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j m'd fi'. "-,v'! .mr,'-,7-rr ,:~ Miss C. Elan .... m~ lw ° ° ..... ,-r~ SRE/PSB/46D-2 (Battelle) D,'~T£ S.R., Evelyn 3rd June, 1977 TABLES EX RD.14SI RESTRICTED Please prepare, for transmission tolBattelle, masters of the following ratifies from the above report. Page numbers should be deleted. Page 15 AE~Dendix 1''/ / Page 16 Appendix 2, including tenet Pages 51-62 Tables 33 to 44/ Pages 70-73 Tables 52 to 73 Please include the equations under tables 36, 37, 55 and 56 but do not include the text associated with the other tables. If possible, it would be helpful if the table numbers could be preceded by an "A" to become Tables A33-A44 and A52-A72. S oRo EV~YN ~D BAT Co LTD - MINNESOTA TOBACCO LITIGATION

[ I i I I ~RT TITLE: i J..'.l,:;..," u ,ll.,~J.I'~:. .. ~. ..u .... ; , ..... :'. t PROJECT JOB NO. : :,l ~, 5. " ~ FILE NO. : i" i.. b.. ,). AUTROR: ' J ": ~O~LKa.D~: ISSUE~: ~ u ,. DISTRIBUTION: SJC (~) : !~-"_: (~_) ." .'_tZ ~2> ~ ,~.,~ (l) . ..... '~) "" - 2_S .'i) -,'~ ~i) : C-TP a_. =_ (!) " DGF'~. : Library (2) TAPE P EF:1%q Check Li8% BindAn~: Z~/Qra~ No. : Photo#raphl No. : Re@uctlons: Total Pa~s: -)~" I "2,) C-"; : ~ (L.) Draft for typing (1) (4) (5) Prepa2e mlM~ter: Co=rect£on~ (i)' (2) wpare 1 Bound Co~J l~ue : Typing Cheoking D~te l~te Sent Reed / D~te Returned mu~J Author f/ S. B. z~ .-4-', v , ~.~ ic Z~te 7.z.77 '3~,,q7 Ii~.%er X~to This pro forma is intended to facilitate and detail the pro~m'eaI of @.R. A D.C. Repor~8 from the typescript 8ta@~ until ~hezepoz~ Am finally &ppx~ved and imR@d. ~ho~'~ f~T~ • hould ~e commenced a~ the time of the in/tial ~in~a~d ac=~E~ ~he 'ty'poIc:L'ipt (~ master ~er preparation) at all ~ubsequent eta4~e. It mASt be sen% to cemtz~.l filAngvith the master when the report Is iSmAed. Not.._ee: I. ~herever po88ible, dz~ft8 ~or %-yping ~hould bo wzltton in ink. ~. After i-/pin~, the ~I~ipt 8h,mala normally be re~ %0 the Au%~c~, 'who will eubIe~uently obtain~he Group Leader'I and Zs~ue~oe appx~wal. Circulation ~hould be determined by the Ie~aer. 4. The typescript mu~t not be premerlt~ for printing ~A%til ~e limaor ham AxtAtl~%le~ %he p~ fcrm~ a@aAn~% "Prepare Ma~ter". 5. After printing, one bound copy mast be returned to %he eerier for fiz~l &l~,~&l and ~he Issuer will ensure that one copy iI ~een by ~he M&na~r. BAT Co LTD - MINNESOTA TOBACCO LITIGATION O (.j-n -..-..4 o

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A STArXSTXCAL ,.~Ys~s oF THE Wc~E.C~ OF REPORT NO. RD. l&81 RESTRICTED 22.4.1977 AUTHOR: E.~. Wilkea ZSSUED BY: N.E. Willis ¥ROG. EEF. 11.0S.01 DISTRIBUTION : Dr. S.J. Green Dr. D.C. FalCon L~bc&ry Copy No. 1 " " 2, 3 " " 4, 5 COP~NO: BAT Co LTD - MINNESOTA TOBACCO LITIGATION i r,,o

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ZBWII2~IA6~-2 Group Research & DeTelopment Centre, British-American Tobacco Co. Ltd., SOUTHAMPTON. 22rid April, 1977 I A SZATISZIC~a.~SIS OF T~ n~C~D~C~ OF I"L~OUR-BEARING ANINALS ZN JANUS F..XI~ER~ B9 CReport No. KD.2481 Restricted) SU~IARYI The major conclusions to be drawn from th~s analysis are:- 1. Ethanol extraction reduces the tumor£aeniclty of the control tobacco. 2. Return of the material extracted by the ethanol to the tobacco does not completely restore the tumorigenicity of the control bland. Canadian PCL v£th "Garlach" additives has a lover tumorisenic activity than the extracted tobacco. Gerlach sheet has a lower tumorigenic activi=y ~han the Canadian PCL containins "Gerlach" additives. Gezlacb sheet prepared from ethanol extracted tobacco has a very low activity, and the effects of ethanol extraction and the Getl&ch process seem to be additive. 3~ , S, NOTE A copy of this report with Sugary I and Appendix lII deleted has been passed to the Battelle ~t£tute. Frankfurt-anr-Nain. for incorporation i~ their report. BAT Co LTD - MINNESOTA TOBACCO LITIGATION w

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Zm,;/L~/46D-'2 Croup Research & Development Centre, Brltlsh-America-- Tobacco Co. Ltd., SOUTKkMmT0~. 22nd &priZ, 1977 A mV.L SXS n c cz (B, mport lqc. 1~.1481 ~ecric:ed) SUMHAEY The major conclulons to be drawn fro: this analys£s ate:- I. The extracted tobacco has a lower tumorlgen£c activity ~ the control blend. 2. Return of the extracted material to zhe tobacco does not completely restore the cumor£ien£c activity. 3. Sheet ucar£al 'A' has a lower tumor£Sen£c act£v£Cy :ha- ax:ractad tobacco. Sheet macer~al 'B' has a l~r tumor£gen£c acc£v£ty rAum macar£al 'A'. 5. Sheet materLAl 'C' has a lower Cumo=£semic activity cha: matar&al 'B'. Gr~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION

