75 - 6 Cracked residuum 5.2 33 0.013 3 - 100 72-30 rw 0.08 59 Cracked residuum 8.5 0.005 3 - 100 82-69 0.02X 65 Cracked residuum 6.6 1+3.8 0 .01+ 3 - 100 89-29 0.11X 72 Cracked residuum 9.6 35 0.06 3 - 100 73-18 0.21X 91+ Cracked residuum 10.1+ 35 0.02 3 - 100 80-39 0.09X 108 Cracked residuum 2.3 32 0.12 3 - 100 71-28 0.12X 108 3 - 5 100-52 o .o 5 .o i Non-catsalytic cracking of cal;alytic gas oil 20 20 20-1 Cracked residuum 1+.7 50% oil No. 20, 50% dodecylberzen 9 23 FCC gas oil feed 26.7 23 21+ Cracked residuum 5.9 from No. 23 29 TCC gas oil feed 15.7 30 Cracked residuum 8.5 from No. 29 31+ Houdry gas oil 28.0 feed 35 Cracked residuun 2.7 from No. 3l+ 51 78.5 32.3 73 36 35 0 .21+ 3 - 100 3 - 100 3 - 100 100-22 90-21 100-25 ryj 0.18 0.17X rJ 0.18 0 .01+3 0 .21+ 3 - 100 2 - 100 3 - 100 100-19 91+-28 100-15 AJ 0.21+ 0 .22!;^ nJ 0.1+ 0.10 0.23 0.011+ 1 - 100 1 - 100 81+-30 100-33 3 - 100 81+-32 0 .3l.Oi+ - 26-.' 02 1 <0 o . l 0.18 3 - 100 100-20 A) 0.15 API 06482 TABLE I e.) 'ccsEr:: f :t e n c y of v a r i o u s f r a c t i o n s f r o m t h e r e f i n i n g o f p e t r o l e u m '-a _ ' ' " -- 1 ..... ----1- .... ' ----------- ____ API SAlffg ffirMBFR_ DESCRIPTION OF EXPERIMENT Total cracking 3S charge; combin ation unit 1RAVITY PAPl! FRACTION DISTIL LING <75f . (JO SCHEDULE OF APPLICA BENZO TIONS PYRENE [no./week (JO - mg.) RELATIVE INCIDENCII CARCINO OF GENIC TUMORS POTENCY, - weeki ?MC L6.1 32.2 J10.005 3 - 100 62-58 aJ 0.06 Cracked residuum) 7.8 from No. 38 31.0 0.03 3 - 100 56-21+ /'Z 0.15 FCC decanted oil]l5.2 feed 31.1 0.15 1 - 100 91+-1+0 0.22X Cracked residuunj-1.7 from No. 1+1+ 26.1+ 0.38 1 - 100 88-1+1 0.18X FCC gas oil feed 87.9 0.03 3 - 100 100-21+ ^ 0 . 1 5 Cracked residuum from No. 1+6 76 0.21 3 - 100 93-17 rJ 0.22 Total cracking charge 93.9 0.01+1 3 - 100 IOO-36 r J 0.09 Cracked residuum from No. 55.9 0.23 3 - 100 89-19 ro 0.21 Cracked residuum Houdry gas oil feed 66.8 1+8.5 0.05 0.05 3 - 100 3 - 100 3 - 100 3 - 100 2 - 100 3-20 3 -5 88-26 89-26 100-19 89-28 100-33 100-1+5 86-37 f j 0.20 O0 -1TP2*- .0^12 0.184.03 0.21X .3.51:82 0.11!o3 o.0 9 !;8 | 61+ from No. 63 52.5 0.11 3 - 100 100-23 0 .1 7-.0 2 FCC gas oil fe< 80.1 0.037 2 - 100 95-23 Cracked residua from No. 91 70.5 0.072 2 - 100 91-23 o.3i!;8| 93 Cracked residuumj 7*9 87 0.03 3 - 1 0 0 91+-1+0 0 .07-.01; API 06483 AaJ3 -- i V.'S"]"'"~ PnOnTENCY OP VARIOUS FRACTIONS FROM TRR REPINING O? PETROLEUM API 06484 TA3LE I (page 5) :n c g e n i c p o t e n c y c f v a r i o u s f r a c t i o n s f r o m the r e f i n i n g cf p e t r o l e u m API sample jjMBER DESCRIPTION OF EXPERIMENT SCHEDULE FRACTION OF DISTIL 1APPLICA- INCIDENCE GRAV( LING BENZO TIONS OF ITY 750F. PYRENE (no./week TUMORS APX (%) (*) - mg.) (#-weeks) RELATIVE CARCINO GENIC POTENCY, MC jhermofor Catalytic tracking 'racked residuum 20.2 a ; lo o 9 Cracked residuum I8.i| 97 9 10 bracked residuum 11.6 56.7 10 31 bracked residuum 1 6 .0 63 36 Cracked residuum 21.9 N 50 UO Cracked residuum 19.8! 77.2 t 71 Cracked residuum 22.a 77 71 71 7U 71 71 78 Cracked residuum 16.1 45.7 82 Cracked residuum 13.6 25.7 82 0.019 0.07 0.23 0.65 0.18 0.09 0.10 o .4 r 0.53 1 - 100 3 100 3 100 1 100 1 100 1 100 1 100 1 - 100 l 100 1 20 2 20l 2 201 25 15 1 100 1 100 1 10 11-56 100-47 100-41 o .o 5 .o i /V 0.06 94-39 90-31 100-32 94-44 100-42 0 .3X a ^o .5 u,J'-.09 0 `i1Q9-+.*o^5 0 .16X 90-22 0.52I .05 90-37 -36;g| 100-27 100-25 0.2.02 U0 'd2l1+-.*Q^2 94- 36 O.I9+ .05 .03 85-70 O.lOi.03 88-20 *60-.* 95- 34 o .3o !;8 100-50 o .2o !;i 60 Sidestream 109 Sidestream ;249 100 24*1 <.0004 3 - 100 0.35 3 - 100 57-48 93-25 r J 0.031 0.14.03 API-71 involved repeated application until death. API-71A involved repeated application only until appearance of papilloma in each mouse. No significant difference in the average time to the appearance of gross carcinoma was noted. ______ __ ______ API 06486 TABLE I (page c) ^ RCliiOC'ENIC POTENCY OP VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM sample DESCRIPTION OF EXPERIMENT FRACTION DISTIL GRAV LING ITY <750F. ;a p i ' (%) SCHEDULE OF IAPPLICA- INCIDENCE BENZO TIONS OF PYRENE (no./week TUMORS {%) - ag.) ({6-weeks ) RELATIVE CARCINO GENIC POTENCY, PMC pMd Catalytic Cracking Cracked residuum 11.:. 75 0 .1+2 i -i8-:26 - -\U y 0.6 0.2X 0.1+01.03 i-fiL -57-:i3 91-1+0 100-32 884+8 100-18 O.ZlUos 0.23.05 o.37t;^ 0.20!;OJ .25:;g| 8-1+ 8-16 8-21 $ 0 % API-8, 50^ (white oil + W. Texas residuum) - 50# API-8, sec .