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-2- 1. OBJECTIVES The objective of this experiment was to com.,are the effect of several alternative modes of tobacco manufacture on the tumorigenic activity of the condensates produced by ciKarettes containing these materials. A subsidiary objective was co compare these data with an earlier JANUS experiment (B3). Unpainted mad acetone painted control Kroups of animals were also included in this ~etimenc. 2. DESIGN OF EXPEEIMENT Five modes of tobacco manufacture were used, as well as the 'conventional' method used to produce the control ciSLTette. The experimental treatments ware numbered as follows:- B9-1 Contro I cigarette. B9-2 Extracted tobacco. B9-3 Extracted tobacco. Extract returned. B9-4 Reconstituted sheet type 'A'. B9-5 Reconstituted sheet type tB'. B9-6 Reconstltuted sheet type 'C'. B9-7 Repeat of experiment B3. 39-901 Unpainted controls. B9-902 Acetone painted controls. Two condensate levels (40 ~ and 60 ~) were used for Erear~enna Bg-1 to B9-6. Only one dose level (40 mE) was used for B9-7. The condensate was applied three tiros each week th~ou&hout the perlod of the experiment in 0.3 ml of solution. The solvent used was acetone, so that B9-902 was painted three times per week with 0.3 ml of acetone. Thus the axperlment consisted of 15 Eroups of animals, each group BAT Co LTD - MINNESOTA TOBACCO LITIGATION m

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-3- containing 147 animals in the original design, a total of 2205 animals. These animals were unmated female albino mice of Cax-~or~h origin. ~hen submitted to the experiment they were 8 ~o 9 weeks old and weighed on average 20 K- All animals in the experiment were shaved with the same shearing rhythm. The de~ailsof animal husbandry and condensate production are to be found in (3). 3. RESULTS OF EXPERIMENT The practice at Battelle, Frankfurt, is to examine each anJmml weekly. Skin les~ons within the painted area are recorded as tumours if they have a diameter of 8c least 2 --- and protrude above the skin surface or have a firmer consistency than the surrounding skin. If at any subsequent examination a tumour is judged no have disappeared a regression is recorded. For the purpose of tabulating the incidence of tumours, the time of appearance of a tumour is taken as the time of appearance of che papilloma, recorded as described in the previous paragraph. The condition of malignancy is not diagnosed until autopsy; the time of onset of malignancy is zaken as the time of death of the animal carrying ~he tumour. Tumours are regarded as malignant if nhey produce metastases, or if they infiltrate the dermis and penetrate the tunlca muscularls~ or if they inf£1trate the dermis and penetrate the basal membrane of the epithelium. Occasionally tumours show infilnration of the dermis, but it cannot be clearly established that penenranion of uhe basal membrance had occurred. Such tumours were recorded as showing the first siena o£ malignancy but are now classified as benign (i.e. class 6 for animals and class & for lesions will be 0, see below). BAT Co LTD - MINNESOTA TOBACCO LITIGATION o

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-4- The results of the experlment are shown in Tables I to 15. These tables show the incidence of tumour-bearin8 animals in the 15 experimental Eroups of animals. The animals in an experimental Eroup may be allocated Co the followinE seven classes:- 1. Animals having no leslon. 2. Animals havinE lesions all of which permanently regressed. 3. Animals havinE lesions all of which are uncharacterised. 4. Animals havinE lesions, some of which permanently regressed, the r~mainder being uncharacterlsed. 5. Animals having at least one confirmed tumour. 6. Animals havinE at least one confirmed turnout showing the first siEns of maliEnancy, but no maliEnant tumour. 7. Animals havinE at least one malignant turnout. An animal must fall into one and only one oF the classes I to 5. Classes 6 and 7 are sub-divisions of class 5. The lesions borne by an animal in an experimental Eroup may be allocated to one of the followinE five classes:- i. "Lesions which permanently regress. 2. Lesions which are uncharacterised. 3. Lesions which are benisn. Lesions which show the first slgns of malignancy. 5. Lesions which are maliEnant. A lesion must fall into one and only one of these five classes. Zn order to analyse the incidence of tumour--bearins animals, Che time of appearance of tumour-bearLns animals in the experiment is tabulated as in Tables I to 15. The first column shows the duration BAT Co LTD - MINNESOTA TOBACCO LITIGATION ,",o

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-5- of the experiment divided into 4-week periods. The rimes recorded in the dace for each animal e.g. rime of appearance of tumour, eime of death, etc., are recorded in weeks. The second col,mm is defined as the number of animals aZive and tumourless at the beginning of the time period. The third column is defined as the number of animals becoming Cumour-bearlnK during the 4-week period. Column 4 is defined as the number of animals dying without becoming turnout-bearing during the A-week period. The fifth colu~-n is defined as the ~uanbar of animals alive without a malignant cumour at the beginning of the A-week period. The sixth column is defined as the number of animals which have no malignant tumour at the beginnlnK of the time period and which produce at leash one malignant tumour during the A-week period. Since the onset of malignancy is defined as the date of deaCh of an animal bearing a malignant turnout, colum~ six may be equivalentl7 defined as the number of animals dying with a malignan~ tumour during the 4-week time period. Similarly column 5 may be equivalently defined as the tonal number of animals alive at the beginning of the A-week period. The seventh colunm is defined as the number of animals dying without a maliEnanC Cumour during the A-weak period. Thus if the rows of che cables are numbered I to i then for colunms 2, 3, & and 5, 6, 7 Ni÷I = Bi - D1i - D2i where N. is the number of animals at risk et the beginning of time period i, DIi is the number of animals becoming tumour-bearing during time period i, and D2i is Che number of anLmals dying during cime period i wlChouC becoming cumour-bearlns. N1 is the number of anlmals enterln$ the experiment at the beginning of week 1. BAT Co LTD - MINNESOTA TOBACCO LITIGATION k.m

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-6- The ani~nals in an exPer£mental group enter the tables according to their occupancy of the seven classes described above. Thus animals from classes 3, A and 5 will enter column 3 of the cable; an£mals from classes 1 and 2 w£11 enter column 4 of the cable; animals in class 7 will enter column 6 of the table. Columns 3, 4, 6 and 7 are totalled. These cables £orm the basis of the statistical mnalysls. Subsidiary tables of the numbers of animals in the seven classes and of the numbers of lesions in the five classes, are shown in Tables 16 Co 30. Table 31 is a summary of Tables 16 and 17, and Table 32 is a su~=ary of Tables 18 co 30. It will be noted thaC Tables I to 15 frequently show chat the numbers of aninmls in the experimental groups were greater than those stated at the beg£nning of section 2. These extra animals are called "REPLACZHENT AHIHALS" and wez'e taken into the exper;,nent to replace animals dying during the first A weeks of treatment. The number of animals used in the 15 experimental Kroups were as £ollows:- B~l B~2 B~3 B~5 B~6 B9-7 Unpainted control Acetone control 40 mS 60 mg 1 1 2 1 0 O 0 5 0 10 1 3 11 1 1 A total of 37 replacement an£mals were used, mak£ng an overall total of 2242 animals used in the experiment. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢...m

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-7- The analys£s o£ the data of Tables I to 15 £alls into 3 sections:- (a) Analysis of the data from the untreated control groups. (b) Comparison of groups Bg-I to B9-6. (c) Couparisoa of B9-7 with the data from JANUS experiment B3. ANALYSIS OF CONTROL GROUPS No skin tumours occurred in either the unpainted control group or the acetone painted control group. Figures 1 and 2 show the mortality curves of these two groups and, for comparison, the uortality curves of the equivalent groups from experlmenC BO. (No other previous JANUS experimgnc used unpainted or acetone painted groups of an;,nals.) A comparison of Figures 1 and 2 shows that there is no dif£erance between the mortality experience of the un-painted end aceCone-palnCed groups of Bg, and the same is true o£ BO, but there is a distinct dif£erence between the mortalities o£ the t~o experiments. Using Peto's logrank method (1) the two curves shown in Figure 1 were compared and found to be (s~acist£¢ally) significantly different from week 76 onwards. A slm£1ar comlmrison of the curves shcnwn in Figure 2 shows them to be signiflcantly different from week 52 onwards. Thus it is concluded thac the natural death rate (i.e. the death rate of uncreated animals) is sigulffcantly higher in experiment B9 than in experiment BO. This di£ference in death rates may be due to the £act Chat the ani=al 8uppl£er was changed between experiments B8 and Bg. For the series of expar~Jnents BO to B8 inclusive the an/~nl8 used were £emale albino mice of I.C.I. breed supplied by Animal Suppliers (London) Ltd. For experiment B9 Carvorth animals were used and were suppIied by Car~orth Europe. The circumstances Ieadin8 co this change of an£mal supplier are K£ven in (2), BAT Co LTD - MINNESOTA TOBACCO LITIGATION OD

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-8- 5. ANALYSTS OF CONDENSATE TREATED GROUPS B9-1 TO B9-6 5.1 Ana lysls of Znitial Death Rates AS mentioned previously, replacement animals were taken in to the experiment as a result of early deaths. These early deaths Kive some indication of the toxicity of the treatments used, and Table 33 shows the numbers of deaths in the 13 condensate treated groups during the first 20 weeks of the experiment. The dana for Bg-I to B9-6 are shown plotted in Figure 3, and inspection of this plot reveals no clear pattern of toxicity. Three of the six lines plotted have negative dose-response slopes, and the general pattern of crossed lines does not indicate any pronounced differences between the condensates. No analysis of variance of this data was carried out. 5.2 Analysis of Tumour Kates Uslng the Welbull distribution, c~mmon values of k and w, and separate values of b, were fitted to the data from the 12 groups of animals. A fit was obtained for all turnouts and for malignant turnouts only. The estimates of the parameters are shown in Tables 34 and 35. The associated values of S and V are shown in Tables 36 end 37. (S and V are the Weibull statistics and are defined at the foot of the tables. ) A goodness of fit test for these parameter values was carried out, the results being shown in Tables 38 and 39, and from these two tables it can be seen that the parameter values of Tables 34 and 35 provide an adequate fit to the data, neither value of X2 (12.24 for all turnouts and 12.57 for malignant turnouts, both with 6 dearees of freedom) being significant at the 95Z level of conf idence. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

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-9- The (natural) logarithms of the Weibull parameter b given in Tables 34 and 35 are shown plotted in Figures 4 and 5 respectively. Inspection of Figure & sugsests that the condensates may be ranked in the order B9-6, B9-5, B9-4, B9-2, B9-3, B9-1 of ascending tumorigenic activity. Table 40 shows an analysis of variance of these data, and Table 41 shows the tt~orisenic ratios of the condensaces obtained from this analysis. (For the method of analysis see (4).) From Table 40 it can be seen that the interaction effect between condensates and dose levels is not significant, indicating that the non-parallelism of she lines shown plotted in Figure & may be attributed to sampling error. Visual inspection of Figure & also suggests that there" are considerable differences between the condansates, and the highly significant condensate effect shown £n Table 41 confirms this. £f it is assumed that the lines shown plotted in Figure 4 are in fact parallel, then these between-condensate differences may be examined in more detail; the results are shown in Table 41. From this table of tumorigenic ratios and their 95Z confidence limits it can be seen that only the difference in activity between condensate B9-2 and B9-4 is not significant aS the 95Z confidence level; all the ocher between- condensate comparisons give a significant tumorigenic ratio. Tables 42 and 43 show the corresponding analysis of the mallgnant tumour data. From these tables, and Figure 5, ~t can be seen that the malignant tumour data analysis confirms the result of the all-tumour analysis. Fewer of the tumorigenic ratios are siEnlficant, but this is only to be expected since there are fewer animals bearing malignant tumours, but there are no contradictions in the sense that the malignant BAT Co LTD - MINNESOTA TOBACCO LITIGATION