-amylbenzene 50% API-8, $ 0 % API-8-21+ Chromatography of API-8 : Aromatics 8-21+ Colorless fraction 257 8-17 Solution of 0.239)6 BP in API-8-21+ Reblend of all fractions 3 - 100 1 - 100 1 - 100 1 - 100 1-100 3-50 1 - 100 90-23 100-52 87-i+3 79-28 92-22 0-86 100-1+3 91+-30 O.ll+X 0n.118ft"_*"*n0c1r rJ 0.3 0.1+2X 0 .1 5 ^ .0 2 OD OD 11 VA VA H 1 v0n i - v - a~= . / VARIOUS FRACTIONS FROM THE RZFININ:- OF 'i t r c l i y m ij J 1 API sjaMPLE I \njf4BER 12 12 12-2 DESCRIPTION CRAV- OF ITY EXPERIMENT ;api Cracked residuum 18.1 Colorless fraction from chromatography FRACTION DISTILLING <75o f . M) 5 700+ bottoms frcr+24.3 49 cracked residuum 5ENZ0PYRENE [%) O.42 0.09 SCHEDULE OF APPLICATI0NS |no./week - mg. ) 1 - 100 3 - 100 3 - lOCf 3 - 100 INCIDENCE OF TUMORS iC-weeks ) 88-34 100-14 0-93 95-19 RELATIVE CARCINO- GENIC POTENCY, Fvip a '0.4 A/0 .4 - 0.24i.03 25.1 ZOfc API-25, 50# 21.1 (White oil + Vfest Texas residuum 3 - 100 92-4O r\ ' r- f O.UV- ,0021 2b Tracked residuum 7.3 0I .3 0.63 1 - 100 100-20 O.oX 42 Cracked residuum 14.2 28.6 0.36 1 - 100 94-34 43 Cracked residuum 24.; 24.5 0.27 1 - 100 100-37 0#l8-.02 43-1 Dewaxed API-43 12. C 29.5 1--1 1 1+3-U (1+4) Cracked residuum 15.2 1+3 Cracked residuum 6.C 08 Cracked residuum 9.8 73 Cracked residuum 17.8 73 31.1 47.1 43.3 21 0.47 1 - 100 2 - 201 2 - 201 0.15 1 - 100 0.32 1 - 100 0.52 1 - 100 0.35..: 1 -,.100 1 - 100 95-25 94-17 100-19 94-40 100-36 100-17 83-22 100-31 0.37*.04 0.36i;gI -32i;8| 0.22X 0.19X 0.59!;^ 0 .41X o .27 *.85 35 Cracked residuum 8.1 42.6 0.42 1 - 100 100-25 .u4;g| 23 Sidestream 23 46 Sidestream 26.7 78.5 23.8 87.9 0.027 0.033 3 - 100 2 - 100 3 - 100 100-19 94-28 100-24 ^0.24 o-22-!o^ AVO.15 88 Sidestream 22.5 69.3 0.029 2 - 100 94-26 o.25;g| 89 jSide stream 2 7 .c 100 0.001 3 - 100 89-21 0.26! ; ^ 39-3 }+-rineed ^ornati cs of API-89, jLl.0% solution in benzene 3-20 0-1 - API-i+3~l involved repeated application until death. API-43-1A in volved repeated application only until appearance of papilloma In each mouse. No significant difference in the average time to the appearance of gross carcinoma was noted. Painting discontinued after I4.I weeks._____________ API 06488 IC a i , TA. texcy cf various fractions from th: FINING CF PETROLEUM API sample ^JMBER DESCRIPTION CF EXPERIMENT r"~ 91 ic: Sidestream Sidestream 1 102 ; 102 Sidestream 101+ 1i 101+ 1 j"oudry Sidestream FRACTION DISTIL- JRAV- LING ITY <750F. "API) (*) SCHEDULE OF APPLICA- BENZ0- TIONS PYRENE `no./week (%) - mg.) RELATIVE INCIDENCE CARCINC- OF GENIC TUMORS POTENCY, (-weeks) PMC 20 J+ 80.1 0.037 2 - 100 95-23 0.26!;" 21+o8 89.7 0,007 3 - 100 100-121 0.33X 23 o5 99 0.015 2 - 2 0 2 - 100 69-U-3 1 93-321 0,1 :X 0.16X 25.8 0,011 2 - 2 0 75-531 . 0.03X 2 - 100 89-2c1 0 0iO aU* II Cracked residuum if.3 81+ 0.21 3 - 100 9h-l9 0 .19X 31+ Cracked residuum 23.0 90 0.011+ 3 - 100 84-32 Ay 0,1 So Cracked residuum 21o3 85 0.07 3 - 1 0 0 100-21 aj 0,2 51 Cracked residuum 25.7 83 0,06 3 - 100 83-19 a/ 0.2 63 Cracked residuum 25.6 i+8.5 0.05 3 - 100 89-26 ,, ,> .0 2 0 1 2 - ,0 1 63 3 - 100 100-19 0.l9i.03 63 3 - 100 90-26 0.21X 3 2 - 100 100-33 ,15-l| 63 3 - 2 0 100-1+5 o . u i . 0 3 63 3 -5 88-37 31 Cracked residuum 22.7 1+0.8 81 91 lycloversion 22 Cracked residuum 25.6 i+9.5 0.20 1 - 100 100-36 1 - 100 91-I+I 1-20 97-52 0.091 3 - 100 100-17 o.20;g^ o .2 ix 0 . 11+x 1 i !1 a/0,3X | l 1 ! The pattern of response to the irritational effects of this oil was similar to that observed with dodecylbenzene. API 06489 TABLE I (?a?e C) potency cf various fractions from the refininc- of petroleum API gAMPLE tjUJER description of EXPERIMENT FRACTION DISTIL GRAV LING ITY <750F. V I ) (*) SCHEDULE OF APPLICA INCIDENCE BENZO TIONS OF PYRENE 1no./week TUMORS {%) - mg.) [%-weeks) RELATIVE CARCINO GENIC POTENCY, PMC solvent extraction lb Phenol extract 9.7 from Coastal 16 900-X Duosol extract 7.1 3 V from California waxy residuum, 5Of? in sec.-amyl benzene Phenol extract 11.0 80 from San Joaquin naphthenic dis tillate 70 Nitro-benzene ex15.7 5 tract from Barbers Hill 60/80 75 S0a extract from +.1+ 100 TCC gas oil .003 ^.006 3 - 100 3 - 100 3 - 100 67-73 i+3-70 87-62 /V 0.01 ny 0.01 s-J o.ix S .002 3 - 100 89-17 ^ 0.3 0.007 3 - 100 93-1+1+ 0.06.01 .001 3 - 100 77-51 /\j 0.05 Straight; run distillatici r 5b Waxy Midcontin 29.9 ent distillate 5b 5b 1 79 San Joaquin naphj-16.6 thenic lube dls-j tillate, narrow cut 52.1+ r j 13 0.003 . 3 - 100 3 - 100 3-20 88-22 65-1+2 81+-51+ /v 0.16 0.09X 0 .06X <.005 2 - 100 86-57 ( 1 ! O.lOX ' 120 Ditto, wider cutil9.5 r J $ 2 X ?.003 3 - 5 0 1 65-60 o.o7+- ; ^ 105 iWest Texas par 28.9, 72.9 '0.0003 3 - 100 !affin distillate i 1 , i 88-33" 1 0.ill*03 111+ Gulf Coastal ;distillate 111+ I21+.61 rv 501 i1 ! 4 .002! 3 - 2 0 51+-83 ; 0.Ol.01 1 3 - 100 ! 55-71 0.02X 1 A.S.T.M. distillation. a The pattern of response to the irrltational effects of this oil was m similar to that observed with dodecylbenzene. API 06490 " --- API sample DUMBER DESCRIPTION OF EXPERIMENT ;s t r a c t i o n s ef.c m t :e r e f i n i n : PETROLEUM , FRACTION DISTIL- GRAY LING ITY <750F. a p i : ($) SCHEDULE OF APPLICA INCIDENCE BENZO TIONS OF . PYRENE (no,/week TUMORS ($) - mg.) \% -weeks) RELATIVE CARCINO GENIC POTENCY, PMC ii5 Blend of Gulf 23.2 50 ` Coastal distil U 5 lates 117 Gulf Coastal distillate 30.s r j 90 1 .002 3 - 20 3-50 0.000 3 - 50 77-80 63-66 75-04 0.02X - pr a c t i c >nal distillation ( S r i t i s h Medical Re sear *ch Council) 110-1 Kuwait Naphtha 61.0 100 l l l - k Lagunillas dis 23.0 tillate 111-1+ 111--i+a 75$ API-lll-U, 25$ benzene 22.7 lll-l+b Lagunillas dis tillate b. 650 690 1 Solution of .16$ BP in API-lll-i+b in-5 75$ Lagunillas residuum, 25$ benzene I5.il 111-6 50$ API-110-1, 50$ API-lll-U 111-7 50$ API-111-1+ 50$ API-112-1 112-1 Oklahoma naphtha 65.9 100 112-3 Oklahoma ' 39.7 distillate 3-20 3-20 3 -5 3 -5 2 - 15 0-55 88-22 614.-75 51-82 - ' o.o4;^ 0U.oU?B+_a002i 0-1+7 3 - 50 100-16 u0.t3Ob_o017- 3'- 5 3-20 56-71+ 0.02.01 . 77-31 i 0.09 .01 ; 3-20 76-104 3-20 3-20 0-50 - o-56a 3 a A.S.T.M. distillation. 8 Two papillomas appeared at 20 weeks but regressed. The pattern of response to the irritations! effects of this oil was similar to that observed with dodecylbenzene. API 06491 TA-LE I (page . .. -ycGENIC p o t e n c y c p v a r i o u s f r a c t i o n s f r o m t h e r e f i n i n g c f p e t r o l e u m API sample DUMBER DESCRIPTION CP EXPERIMENT RAV ITY API FRACTION DISTIL LING <750F. (*) SCHEDULE OF RELATIVE APPLICA [NCIDENCE CARCINO BENZO TIONS OF GENIC PYRENE [no./week TUMORS POTENCY, (*) - "g.) [% - weekj* PMC y.nbrieating oil 99 Naphthenic dis- 20.0 ^v/38 tillate contain ing antioxidant 100 Solvent extract-29.5 rJ 0 ed, no additives 100-1 0.2^ Antioxidant1 in API-100 <.001 3 - 100 94-47 0.061.01 <.001 3 - 100 0-80 - 3 - 100 O-78 - 100-2 0.5* Antioxidant, 2,6-ditert.-butyl4-methylphenol in API-100 3 - 100 0-88 ; fax pressing 32 Dewaxed paraffin distillate frac tion from Lima crude 0.000 (3-6)-100 50-32 - 100-40 56 Feed to^presses 29.9 52.4 0.003 6 - 100 50-15 - 87-22 57 Dewaxed oil from API-56 28.7 80 .002 .6 - 100 50-17 100-25 Filtration dewaxing of JLPI-8 3-3 Filtrate oil, 11.3 65 85* of original (.94* S) 3 - 100 90-17 n+.06 *30_.o 4 !Desulfurization of 8-3 by catalytic hydrogen ation Hydrogenated heavy gas oil M 5 * S) J Same type additive Three applications thereafter. 18.1 74 O .23 3 - 100 100-13 as that contained in API-99. per week for 14 weeks, six applications 1 n -/+.07 *36_.oi+ i per week API 06492 M 3 LE I (page ~~) 'pjtCTBOG10 PCTENCY 0P VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM A?1 js^lpBSER DESCRIPTION OF EXPERIMENT GRAV ITY i"API FRACTION DISTIL LING <750F. (JO BENZO PYRENE (JO SCHEDULE OF APPLICA-tNCIDENCE TIONS OF no./week TUMORS - mg.) 56-weeks) RELATIVE CARCINO GENIC POTENCY, MC Hydrolyzed acid 14.2 sludge effect of viscosity on ^ - induction_______ Gulf Coastal distillate. 35 Sbo/xOO 21*.6 N 50 95Ji A P I-Ill*, $i l25.il alkylpolystyrene 17b U/Iuu - jvusl oil Blending 113 Industrial fuel 6.3 1*3 oil 118 Catalytically cracked residuum component of API-119 35.2 10* a p i -118, 90^ 3,3 light catalytic cycle oil b. 1+50-600 S.002 3 - 100 25-79 '.002 3-20 3 - 100 3-20 3 - 100 67-83 8O-7 I 86-71* 75-71* 0.Oli.01 ' 0.02X i 0.03.01 : -l*-*.02 i 0.10 1.1 3 - 20 3 - 20a 3 - 20S 2 - 203 1 - 20* 3 100 a 3-5 3 20 s 3- 20 2/month100 77-27 0.11X , 88-28 IOO-25 *li+ - ! o i . 91- 1*0 0,ll*i.02 ^ 95-1*5 n i 7 + *01 '17-.02 100-25 I o-is*:8! 92- 31* ! 0 .1 S i ; 8 f 100-27 0.13X ' 100-26 1 -11*-'.02 1 100-50 0.32-.0? ; 2/month100 2 - 100 81-85 96-30 . u * - 01* ! *12-.03 1 n i a + *02 ' *16-.01 . _L Approximate age of mice at start of experiment, 27 weeks, * Approximate age of mice at start of experiment, 23 weeks, * Approximate age of mice at start of experiment, 20 weeks, * Approximate age of mice at start of experiment, 11* weeks. TABLE I M - potency op various fractions from the REFINING OF PETROLEUM API ,, sample VIJMBER * FRACTION pr&ctic nal distillation (30 Alunni -- Fraction from API-8 3-6 0-9.3^ X c^7 9.3-19.^ 1 plate ESTIMATED SCHEDULE CORRECTED OF BOILING APPLICA- RANGE p TIONS (in F.at )no./week 760nun. ) - mg.) INCIDENCE OF TUMORS (Ji-weeks] 1+35-560 560-630 2 - 100 2 - 100 O-06 0-71+ RELATIVE CARCINO GENIC POTENCY, PMC - 5-8 19.U-30.3#1 3-9 .30*3-39.8^ X 3-10 39.8-4.9 ,6#1 3-11 1+9.6-59.2X . 8-12 59.2-69.I#1 630-695 695-710 710-765 765-800 800-830 2 - 100 2 - 100 2 - 100 2 - 100 2 - 100 0-71+ 56-o2 91+-1+1+ 90-33 93-28 - ^ 0.07 0,10-.02 0 *li+-.02 0 .21 .03 Diels-Alder Reaction fl-12a Non-adduct from reaction (95.W of API-9-12)1 2 - 100 100-26 0.23-.01+ Hractional distillation (30 plate column) `Fraction from API-8 3-13 69.1-79. SfBl 6-11+ 78.5-80.Qf* 3-15 Residue; 80.8-100ji5 8-18 !Proportionate reblend of distillation fractions, 8-6 through 8-15 830-650 850-875 >875 2 - 100 2 - 100 2 - 100 1 - 100 79-25 92-35 87-39 0 .1 7 - .02 X 8-26a *26b 1Aromatics from API-8 j26.5-3O.85i 1 j3O.8-3 2 .O5i a 61+1-61+6 3 - 10 0-76 - 61+6-651 3 - 1 0 0-76 - 8 - 2 6 c |32.0-3J+.li 1 651-656 3 - 1 0 0-76 - 8-26d 31+.1-36.0J 1 656-662 3 - 1 0 0-76 - j , $Qfz solution in benzene. , 33-3^ solution in benzene. Analysis indicated a content of .85# BP. $0% solution in benzene. Analysis indicated a content of 2.0^ BP. API 06494 1 . -'ICGSIC POTENCY OP VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM *`________________________ _______ _______ _______________ sampi-b hjmber DESCRIPTION OF EXPERIMENT ESTIMATED SCHEDULE CORRECTED OF BOILING APPLICA RANGE TIONS ;in F.at 'no./week 76O mm.) - mg.) INCIDENCE OF TUMORS ($-weeks) RELATIVE CARCINO GENIC POTENCY, PMC 8-26 8-2M 3-26g 