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-10- tumour data did not produce a significant ratio when none was obtained for the all tumour data, and the ordering of the lines on the vertical f scale is the same in both figures (4 and 5). 5.3 Discussion o£ Results The initial death rates (deaths during the first 20 weeks o£ the exper~aent) revealed no dig£erances between condmnsatms Bg-1 to B9-6. Thus it may be inferred that there are no gross d£f£erences be~een the short-term toxicities o£ the condensates from these s~x materials in a mouse skin painting experLmant. The analysis o£ the tumour rates has sho~n some clear d££gerences between the condensates, and the major comparisons are as £ollows:- (a) extraction o£ the control blend leads to a reduction in the tumorigenicity of the condensate (Bg-1 v. B9-2). (b) the return o£ the extracted material to the extracted bland increases the tumo=igenic£ty og the condensate (B9-2 v. B9-3). (c) the increase in t,--~rigenlcity due to the adding back of the extracted material does not bring the activity back to the level of the control blend (Bg-L v. B9-3). (d) the tumor~enic activity o£ sheet mater~81 'A' is s£gui£icantly less than that o£ the control blend (Bg-L v. B9-4). (e) the tuaorizenic activity o£ sheet material 'B' is siL-ni£icantly less than that o£ both the control blend smd material 'A' (Bg-1 v. B9--5~ B9-4 v. B9-5). (£) the tumorigenic activity of sheet material 'C' is very low, and £s s£gni£icantly Less than that o£ the cont=ol blend (Bg-1 v. B9-6), material 'A' (B9-4 v. B9-6), and material 'B' (B9-5 v. B9-6). BAT Co LTD - MINNESOTA TOBACCO LITIGATION o',,

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-II- These results are based upon the analysis of the incidence of all tumour-bearing animals. The analysis of the incidence of animals bearing malignant tumours supports these conclusions when the numbers of animals bearing malignant tumours is sufficient to allow the comparlsous to be made. These results refer to the specific activity of the condensates from the six cigarettes. Reference to Table 4A shows that in general the deliveries of the test cigarettes were all lower than that of the control blend. The exception i8 for the cigarettes containing sheet material 'A' which had a higher delivery than the control blend. Thus on a per cigarette basis the appropriate ratio for Bg-I to B9-4 is 36 .254 x 2--~.5 - 0.345 ~rith an upper limit of about O.6. Thus the condensate from Bg-& clgarettes is still siKnLficantly less active than that from the control blend, even when allowance i8 made for the increased delivery of B9-4. e. LYS S OF cos zSsA. TUATE, ca0 ,, As noted an nhe beginning of ch£s report, nhis cigarette was included as a cross-check with an earlier JANUS exper/aent, B3. For completeness the data for the three condensate treated groups from experiment B3 are shown in Tables 45 to 51. 6.1 Analysis of Initial Death Rates Table 52 shows the numbers of deaths in these & condensate treated groups during the first 2Oweeks of treatment. These data are shown plotted in Figure 6 from whlch it is at once evident that the initial death rate in group B9-7 was much higher than in ~rperiment B3. ~t has already been noted that some of ~hese excess deaths ~ay be due no BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",,,a

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-12- the change of animal supplier, but inspactlon of Table 33 shows that the initial death rate in group B9-7 was considerably higher than that of any other condensate treated group in experiment B9, as well as being higher than the comparimon experiment B3. Thus it would seem that not a11 the excess deaths in B9-7 are due to the change of animal supplier, and that the storing of material B3 for experiment B9 could have resulted in a condensate of much higher toxicity. In this context it should also be noted (from Figures 1 and 2) chat although the overall death race of the B9 animals is higher than those of the previous supplier, during the first 20 weeks there is little or no difference, with a tendency for the B9 animals to have the lower mortallty. 6.2 Ana1~sis of Tumour Rates Using the Weibull distribution function, c~on values of k and w, and separate values of b, were fitted Vo the data from the 4 groups of animals. A fit was obta£ned for ali tumours and for malignant tumours only. The estimates of the par~ters are shown in Tables 53 and 54. The associated values of S and V are shown in Tables 55 and 56. A goodness-of-fit test for these parameters was carried out, the results beimg shown in Tables 57 and 58, and from these two cables it can be seen that the parameter values given in Tables 53 and 54 provide a good fit to the data, neither value of X2 (7.002 for all tumours and 2.711 for malignant tumours, both ~rith 6 degrees of freedom) being significant at the 95% level of confidence. Figures 7 and 8 show plots oE the (natural) loEarlthms of the Weibull parameter b versus the logarithm of the dose level. These plots also show the 95Z confidence regions for the values of logarithm b. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢,..m O',,

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-13- From these figures it is clear that although the tumorigenicity of ~he condensate used for group B9-7 is lower than would have been expected from experiment B3, it is non significantly so. Furthermore it must he remembered that the animal supplier was changed between these ~wo experiments, and ~t is therefore possible that the slightly reduced response of the animals in group B9-7 to what is nominally the same condensate as was used in experiment B3 may be due to this change, or due to storing the condensate, or both. 6.3 Discussion of Results The early mortality data suggests that condensate from the stored B3 material used in experiment B9 was more toxic than when originally made~ and the tumour dana indicate a sllghtly reduced tu~origenlcity in Bg. I~ is conceivable than the tumorigenicity of the condensate from the stored material and the condensate as originally prepared is the same, and that the slight reduction is due to the change of animals coupled with the higher toxicity. The techniques of analysis used attempt Co eliminate the effects o£ tumour~ess deaths as far as Ls possible, but it cannot be assumed that the procedurt is completely effective, and the higher death rate in B9-7 may have bed to a slight under-estimation of the Weibul~ parameter b. These results sugsast that long-term sto~aKe of the B3 cigarettes has had a greater affect on the (short-te~) toKic~ty than on the tumorigenicity of the condensate. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

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-14- REFERENCES 1. "Sequentlal Medical Trials", 2nd Edition, Ch. 7, P. Armitase, Blackwe11, 1975. 2. BioloBicsl Research Document No. 174/11o 3. "Long-term skin paintins experiments. General report on project JANUS". J. Kiendl, G. KSnigsmann, H. Kramer, Rmport B. 18, June 1970. "Mouse skin painting experiments. The collection of the data, and the analysis of the incidence of turnout-bearing animals". E.B. Wilkes, G.R. & D.C. Reporn (not yen issued), 1977. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