0-26h 8-261 3-26 j 0-26k 36.0-33.0$ X 3 8 .0-U0 .051 U0.0-U3.95i1 U39-U6.0$ 1 U 6 .O-5 0 .35i1 50.3-52. Sfc1 52.5-5U8$a 0-261 5U.8-57.3^1 0-26m 8-26n 57.3-6o .U^S 60.U-62.U5i1 662-668 3 - 1 0 O-76 - 668-67U 3 - 1 0 7-U2 - _ 67U-686 3 - 1 0 20-72 - 686-693 3 - 10 12-25 - 693-709 3 - 1 0 36-61 - 709-717 717-727 727-736 3 - 10 3 - UO 3 - 10 25-U1 83-19 55-38 0.21X - 736-7U7 7U7-759 3 - UO* 3-10 93-35 100-39 O-^-ioy -17-:o 7 Contribution of accelerators to above fractions 8-26-2 0.17$ BP in 80$ saturates through alkynaphthalenes fraction of 8-26g, h, and i, and 20$ benzene 0-26-3 0.17$ BP in 80$ 3-ringed aromatic fraction of 8-26g, h, and i , and 20$ benzene ' 3 - 50 3 - 50 100-19 100-26 -i9i:S2 Air 0x3.dation (cobalt naphthenate catalyst) 8 FCC cracked residuum (prior to oxidation 83 83-1 Product of 2 hour oxidation of API-8 Product of U hour oxidation of API-8 2 - 100 2 - 100 2 - 100 9U-14 100-17 9U-17 .95-1^3 O.39X o .U 5 x 8-22 69$ aromatics of API-8, 31$ sec.- amylbenzene 83-2 69$ aromatics of API-83, 31$ sec.- amylbenzene 1 50$ solution in benzene. * 50$ solution In dodecylbenzene. * Painting discontinued after 10 weeks; 1 - 100* 1 - 100* 63-39 79-U5 20 weeks. 0 .20X u* ^ -.0 7 TABLE I (page 15) _NCGENIC POTENCY OF VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM API * 3A|iPLE kuSber DESCRIPTION OF FRACTION wftterials regenerated from Diels-Alder fttions (Maleic anhydride extraction) SCHEDULE OF APPLICA-] INCIDENCE TIONS OF [no./week TUMORS - mg.) ($-weeks] RELATIVE CARCINO GENIC POTENCY, ?MC Material from 1st adduct formed (2.7$ of API-8), 1$ In benzene Material from 2nd adduct formed (1.8$ of API-8), 1$ In benzene Material from total Class B 1 adduct (1.6$ of API-8 ), 1.5$ in benzene Material from total Class A 1 adduct (3*5$ of API-8), 2.2$ in benzene Chromatographic fractionation of extract similar to 8-23h________ Crystalline material from 1st frac tion (.15$ of API-8), .34$ in benzene Crystalline material from 2nd frac tion (.17$ of API-8), .34$ in benzene Material in mother liquor from 8-23a and 8-23c (1.5$ of API-8), 1.5$ in benzene . Third fraction (.4$ of API-8), .8$ in benzene Fourth fraction (.33$ of API-8), .57$ in benzene - Fifth fraction (.37$ of API-8), .57$ in.benzene. 26n-l Total material from 8-26n, 2$ in 50$ benzene, 50$ dodecylbenzene 3-50 0-8 [lClass A adduct was that normally soluble in 5$ aqueous NaOH; Class B adduct was not soluble in either 5$ aqueous NaOH or benzene after hydrolysis. fainting discontinued after 30 weeks; 37 weeks; * 32 weeks. API 06496 TABLE I (page l) . jOGSNi: POTENCY OF VARIOUS FRACTIONS FROM THE REFINING- OF PETROLEUM API sample fljMBER DESCRIPTION OF FRACTION SCHEDULE OF APPLICA TIONS no./week - mg.) RELATIVE INCIDENCE 'CARCINO OF GENIC TUMORS POTENCY, (-weeks) PMC 89-1 Anthracenic chromatographic fraction (1.6^ of API-89) of material from total adduct, 2% in benzene 89-2 Remainder of chromatographic frac tions (mixed anthracenes, benzanth racenes, etc., 0.2% of API-89), .5$ in benzene j 3 - 15 3-10 0-71+1 <0.02 100-68 0.03t. 01 120-1 Material from naphthenic distillate, 3 - 2 0 0-1+ - API-120, corresponding to API-89-2, 2;% in benzene jolvent extraction with cone. HBSOft 8-19 $0% extract* from API-8-10 and 8-11, 50% benzene s 2 - 100 22-32 8-20 $0% raffinate* from API-8-10 and 8-11, $0% benzene 2 - 100* 83-25 23-1 Q0% extract from API-23, 20% benzem . 2 - 100* 90-26 23-2 Q0% raffinate* from API-23, 20% benzene 2 - 100* 100-1+1+ <0.09 A-'O.I 0.2l4:o 0.13.02 Fractio nation of API-12 12-7 3Off non-adduct of Diels-Alder reaction on raffinate from sulfuric extraction of aromatic fraction b. 'v 680-780*, 7 0 % benzene 12-8 Ditto from fraction b . ^ 780-950 70% benzene 2 - 20* 2-15 77-65 90-58 0l+-.02 0.071 * Accelerators removed prior to extraction and reblended proportionately in extract and raffinate. * Painting discontinued after 21+ weeks; 4 1+3 weeks. ii API 06497 TABLE I (page 17) ..-^ISOGENIC POTENCY OF VARIOUS FRACTIONS FROM THE REFINING OF PETROLEUM A?I ,, SAMPLE ! jfljjtBER DESCRIPTION OF FRACTION SCHEDULE OF APPLICA TIONS no./week - mg.) RELATIVE INCIDENC]: CARCINO OF GENIC TUMORS POTENCY, (-weeks) PMC osraphy l .a 8-13 First aromatic fraction, 2% of API-8-13 3 - 20* 9-36 c o . 05 8-13b Second aromatic fraction, 2.1+J of API-8-13 _ ,* 8-13C Third aromatic fraction, 0 . 7 % of API-8-13 3 - 20* 1U-58 3 - 2 0 100-1+2 C O . 03 0.07X 8-13d 8-13 8-13f Fourth aromatic fraction, $ . 6 ) ( * of API-8-13 J| Fifth aromatic fraction, 56$6 of API-8-13 g Sixth aromatic fraction, 2% of API-8-13 8-13g Seventh aromatic fraction, 16.9J6* of API-8-13 . 3-20 3-20 3 - 20* 3-20 IOO-29 86-1+0 83-1+5 100-27 0 .10.02 0.07X 0.11X B-l3h Eighth aromatic fraction, 2.1+j6*of API-8-I3 g 8-131 Ninth aromatic fraction, 6.9/6 of API-8-13 3-20 3 - 20 100-37 73-36 0.09X 0 0 .1 .+ 00 U> M 71-2 Proportionate reblend of all frac tions from API-71 71-1 Reblend of all fractions except 71-1 dark resin proceeding aromatics 1-20 93-59 1-20 03-61+ 1 - 100 IOO-15 0*22i3+-.*0062 n*i16A"-*".G01l+ O.9OX i Proceeding colorless non-aromatic fraction, l+8j6 of API-8-13, proved to be a non-accelerating solvent when diluted 5Oj6 with benzene. See API-266 on page 3 of Table VII. Tested at this percentage in benzene. Painting discontinued after 35 weeks; * 1+1 weeks, API 06498 TABLE II CONTROL EXPERIMENTS WITH VARIOUS SOLVENTS API EXPERI MENT number 80 95 221 221a 22k 22 8 22 8 214-1 29k 29k* 639 SOLVENT SCHEDULE OP APPLICA TIONS Cno./week - mg.) STRAIN OP MICE MAXIMUM INCIDENCE OP TUMORS ()6 - weeks) INCIDENCE OP OR OSS CARCINOMA - weeks) White oil (95SSU) 3 - loo1 C3H White oil (95SSU) 3 - 100* CPW Dodecylbenzene 3 - 100 C3H mm0 8-81;% fraction b. 1 C3H 5U8-572 from dis tillation of API-22] Sec.-amylbenzene Benzene Benzene Distilled water 3 - 100 CFW 3 - 100 C3H 3 - 100 CFW 3 - 1004 C3H m0 Dodecane 1 C3H Dodecane for 12 3-50 C3H weeks followed by 70^ dodecane, 30% 3I4QSSU white oil 75/6 dodecylbenzene 1 mO C3H 2$% benzene 0-80 0-80 33-37 0-52 18-59* 0-100 0-62 7-78 0-80 0-82 0-80 0-80 0-52 0-52 0-82 0-100 0-62 7-78 5 0-80 0-82 U-15 0-I9 a Painting discontinued after 60 weeks; 31 weeks; 61 weeks. Histopathologieal examination confirmed only one of the four gross k lesions as a papilloma; the others were termed hyperkeratosis, 5 Histopathologieal examination showed one fibrosarcoma in 70 weeks. API 06499 TABLE III 1 ^ H lffiN TS INVOLVING THE APPLICATION OP SOLUTIONS OF METHYLCHOLANTHRENE IN VARIOUS SOLVENTS UPON THE SKIN OP C3E NICE -- API gXPERl" ItENT gtJHBER SOLVENT SCHEDULE OP CONCEN APPLICA TRATION TIONS ( % by (no./week weight) - mg.) MAXIMUM INCIDENCE OF TUMORS (-weeks) RELATIVE CARCINO GENIC POTENCY, PMC 218 Crude residuum, API-5 625 API-80, 95 SSU white oil 0.31 0.10 621+ API-80 0.20 293 31+0 SSU white oil 0.50 607 5056 benzene, $0% 0.10 31+0 SSU white oil 281 Cottonseed oil 0,0i+ 291 Cottonseed oil 0.50 21+6 Naphtha, API-1124 0.21 21+6 21+8 Naphtha,API-110-1 0.21 223 Sec.-amylben^ene, 0.09 API-221+ 222 API-221+ 0.18 231+ API-221+ 0.35 235 API-221+ 0.70 608 Decalin 0.08 609 Dinonylnaphthalene 0.08 3 - 100 100-30 0.09i.01 3 - 1 0 100-32 0 .lot. 01 2-10 3-20 3-10 95-32 100-20 93-38 3 - 100 3-20 3-20 3-20 3-20 3 - 100 89-69 95-23 100-22 100-21 100-22 81-1+6 0 ,1 5-.02 0.16X U0 ,U0Q'-+.*0 ^2 0.03t .01 n*1177^-".*0 6 0.19.02 0 .19 1.0 2 n )l+.02 0 ,lb - .o i 0 .01+1 . 01 3 -~100 2 - 100 2 - 100 3 - 50 3 - 50 100-1+1+ 100-27 100-19 92-1+51 88-56 o . o9 !: 2 0 .27! ; ^ 0 .28 1.03 o.ol+x 0 .0 5 1 .0 1 1 The pattern of response to the irritational effects of this solution was similar to that observed with dodecylbenzene. API 06500 TABLE IV IMENTS INVOLVING THE APPLICATION OF SOLUTIONS OF 3ENZ0PYRENE IN NON-ACCELERATING SOLVENTS UPON THE SKIN OF C3H MICE A fl ^NT HtjNBER 602 6014 299 296 282 21*14 2I4I4 252 252 252 252 613 613 28$ 286 SOLVENT n-octane Isooctane 3I4.O SSU white oil 31+0 SSU white oil Benzene Benzene Benzene 85/S b-methylnaphthalene, 15^ benzene Cottonseed oil Cottonseed oil SCHEDULE OF MAXIMUM CONCEN APPLICA INCIDENCE TRATION TIONS OF ( f b y (no./week TUMORS -weight) - mg.) | jf-weeks) 0.21 0.15 0.08 3 - 100 3 - 100 3-5 100-36 100-31 96-14-3 RELATIVE CARCINO GENIC POTENCY, PMC o .o e t;! 0.10.01 0.0l*.01 0.20 0.08 0.17 0.32 0.32 0.32 0.32 0.20 0.50 1.0 3 - 50 100-36 3-20 3 - 100 3-20 3 - 100 3-20 2-20 1-20 2 - 15 2-50 3-20 3-20 100-50 100-33 91+-37 100-26 100-27 9l4-51l 96-1*3 100-1+0 -100-37 100-32 95-25 0.081*02 0.07-.01 0 .09.01 0.07X 0,13-,02 0.10X 0.10X 0.15X 0.08.01 o .io x 0.09X .0.12.01 T ] f1 TABLE V EXPERIMENTS TO DETERMINE THE POTENCY OF MIXTURES OF POLYCYCLIC HBYDROCARBONS IN TECHNICAL NHITE OIL FOR THE SKIN OF MICE API EXPERI MENT MEMBER " HYDROCARBON b2k Me thylcholanthrene control 623 Me thylcholanthrene Benzopyrene 625 Methylcholanthrene control 626 Methylcholanthrene Benz anthracene CONCEN TRATION by weight) SCHEDULE OF APPLICA TIONS (no./week - mg) 0.20 2 - 10 0.10 0.20 0.10 2-10 3-10 0.10 0.20 3-10 MAXIMUM INCIDENCE OF TUMORS - weeks) RELATIVE CARCINO GENIC POTENCY, PMC 95-32 0,15-.02 100-26 0.17*.02 100-32 0.10*.01 IOO-3I4. 0.08X TABLE VI -gjjiENTS INVOLVING TEE APPLICATION OF SOLUTIONS OF METHYLCHOLANTHRENE (MC) IN DODECYLBENZENE* UPON THE SKIN OF MICE . API gjCPSRl*ENT DUMBER CONCEN TRATION ( i fey weight) STRAIN OF MICE SCHEDULE OF APPLICA TIONS (no./week - mg) MAXIMUM INCIDENCE OF TUMORS (jf - weeks) RELATIVE CARCINO GENIC POTENCY, ___PMC fmc OF MC 221 0 C3H 221a 0 C3H 226 0.006 C3H 226 0.006 CFW 225 0.012 C3H 225 0.012 CFW 213 0.05 CFW 211 0.12 C3H 211 0.12 CFW 208 0.15 C3H 21*9 0.17 C3H 21*9 0.17 C3H 212 0.35 C3H 3 - 100 3 - 508 3 - 100 3 - 100 3 - 100 3 - 100 3 - 100 3 - 100 3 - 100 3 - 100 3 - 100 3-20 3 - 100 33-37 0-52 50-1*0 1*1-51* 81-1*3 100-51* 100-18 100-22 100-17 100-15 100-12 89-11* "100-18 s - 0.05X A/0.03 SiS 0.30 U.36-.12 A^0.30 0.33 .03 0 )i7+08 u,43-.07 0 7c+06 *35-.oi* 0 7+*06 u *35_.o9 m 1*17 /v250 a/600 292 ^250 220 252 206 100 -- ___________ 1 Product obtained by alkylation of benzene with the propylene tetramer (aluminum chloride catalyst). Painting discontinued after 31 weeks. " ` ivldence of invasive mallgnaQpT, API 06503 TABLE VII n ACCELERATING a c t i v i t y o p v a r i o u s s o l v e n t s o n r a t e o p i n d u c t i o n OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE API gjCPSBliNT SOLVENT CONCEN TRATION (% by weight) SCHEDUIE OF APPLICA TIONS (no./week - ag.) MAXIMUM INCIDENCE OF TUMORS % - weeks) RELATIVE CARCINO GENIC POTENCY, __ Im c ____ n-octane n-decane dodecane 0.08+ ..0023 o i10 - .0012 cetane (chromato graphed- on siile gel) n0 .1114+- ,0032 70 n-hexadecene-1 rVHLOPARAFFINS Decalin Cyc1ohexylde cane 7 -cyclohexyltri- decane, PSC-504 3-40 100-25 0.19'+..0043 100 0.04X * 22-!o 4 n 1 02 , -, 0 . 