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-15- APPENDIX X The age-stamdardised eumour rates (all tumours) of JANUS experiment t B9 are:- Scandardised Group Dose Race (z) Bg-I 40 56.58 60 64.75 B9-2 40 30.73 60 38.86 B~-3 40 46.32 60 69.81 39-4 40 29.21 60 34.60 B9-5 40 12.30 60 25.58 B9-6 40 9.O3 60 6.46 B9-7 40 23.24 B3 25 11.66 50 49.07 75 60.45 Trans formed Rate 48.78 53.58 33.67 38.56 42.89 44.89 32.72 36.03 20.53 30.38 17 • 48 14.73 28.82 19.97 44.47 51.03 v For completeness, the B3 data are also shown. The transformation used is the arc sin square root. The Lee method of age standardisation was used. These data are shown plotted in Figures 9 and I0. Comparison of Figures 9 and I0 with Figures .4 and 7 shows that the ase-standardised data confirm the results o£ the Weibull analTs~s. Note that after age-standardlsation the data for 39-6 shows a negative dose/response. BAT Co LTD - MINNESOTA TOBACCO LITIGATION Q.p.r "-,,4 "--a

-16- APPENDIX TI The analyses of variance shown in Tables 40 and 41 were obtained f us£ng the £olloving design matrix:- Condensates Condensated x Doses Group ~ , " , d ~. ~ .... In Dose B9-1/40 1 0 0 0 0 0 0 0 0 0 0 0 3.68889 39-1/60 1 0 0 0 0 0 1 0 0 0 0 0 4.09435 B9-2/40 1 1 0 0 0 0 0 0 0 0 0 0 3.68889 B9-2/60 1 1 0 0 0 0 1 1 0 0 0 0 4.09435 39-3/40 1 0 1 0 0 0 0 0 0 0 0 0 3.68889 39-3/60 1 0 1 0 0 0 1 0 1 0 0 0 4.09435 39-4/60 1 0 0 1 0 O 0 O 0 O O O 3.68889 39-4/60 1 O O I O O I O 0 1 O O 4.09435 39-5/40 1 0 O O 1 0 O O 0 0 O O 3.68889 39-5/601 1 O O O 1 O i O 0 0 1 O 4.09435 39-6/40 1 O O O 0 1 0 O 0 O O O 3.68889 B9-6/60 1 0 0 0 0 I 1 0 0 0 O 1 1 4.09435 I and the hypothesis vectors were:- ~I~I I I ..... IIII I I I I MEAN MEAN + CONDENSATES Io Ioloi ° I° I~ I~ I I I I I ~AN ÷ DOSE MEAN + CONDENSATES + DOSE (TUMOUR EATXOS) FULL MODEL 1 I I I I BAT Co LTD - MINNESOTA TOBACCO LITIGATION C.J1

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-17- APPENDIX III The analyses of vazlance of the tumour races of Stoups B9-1 co B9-6 is shown in Tables 40 and 41. These six ciEarettes were manufactured as follows:- 39-1:- Control flue-cured blend manufactured in the usual way. Lamina to CES ratio was 60:40. Lamina cut at 56 c.p.i, and stem run at 180 c.p.i. B9-2:- As Bg-I, hut the tobacco was extracted v~th ethanol prior to cigarette manufacture. B9-3:- As B9-1, but the tobacco was extracted with ethanol and the extracted material returned to the tobacco prior to cigarette manufacture. 39-4:- The control blend was manufactured into PCL by Z.T.P. in Montreal. The ratio of "dry" slde=material to binder was again 3:1, but the lamina blend only was used for the "dry" side. In addition swlditives believed to be similar to those used by Gerlach, including 0.37 parrs of E17cerol, were incorporated so that 4.94 parts were processed in PCL. 39-5:- Sheet material made by Gerlach from the tobacco used for Bg-I. B9-6:- Sheet material made by Gerlach from the tobacco used for B9-2. The analysis leads to the following conclusions:- (a) ethanol extraction of flue-cured tobacco s~sn£ficantly reduces the tumorigenicity of the condensate (B9-1 versus B9-2). (h) return of the ethanol extracted material to the extracted tobacco increases the cumoriEeniclty of the condensate (B9-2 versus B9-3) but the increase does not brine the tumorigenic activity back to the level of the original blend (B9-1 versus B9-3). BAT Co LTD - MINNESOTA TOBACCO LITIGATION "-.,,j --..j

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-18- (c) the tumorigenicity of the condensate £rc~ the PCL w~th "Gerlach" additives (prepared from the control blend) is si~ificantly lower than ! that of the control blend (B9-1 versus B9-4). (d) the activity of the condensate £romCerlach sheet is significantly lower than that of the control bleed (B9-1 versus B9-5). It £s also significantly lower than that of the condensate from PCL with Gerlach additives (B9-4 versus B9-5). (e) the tumorisenic activity of the condensate from Gezlach sheet manufactured from ethanol extracted tobacco ~s very low, and it has been noted that this material, B9-6, gave rise to no malignant tumours. Also, the results suggest that the ef£ects due to Gerlach sheet manufacture and ethanol extraction are additive. The effect of ethanol is to reduce the activity of the original blend by a factor of 0.320 i.e. the activity of condensate B9-2 is 0.320 times as active as the activity of the condensate from Bg-1. Similarly the effect due to the Gerlach method of manu£acture is to reduce the activity by a factor of 0.142 (ratio of Bg-1 to B9-5). Thus we miKht expect the combination o£ both process to reduce the activity by a £actor of 0.320 x O.l&Z - 0.045, which agrees extremely well with the observed factor of 0.051 (tun~rigenic ratio Bg-1 to B9-6). These conclusions are drawn from the analysis o£ the incidence of all cumour-bearing animals. The analysis of the incidence o£ malignant tumour-bearing animals supports these conclusions when the numbers of animals bearing a maliKuant t~nour is large enough to allow the necessary comparisons to be made. BAT Co LTD - MINN~TA TOBACCO LITIGATION C