1 5 - ,oi ^5 0.09*.01 o.09.oi 0.09.02 0.1U 0.Ili.01 Carcinogen in this case was methylcholanthrene. * The pattern of response to the irritational effects of this solution API 06504 TABLE VII (page 2) ACCELERATING ACTIVITY OP VARIOUS SOLVENTS ON RATE OF INDUCTION OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE API gXPERl- IftjMBgL SOLVENT A ctions from 2 rjgmTT.rJtTIONS OF API-80 Percent Boiling API-80 Range O-3 .5 SCHEDULE OF CONCEN APPLICA TRATION TIONS ( % by (no./week weight) - mg.) 0.17 3 - 5 0 MAXIMUM INCIDENCE OF TUMORS [% -weeks) 100-22 0.17 3 - 5 0 100-22 0.17 3 - 5 0 100-22 0.17 3 - 50 100-32 8.7-16.7 625-614.5' 0 .1 7 3 - 100 91+-21+ 276-Q U . 7 -19.5 61+5-655' 0.17 3 - 100 100-28 ^5.7-36.3 61+0-685' 0.17 3 - 100 100-30 L9.5-30.3 655-675' 0.17 3 - 100 100- 21+ 276-10 )0.3-1+0.5 675-700' 0.17 3 - 100 100- 21+ 276-6 276-6 36-IOO > 700 0 .17 (residue purifiei by percolation through silica ge ) 3 - 100 3 - 50 j 100-29 92-29 RELATIVE CARCINO GENIC POTENCY, PMC o .i6!;o J 0.15*.03 0.08.01 0 . 1i+.02 0.11X 0. 10*.01 0-l4i:o3 00 # 1H1 -+.*012 o.ioi.oi 0.09X P *MC OF BP 88 88 i|7 82 65 59 82 65 59 53 FRACTIONS FROM DISTIL LATION OF SATURATED COM PONENTS OF TCC RESIDUUM, API-71 Percent Range 0-2.9 4-30-500' 6.1-7.1+ 550-565' 7 .+-11.3 580-600' Ll.3-i5 .l4. 600-620' 0.18 0.18 0.18 0.18 3-30 3-20 3 - 1+0 3-50 88-17 83-I8 100-25 100-27 + .06 22-.01+ 122 0,i2iR3+-.*1^0 128 - ,-+.06 *17-.o5 9k 0 T2+*^2 67 TABLE VII (page 3) a c c e l e r a t i n g ACTIVITY OP VARIOUS SOLVENTS ON RATE OP INDUCTION OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE r------ API SXERIHSNT HUMBER ' SOLVENT CONCENTRATION by .weight) SCHEDULE OP APPLICATIONS (no/week - g.) MAXIMUM INCIDENCE OP TUMORS (j6-weeks) RELATIVE CARCINO- GENIC POTENCY, PMC 0 PMC OP BP 1 9 AlPesIs-8-f2r1a+,cticoonlor 0.21+ 1 - 5 0 100-1+3 0.15*.02 63 from chromatog raphy of API-8 2b6 50ji colorless fraction from 0.15 3 - 100 100-31+ 0.07*.01 1+7 chromatography of API-3-13, $0% benzene aleylbeiJZENES 605 Diisopropylbenze i 0.17 3 - 5 0 100-1+7 0.05t . 01 29 275 Triisopropylbenzene 275 606 t-octyltoluene 0.17 0.17 0.17 3-50 3-30 3-50 100-18 0 22+,(^ 130 * 03 100-30 0.12*.02 71 100-21 0.17X 100 262 1-phenyldecane 629 Dode cylbenzene (DDB) 21+5 DDB 0.18 0.08 0.17 3-20 3-20 -- 3 - 100 95-16 75-30 100-19 -33;3 183 o.ii+t!o \ 180 . ->+.08 *30-.o 6 176 21+5 3-20 100-31 0.16*.05 91+ 21+5 3 -5 100-23 0.19*.01+ 112 LAB DIS:'ILLATION OP COMMERC:CAL ALKYLATES Distillation of Alkylbenzene1 271+-8 Fraction b. 1+50 0.17 3 - 1+0 100-22 o.lSt-.ofc 88 500* 271+-13 Fraction b. 555560 0.17 3-50 100-12 o.UoYo l 236 L x Product of alkylation of benzene with polypropylene TABLE VII (page k) ACCELERATING ACTIVITY OF VARIOUS SOLVENTS ON RATE OF INDUCTION OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE API gjCPSRl- hsnt JIUMBER SOLVENT 267-1 Distillation of PDDB1 Fraction b,60361+2 267-3 267-5 Fraction b.655- 683 Fraction b.661j.730 267-8 Fraction b.659- 76O0 SCHEDULE OF CONCEN APPLICA TRATION TIONS ( i by ^no./week weight) - mg.) MAXIMUM INCIDENCE OF TUMORS \$ - weeks) 0.17 0.17 0.17 0.17 3-20 3-20 3-20 3-20 100-31 100-33 IOO-38 IOO- 3 6 RELATIVE CARCINO GENIC POTENCY, PMC____ . . n+.02 0.1 0 - ,0 1 0 .0 7 .0 1 0.06*.01 0 .07**01 PMC OF BP 59 1+1 35 1+1 alkylna:HTHALENES 613 85/6 b-methylnaphthalene, l5j? benzene 0.20 265 Butyl-dimethylnaphthalene 0.16 272 Monoamylnaphthalenes,b.570 0.16 273 Dlamylnaphthalene s 0.16 b.b30-690o 09 Dlnonylnaphthalene 0,08* 2-50 3-20 3 - 1+0 3-50 3-50 IOO- 3 7 100-25 100-19 100-19 88-56 0.10X oau!;gI 0 .1 7 .03 n0 .23A8+-.*018^ 0.05*.01 50 88 106 175 a 63 MIXTURE 3 OF ACCELERATORS WITH V!HETE OILS 260 5* DDB, 95* API-80 0.17 3 - 100 100-33 0.07*.01 1+1 259 2 0 $ DDB, 8 0 $ API-80 0.17 3 - 100 100-32 .o8t;2 1+7 33 5 0 $ DDB, $ 0 $ API-80 0.08 3 - 5 0 61+-37 rsj 0.06 75 637 l-- 50# DDB, 50$ AFI-80 0.17 3-50 100-27 0.10*.01 59 Alkylbenzene, residual by-product of commercial alkylation of , benzene with propylene tetramer. Carclnoeen In this case was methylcholanthrene, TABLE VII (page $) a c c e l e r a t i n g activity of various solvents on rate of induction OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE r"'--- API gjrpERl' uent SOMBER SOLVENT CONCENTRATION ( * by weight] SCHEDULE OF APPLICATIONS (no./week - mg.) MAXIMUM INCIDENCE OF TUMORS (*-weeks) 636 75* DDB, 25* API-80 0.08 3 - 5 0 100-27 638 75* DDB, 25* API-80 0.17 50* DDB,50* 31+0 SSU white oil 0.08 3 - 50 3-50 100-29 1+2-36 297 50* dodecane, 50* 0.20 3i+0 SSU white oil 297 297 611+ 75* dodecane, 25* 0.20 3i+0 SSU white oil 611+ 611+ 3 - 100 3-50 3-20 3 - 50 2-50 1-50 100-21+ 100-29 IOO-33 100-28 100-26 100-31+ RELATIVE CARCINO- GENIC POTENCY, Pm c 0.