,.-1 N @ t'- ..-j t~ I +.....+ Z Z © t~ c~ © t" -.] © Z .j C R-l,f, COo R,nHo 0,0, ImOJ(Clr jINUS IqClO[NCl[ OIr H[v TU~OS~-D[JRINO AN/HII.S ~xP~aZHFHT OqPO qO| [XPT Oe UHTmF.JV~ ¢OHTROL T|N[ ILL TU~OuPS ffnlO0 N 0! 02 R(PORT -19- HIL i~Mulf YI~*OWS N Oi 02 I- * 148 0 I 14P e I S- A 14T 0 O I*? i e 9- 12 142 0 e I*T | e 13- 16 147 | O I4T 0 | 17- 20 142 0 ! 14? 0 I 21- 24 146 0 I 16~ O I 2So 2q 145 0 i 16~ 0 I 29° 32 144 O | 146 $ | $3- 36 ]43 0 0 143 0 0 31- •0 |43 0 S 1•3 I § • l- •• i3A 0 • 13~ t • 4q- 4A 134 0 | 12~ 0 I 44- SZs 133 0 2 133 e 2 H3- 56 131 0 • 13! 0 4 5?* 60 122 0 5 121 0 S 61- 64 122 0 • 122 0 4 6S- 6n It! 0 tO I10 l II 64- 72 lOS 0 6 IOA | 6 23- 76 Io2 0 lO le2 e I~ 72- ne q4 0 10 R• 0 1O il- i4 94 O 12 76 t l| aq- 02 S5 0 8 s5 O n q)- ~ 4? 0, IO •1 e le e?olO4 32 0 S 3? O S lel-lO4 32 0 IS 2? e IS le~-leO 17 o I I1 0 ] 1;9-112 16 0 7 14 l 7 ll3-ll~ e 0 • q o 4 Ill-lie 5 0 e s t e 1~1o124 S 0 • S | 6 lfS-IH l 0 l l e e I++-13z I e I I + l ?6/oeli3. PACE ] Pt'PNI~HTLy +[Oa(S5[0 L[SIOH50.ltf[O PEPLICrm~M? ANIMALS IH~LtI+r+ 08 Iz 1/cJo I YOTIL O 168 e lip q • MO. Olr IHIMILS IT RISK IT TH[ KG|HIIII~ 01" 114[ Tit[ PtRIOO h| • N~. or IHlUALS D[COMINfi TUNIOUIII-P[IR|HIO f)UPlN(t TH£ Yl~+ P[UlOO 02 • NO. Of" aMIVILS 0YlMfi ~+fmO THF TTHI[ P[nlt'~ HITH~IT q£COHING TL~Ot!R*PPJqII, IG TIM[ PP;t+OS ARt oIr FOUR V[[V+ OUgaTION

-..I N o L"" -..I ! Z Z -.] © $ [..-. -.] i ~> -.] © Z -20- TAELZ 2 R*A,T, CO, P,AND O.D, PROJECT JANUS It[PORT ROSO| I~lOE.qC[ OF N(V TUPJo~-q[.IqlNG aNIMaLS (xPT 119 JC~TON( TI~ATEID C09~PiOL [XI~.R|P[NT BqI 902 TI~E M..L T~4~S PEPIOO N Ol D2 ~*LT~AHT Tu~mmS N DI O? 1- 4 168 O I 141 t. | S* 8 161 0 0 147 | I 9- 12 16T O 0 i*? 0 ,0 1]- |6 16T O I 16T 4 | 17" 20 1~6 O i I~ 0 I 21- 2& 16S O ! 16S O I 75- 28 166 O 2 . 164 O 2 2q- 32 I*! O Z 16Z O 2 33- 36 160 I Z ItI O 2 37- *0 lie I I 13n 0 I 41- 66 137 t 5 131 O 5 65- 4~ I32 0 ~ 13~ 0 6q* S? J3O 0 & J30 0 6 5~- S~ 126 O 3 126 0 3 ~7- 60 123 t 4 123 0 6 61- 64 lie O 3 IIq I 3 65- 60 ||6 O S 116 0 S 6q- ?Z Ill I 12 I11 O 12 T~- 76 9q 0 IO 9g O JO ?T- |O Be 0 | Iq 0 8 81- 06 01 0 e Pl O 8~- |q 12 I T T2 O T M- q2 6S . O |t &S I 11 O)* 96 S4 O , 9 r~ 0 q qYoleO 6S I 13 *S O 13 IOl-le* 32 I 3 32 O 3 lOS-lee 29 O y z9 O T IOq*li2 22 O 3 ?~ 0 3 It3-ll6 19 o 9 Iq I q III-IZO 19 0 S lo e 1~10124 ! I I S 0 I 12S-lie 6 I 2 6 e J2q-J3? ~ O O 2 0 0 131-13& | I O 2 O I I)?-I*O l O 0 2 O 0 i4t-|44 2 | I 2 0 1 I~S*16O I O 0 I I 0 IIO-IS2 I O I I 0 I ( T6IOO/13. PIG[ PEnNANE"NTLY W[GRESS[O LESIOHS OHtTTEO flEPLAC[PFNT iNIaALS |NCLLff)Ffl 18 I /.ciI ,c 01 TOTAL I 168 I ImP N • NO, OF JNINIL5 iT RISK iT TH( n(OlqUl~S or THe. TTXE P(l~fO0 Ol • NO, OF iN|PILS ~(¢OPl~fi Tt./o4OUII-R(IPIa~ IHJ~TNG T~:. T|P~ P~P|OO ~ = H~, C~r IN|.i~$ OY|H(I ~I:INH'~ I1~ T|H[ P(PlOD v|TI41QUT fl(COHfHfi TUuOUI?-RESRTNG TIME PEDRO,S X~ OF FOU~ NETKS OIIPAV|ON

N @ | Z Z -..] © © Z O-A,T, CO. AoMNO O,O, PIqOJ[CT JaHUS INCIOt'NC[ Or N[Id TU~OU~-fI[ANING &ulMJt'LS [xptrPlMEMT 091 e&o [XPT SliP/! CONTROL 60M0 ILL TIP--S N OI I)Z I~POItT TABLE 3 mo~41 NIL TI~NANT TtllaOUe$ N O! O? l- 4 Ire e 1 Ill 0 1 S° 8 161 O ! 147 0 I 9- 12 166 o e I4~ e e 130 16 146 4 I It& o ' I I?- 2o llS 4 I ItS 0 l 21- 24 164 4 3 It4 I $ 2S- Zl 161 4 O 161 O O 200 32 Ill I O I*l O e 33- 36 IQO I 1 161 O. I 3~- 6e 139 I I 16o o I 61- 66 131 I | J3q o I 4s0 to 13S ~ I 138 O I 6e- 52 132 S | 137 t 2 63- 54 126 6 S I3S I 7 S?- tt I11 1 3 127 0 6 61- 6* lOl 6 S IZ3 0 6 6S* 60 96 3 9 lit O l0 6~- 72 06 6 3 10? I ? 73- 74 75 7 5 100 I 77° 04 62 3 S 91 3 6 81- 04 S6 Z 4 O? S 9 OS- 0| 64 3 6 66 2 A 0q- e2 3~. 6 le so o 14 Q3- ~, Zs 2. ~ 64 I a qT*lie 21 3 3 3~ I 141-106 IS 0 3 2A 2 5 lOS-Ill 12 2 4 20 3 4 leO*It2 5 I I 13 t l 1130115 6 1 2 13 2 3 1170124 3 i i I 0 6 1210124 I 0 O 4 I I 12~-12a I O I 2 O I I~qol3~ I o i 76/00t13, PaG( PEPHtNENTLY R~OACSS(O LES|OHS O;4ITTEO n(PLJC[HTNT ANIHAL$ IHfI.U~O 15 • w TOTAL. 64 84 22 126 N • NO, Of INIHJLS iT RISK t? TH( I~OlNNI~i~ OP ?tq[ YlHf PTRlOfl 0J • NO, Of IHI~ALS n(C0~tN~ ?tPJOL~on[t~/NG OU~TNG Tt,I~ fl~ PfOfO0 p~ • ~, Of AHIN~LS OYIH~ OtNI"G.. I14[ ?IMF P~AiO0 VTTHOUT RECOilS5 TUIIOb'~*PfAAIN6 TIq[ P[~f0n5 A~[ OF" f0UR Vfr~S filtRATION

N o I Z Z © N © © Z .. C t~-t.T. CO,, II.6NO ID.D. PIIO,,I[¢T JANUS ItlCll)l~H('[ or 14115 ~I)-FI[IJIIN6 Iml#ALS ~xPFQIq[WT Oel O~e [XPT !141/I CONlnOI. 6eHG Tim( iLL TUI4OUnS P[nlO0 N O! 02 nL,~l+l' -22- TARI,[ 4 1tl)501 HAL |I'INIlIT TIINOUIIS 14 01 07. I~ 4 l+e 0 I I~0 l I s- I If? 0 l 1+7 o 0 e- 1~ i~I e o 147 e .e 13- 16 I57 0 0 167 e l I?= II I*? o I 14y l + +Io ++ l+S | 1 145 o I Z5* ZO I+* O O 14* I O Z~- 3Z 164 I 1 146 l l 33- 36 !*+ ! + 14~ l 37- 60 139 Z S I+I e S 61- 44 132 6 1 136 O I 450 48 125 • 6 135 e + 45- 52 ii5 + 3 12e I 5]-54| IOl II 5 125 I 6 57- II 9| Jb 3 117 l 6 +I- l+ 7S 9 3 I12 I + 6S- 6q 13 S 6 lOT l q &q* 72 52 & 4 9R 2 8 73- 76 6~ • 5 OR l R 77- 81 35 I 2 80 S 6 81* 04 3~ 3 4 6q 4 7 .no. on 2~ 3 2 Sn 2 +l- 95 20. Z 7 52 Z II q~- q4 II I I 3g 2 9 QT*IOI l e 3 28 O 8 101-104 6 I Z 20 2 3 I05-I08 3 e I IS I + l+~-llt ! o + It l 2 11]-116 T 3 I II?-l~O ] I e 121-124 2 I o 125-1~8 I e I 78/08113. PiG[ P[AH&NEHTLY RFGIt[SS[D L[510t15 OMI?I[O PEPLAC[~[HT ANIHIL$ 114CLUIOtA ?3 70YJL 16 72 31 117 N • NO. OF AHI.ILS It +fSK l! 711t[ qrOll+llt~ or 7Ht Tlq[ P[nlOfl Oi • IE), O~ +HImALS ~[t0~ll~ TUI~0U~-~[+RINO 0UPING TH[ Tlm~ P[~lOfl D? • IC. @P +fll.IL+ OYll~ ~*P114G TH~ Tim[ P[nlo~ vlIHOUT +~CO~Imn IUIaOU~-Bf~INO Tlmr p(~lfl~ ll~" of r~l+ N[FxS I'jIJR&TIOH

.-] o t" I Z Z > O > n 0 n > 0 Z C P-&.To CO. P,AHD O.O. Pll0J(CT JANUS II¢lO[MCr. Of' 14LrV TUIqOU~-R[AfI|fl6 ANIHIOLS [XPc.PItqENIT 092 i4e [XPT B9/2 [XTPACTleO TOB&CCO 48146 TIP£ KL VlPPOI;oS P(Ol00 x OI 02 I- 4 14q ! ! ~0 8 16; o i q- 12 146 I o 13- 16 146 | 2 17- ~o 144 t o ~I- i~ 144 0 e 25- 26 1~6 0 O 2q- 32 144 O O 31- 36 146 I I 37- mO 143 l t 41- 44 139 3 I 65* 40 13S t I 40- 52 1~5 I S 51-56 129 2 3 Sy- 60 |~4 ] 4 61- 64 111 3 ? 5~- in III i T &9* 72 llO 3 9 71- T6 8q 3 6 77- 80 79 2 8 PI- 84 69 l 9 n~. 88 s9 3 II nq- 92 *S, I 6 91- ')6 38 2 . 4 97-J00 32 I 9 I010104 12 I s IOS-lOa 16 I ] lOq-ll+ 12 I | |13-116 6 0 IIT-120 6 0 I 121-114 3 I l 185-128 3 O + 12o-132 I O l 133-136 I 0 1 13T*140 alL~ORT ROSOI -23- TABLE 5 NALIONmqT TUIqOUP'S OI 02 I~4 O ? 14"/ 4 | 146 o II 1',6 0 2 144 I O 146 l O 16& 0 O 144 0 O 146 0 • O l+.r, 0 6 140 o I 13c) 0 o lY* t S 13. O :3 131 I 4 126 I 8 lln l 8 IiO ii II qq) 0 P ql I ml II IS 71 0 12 S9 I Y St 0 7 4~ 0 13 31 0 9 72 0 § 17 l • q 0 + O 3 0 I IS 1 . 7~t0n/12. PlGT P[PHIH[HTLY ItYflRES5~O L[SIONS OHITT[O R~PLICFPq[HT &H|H&LS INCLUDED 33 ; • TOTIL 3t tit 6 14S N • NO. Otr iNlUlLS IT ~lS[ if T~[ ~[GIt~ING Or TH[ TlX[ I~PlOfl OI • ~, o~" aNimaLS fl~CO~lNn TIINOU~-NEININfl lY, JRTNG TVE TTNF. PEP|OO p~ • NO. OF ANIUA~S OYING 9UO|NG TH( T|M[ PEP|Off M|THOUT PECONINO TU*qOU~-~FI~IN6 flue PEqI00S IR[ OF FOUR HEF~S ~lPiT|flrl