-+3- no n -P+.02 0.12-01 /VO.05 0.13.01 u *13-.o 3 0 .08.01 0.12t. 01 0 .1 5 ^ .0 1 n pn"*"*02 *0 -.01 O *MC OF BP 163 71 r j 63 65 65 i+0 60 75 100 MIXTURES OF DDB WITH aromatic HYDROCARBONS 628 50* DDB, 50* b- 0.08 3 - l+o . 93-32 0 .lit. 02 138 me thylnaphthalene ' 31+ 50* DDB, 50* benzene 0.08 3 - 5 0 95-23 o.n+i|oi 175 1+1+ 50* DDB, 0.09 3 - 5 0 68-13 - - 50* benzene 6I+3 50* DDB, 50* benzene 0.17 3 - 50 30-13 >-- API 06508 TABLE VII (page 6) ACCELERATING a c t i v i t y of v a r i o u s s o l v e n t s on r a t e of i n d u c t i o n OF TUMORS BY DISSOLVED BENZOPYRENE (BP) IN C3H MICE API EXPERI MENT number S0LVENT CONCEN TRATION ( % by weight) SCHEDULE OF MAXIMUM APPLICA INCIDENCE TIONS OF (no./week TUMORS - mg.) \% -weeks) i\ -O\ Vn-3 1\ IF **603 M E S FROM VARI0US GENIC 0ILS Fraction of TCC residuum, API-9, b. 01+0-600 0.16 3-50 100-30 RELATIVE CARCINO GENIC POTENCY, PMC bl5 Lagunillas dis tillate. b.550- 650 616 Lagunillas dis tillate, b. 650 690 0.16 0.16 3 - 50 3 - 50 100-16 100-16 0.35! : $ distill/ITES FROM CRUDE ASSAYS by BURE/ITT OF MINES'1 Corre 1Boiling Specific ation Range Dispersion Index 617 1+80-660 li+1 26 618 1+80-660 186 U9 619 1+80-660 161+ . 5k 630 1+80-660 151+ 31 631 1+80-660 190 53 d32 1+80-660 11+5 37 632a 50 PI-632, diluted $0% with benzene 3 - 50 3-50 3 - 50 . 3-50 3-50 3 - 50 3-50 100-21+ 100-19 100-19 92-19 100-18 95-19 5-13 0 .1i+.01 0.20.02 *20-.*02 0 .18.02 0.23*. 01+ 0.20-.8! - 61+0 1+80-660 11+1 21+ 3-50 26-13 - Diluted 50j6 with benzene 61+1 1+80-570 130 21 3-50 10-10 - Diluted $0% with benzene 61+2 570-660 138 23 3-50 Diluted 50 with benzene 11-10 PMC OF BP 88 169 219 78 118 118 106 135 116 - Experiments run at a concentration of 0.17^ BP. API 06509 TABLE VIII effect of early exposure to accelerating solvents on results OF SUBSEQUENT EXPOSURE TO CARCINOGENS ----- - API SXPER10KT SM3ER DESCRIPTION MATERIALS APPLIED TO MICE IDURING FIRST SIX WEEKS OF EXPERIMENT SEVENTH WEEK TO END OF EXPERIMENT STRAIN OF MICE SCHEDULE OF APPLI CATION OF iINCIDENCE CARCINOGBf OF (no./week TUMORS a - mg.) (Jf-weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (5J F.L. in weeks) EdJki 221 DDB* DDB 9 TCC resid API-9 uum,API-9 221-9 221-9 253-9 DDB PDB3 API-9 API-9 57 API-57* API-57 221-57 DDB API-57 208 API-208^ 221-208 DDB API-208 API-208 82 TCC resid API-82 uum, API-82 600 Dodecane API-82 601 3^0 SSU API-82 white oil C3H 3 - 100 33-37 C3H 3 - 100 100-1+7 36.23.9 C3H 3 - 100 100-21 11+.5-1.8 C3H 3 - 100 100-22 12.82.i+ C3H 3 - 100 91+-26 13 CFW 6 - 100 50-I6 - IOO-25 CFW 6 - 100 50-13 - 100-16 C3H 3 - 100 100-15 10.1+4.6 C3H 3 - 100 100-11+ 8.11 .1 C3H 1 -1 0 100-50 3!I C3H 1 - J.0 100-1+2 30.741+.0 C3H 1 -1 0 100-1+1 30.2*5.1+ 76 Reformer API-76 tar,API-76 620 Dodecane API-76 621 95 SSU API-76 white oil C3H 3 - 50 83-52 ^31+ C3H 3-50 C3H 3-50 67-1+8 55-1+5 ,n/33 1+3 622 31+0 SSU API-76 white oil C3H 3-50 60-1+7 35 Schedule of application of accelerator was the same as that of the carcinogen except In experiments 600 and 601 In which case $ 0 mg. was applied three times each week. Time measured from date of initial painting with carcinogenic material. Dodecylbenzenes obtained by DDB obtained with propylene alkylation of benzene with tetramer; 2-phenyldodecane 12-carbon olefins (PDB) obtained ; with 1-dodecene. Filtrate oil from pressing of Midcontinent paraffinic distillate. Solution of 0,l5ji methylcholanthrene_Jja_dodecjlbaaaan______ AP! 06510 TABLE IX EXPERIMENTS to determine the carcinogenic promoting activity OP VARIOUS MATERIALS FOR THE SKIN OP C3H MICE CARCINOINCIDENCE TIME GENIC OP TUMORS OP 2nd PROMOTER INITIA PROM APPLICA USED API TOR, SINGLE TION PROM 3rd jgCPERl" SINGLE APPLICA(if appli-' Hk RK jfiSNT APPLICA TION cable) TO HUMBER __ TION (Jf-weeks)(wks.-mg.l END SCHEDULE OF APPLI CATION OP PROMOTER |no./week - mg.) MAXIMUM INCIDENCE OP TUMORS (-weeka) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION {5jC P.L. in weeks) 229 100 mg. 13-13 none none - API-229' 1 3 -61+ - 23O 100 mg. API-229 none Dodecylbenzene, DDB 3 - 100 92-31+ 1 1 .8^2.8 231 100 mg. API-8, O-63 none FCC res iduum none O-63 232 100 mg. API-8 239 100 mg. API-8 none DDB 3 - 100 50-26 21+X none Distillei 3 - 1 0 0 0-76 - water 21+0 100 mg. API-8 none API-80, 3 - 100 0-76 -- 95 SSU white oi] 29O 100 mg. k -2 b 28-100 none . - API-290 95-59 . rO 1+6 287 100 mg. API-290 288 100 mg. API-290 0-28 none 28-100 Alkylbenzwne, partly DDB API-80 3 - 100 3 - 100 79-30 96-57 17^ 1+8 289 100 mg. API-290 0-28 28-100 31+0 SSU 3 - 100 white oil 89-72 /x/ 50 292 100 mg. API-290 292 292 none Dodecane 3-50 2-50 1-50 91+-26 94-53 81-59 u!2 . aC i 1+1+.0+3 . 9 Solution of 0.5 g. dimethylbenzanthracene in 100 ml. aec.-amylbenzene. Solution of 0,5 g. dimethylbenzanthracene in 100 ml. 3l+0 SSU white oil. API 06511 TABLE X EFFECT OF TERMINATION OF EXPOSURE OF C3H MICE TO CATALYTICALLY CRACKED OILS AT A CRITICAL PHASE OF THE EXPERIMENT API gXPSR1" jffiNT UMBER... W-l DESCRIPTION OF EXPERIMENT Dewaxed oil from catalytic ally cracked re s iduum SCHEDULE OF APPLICATIONS TOTAL (no./week NUMBER - mg.) OF WEEKS 2-20 1 W -1A Ditto 43-IB Ditto 2-20 2-20 10-19* 9 1 71 TCC residuum 2-20 71A Ditto ` 7IB Ditto 2-20 2-20 lil-25* 12 MAXIMUM INCIDENCE OF TUMORS {%-weeks) AVERAGE LATENT PERIOD FOR TUMOR INDUCTION (5* F.L. in weeks) AVERAGE TIME FROM PAPILLOMA TO GROSS CARCINOMA (weeks) 914-- 17 12.7-1.14 114 100-19 1 3 .8-1.2 16 16-12* - - 100-27 18.5-1.3 15 100-25 18.3-1.5 16 53-18* Painting continued in each mouse until gross evidence of malignancy in that mouse. Painting of each mouse discontinued at time of appearance of papilloma in the individual mouse. No additional tumors developed up to the 23rd week at which time appli cations were resumed. They were terminated in the 28th week after the appearance of a papilloma in an additional animal. All survivors had developed tumors by the 58th week. * Procedure similar to API-I4.3 -IB. Painting resumed at 30 weeks, discon tinued after 32 weeks. By the 61|.th week all but one of the survivors had developed tumors. Gross malignancy was evident in 58% of the mice. API 06512 TABLE XI EXPERIMENTS TO DETERMINE TEE POTENCY OF CERTAIN POLYCYCLIC HYDROCARBONS FOR THE SKIN OF C3H MICE API CPSRI0ST mJMBER HYDROCARBON 261 1;,5-dime thyl- phenanthrene SOLVENT Benzene 627 Benz Ca]anthracene Dodecane CONCEN TRATION ( % by weight) SCHEDULE OF' APPLICA TIONS (no./week - m g .) MAXIMUM INCIDENCE OF TUMORS (J? - weeks) 0.86 m 1 0-814. CoVJ 0.50 ion 53-1*5 ' API 06513 TABLE XII EXPERIMENTS ON THE RETARDATION OF TUMOR FORMATION BY WASHING CFW MICE PERIOD OF EXPOSURE TO OIL HATERIAL CPBRI- CARCINOGENIC BEFORE RE USED FOI ;AGENT ggNT OIL MOVAL BY INITIAL FOR DUMBER APPLIED WASHING RINSE WASHING "U3 113 Industrial fuel oil, API-113 control (no -washing) none none AVERAGE SCHEDULE LATENT OF MAXIMUM PERIOD APPLICA INCIDENCE ?QR TUMOR TIONS OF [EDUCTION (no/week TUMORS f(5* F.L. - mg.) $-weeks) -in wks. 1 3 - 100 ' 94-36 A/ 16 3 - 1001 97-25 17.3*1.2 309 API-113 1 hour none 1letergenl 3 - 100 40-67 X solutior 31O API-113 4 hours none 1letergenl 3 - 100 54-57 56x solutior 311 API-113 4 hours 95 s s u .Letergenl 3 - 100 83-52 45x white o .solutior API-95 31* API-113 7 hours none 1Letergenl 3 - 1001 94-46 a /35 solution 12 FCC residuum ,control none API-12 (no -washing) 303 API-12 1 hour none }0k API-12 9 hours none 8 FCC residuum , control none API-8 (no washing) 300 API-8 10 min. none 301 API-8 1 hour none 302 API-8 4 hours none none 3 - 100 100-14 A/ 10.5 soap 3 - 100 solution soap . 3 -.100 solution ' 100-40 100-21 a/ 27 - V 17 none 1-100 100-26 12X soap 1 - 1 0 0 solution soap 1 - 100 solution soap 1 - 100 solutior 0-80 - 20-80 - 100-70 a/ 6 0 | ! 1 j Strain of mice used for this experiment was C3H. API 06514 TABLE XII (page 2) EXPERIMENTS ON THE RETARDATION OF TUMOR FORMATION BY WASHING CFW MICE API iYPERI" jCJNT nM3ER t 8 PERIOD OF EXPOSURE TO OIL CARCINOGENIC BEFORE RE OIL MOVAL BY APPLIED WASHING API-8 control (no -washing) MATERIAL USED FOR INITIAL RINSE none AGENT FOR WASHING none SCHEDUIE 1AVERAGE LATENT OF MAXIMUM PERIOD APPLICA- INCIDENCE ?0R TUMOR TIONS OF INDUCTION (no /weok TUMORS (5* F.L. - mg.) weeks) -in weeks' 3 - 100 100-9 ^ 8X 305 API-0 20 min. none <Letergent 3 - 100 solution 93-51 /vuo CO Or*~\ API-8 306 a p i -8 20 min. 1 hour API-95 none none <.etergent solution 3 - 100 3-100 IOO-52 9U-UU ^32 r J 33 307 a p i -8 1 hour API-95 letergent 3 - 100 85-33 5 solution 312 Barrier cream applied API-8 applied Removal of 0il by washing with detergent solution 313 ABParIr-8ierappclrieeadm applied API-8 applied Removal of oil by washing with detergent solut ion 9:00 AM 11:00 AM 12:00 AM 3 - 100 71-U5 a A O X 9:00 AM 11:00 AM 2:00 PM 1+t30 PM 3 - 100 100-31 v 25 ' API 06515 TABLE XII (page 3) EXPERIMENTS ON THE RETARDATION OP TUMOR FORMATION BY WASHING C3H' MICE ERIOD OP EXPOSURE API TO OIL MATERIAL gXPERI- CARCINOGENIC 3EFORE REUSED FOR AGENT jENT OIL MOVAL BY INITIAL FOR DUMBER APPLIED WASHING RINSE WASHING AVERAGE SCHEDULI LATENT OF MAXIMUM PERIOD APPLICAINCIDENCI FOR TUMOR TIONS OF INDUCTION ]no./weel TUMORS (S% F.L. - mg.) (jf-weeks) -in weeks 8 API-8 8 316 none 317 none 320 API-8 318 API-8 319 API-8 control none (no .washing] none none none 3 - 15 3 - 100 ietergen1;3 solutioi L 100-18 89-9 O-72 12.1+11.2 5.2.6 none a p i -95 ietergen- 3 solution O-72 95 min. 95 s s u ietergen-;3 - 100 white oi] solutioi L API-80 95-16 10.011.2 75 min. 3*4-0 SSU ietergen-3 - 100 white oi] solutioi 1 85 min. refined ietergen-;3 - 100 kerosene solutioi 1 100-21 91+-21 16.6*1.1+ 16X 56 ?eed to Wax control none none 3 - 2 0 84-51+ 32X ?ressing, (no 56 a p i -56 -washing] 3 - 100 65-1+2 21+X 311+ a p i -56 7 hours none ietergen-3 - 100 67-7*+ 55x solution -