-.] N o ! Z Z © © t...,. © Z ( w -2~- N[POnT NO501 TADI,E 6 8*i,T, CO. ~,tND 0,9, PHO./ECT JANUS INC/D[NCf OF *~v TUNOUnoO~aNING ANIMALS fXPENI.~rNT 092 060 [XPT IPll2 (XTPACT[O TOOiCCO 60fig TIMe ALL TUNOI~S WAL|~NAHT TUNOUP~ p(nlOO N OI 02 N OI 02 I- 4 140 O l 14n O I S* O 142 O 0 14T 0 0 9- 12 147 0 | 147 0 0 13- 16 147 0 I 142 0 I I1- to 146 o o 146 o o ZIo Z4 146 O i 144 0 I 2q* Z8 14S O 0 146 I o ~q- ]2 145 e 2 14S 0 ? 33o 36 143 O 3 143 O 3 3T- *0 144 2 3 140 0 ) 41o 44 135 I I 137 0 I 4~o 4n 133 O I lib ! I 4e- $2 - 132 t I 135 0 I $3o 5~ 12q 2 Z 134 0 2 57+ 60 1~5 4 4 13? 0 S 61- aS lit S I IZ? I a ~- 60 JJ5 ~ ' T lie J p ~q- ?~ 96 ~ 9 111 o to 23- 76 l~ 4 II I01 l l? 71- I0 ?0 S 4 OR I S ql- 84 61 ~ T 82 e q q~- On 5Z Z $ T3 ! tO 8q* q~ 42. 3 6 63 I P q~- q6 33 I , 4 64 ? qT-IO0 2A | 6 47 O II 10l*104 22 O 8 3~ ? IP JOS-J|~ J4 | 3 2? I A lqQ-ll~ le I 4 IS l 7 113-116 g 1 | y O O liT-120 4 o I • I 1 121-126 3 O 2 s I 3 IFq-12n I | 0 I • 0 0 12a-132 l O 0 I 0 1~I-140 I 0 i ! 0 I ( P£~MAH(NTLY P[Off~SSEO LESION~ OP'|TT(~ R[PLAC(M~NT ANIMALS INCLI~[O 41 TOTAL 40 iOa 10 13n N • NO, Of AHIqALS AT ~IS~ iT TH~ n[Gl.NNIN6 OF T0~. TIU~ P[PlO~ PI • NO. Of ANIMALS 8[CO'~IN~ TL~OUR-fl(A~INNt OUHIING TN[ TIU[ P[PlOI'~ O? • NO. OF ANIMALS OYIN~ OllOiqG INT. TIN( PEqlOO M[THOUT P[C(mfN~ TUIq(1LIgoprlRING ylur P[n|OOS ~PE OF FOUo ME£KS DUPATION

> ,..-I 0 t" .....] I Z Z +_+ > ..-] © © r-' t.-,,q -..+ > --+ © Z -25- TABLE 7 q-A.T. CO. PoAHO 0.00 PII4OJ(CT JANUS R[PORT ITD5411 PlCln(~( OF td[ll ?I.mlOQII-PEMIIHO Im|Mil.S fXPF~INENT 893 040 [XPT 84/] [XTaACT(O mETU~N~D tOI4O TlflY ALL TUWlUgS PrnlO0 N Ol O2 !- t lit i e So q I~Y O O q- 12 167 O 0 13° 16 |67 | | I?- ~e . 1.6 e Z ~1- ~* 144 O 0 2So Z| 164 | ~qo 3E 1.8 O I ~3- 3b |~J O i 37- ,e I** + 4 41- ,4 13Z l I is- 4+ 130 S i 4q- S2 • 124 O I S~* $6 123 I S S7- 61 i1? S O 610 66 llZ I 6 6q- 60 llS ~ 6 6q- 72 qq O T~- 16 8S * S TT- ~O T6 ~ O hi- A~ 66 s o a~- OQ S] 3 9 Ao* 9Z 4l 6 ? 9~* q~ 30 I. 7 9T-lOl 2Z Z T I01-I0~ 13 ] I lOq-l++ + l t IOq-ll+ ? I I II+-II+ 6 I I I11-121 5 I + IZl-1+4 I I t 125-121 I t l 12e-137 I I I 141LIGI41MT TlJl4OUOS 01 O2 161' 4 0 1++1 41 0 1+17 0 O I~V 41 ' I 14+6 o 2 I++++ 0 0 164+ 41 ~ . 16~? 41 I I*1 II. I 1++41 41 4 136 41 I I..15 41 I I)4 41 I 153 41 S IZJl 0 I 127 41 A IIq t 8 lit l 106 41 6 Ill 41 I0 ,Pit ~ I I 7T I II 6S q IO SO 3 n $9 n 12 ZT I 4 ZP. 2 S 15 3 ] 9 2 ! 41 4 41 41 41 0 41 2 ( T6/Om/13. PAG( PEqUiN[NTLY ~fl,T$SE9 L(SIO~S Ol+lIT[~ P[PLIC[H[N| IN|MILS IHCUII~9 49 981+/_G,1 01 TOTAL S) 9++ 20 127 N • NO. Or INIHIL5 it ~ISI( at THI~ ,[el~tmo or V~" Vl.~ P[BIO~ Ol • NO, OF ANIq&L5 8(¢OulNfi YU~OU~-8(IPING DU~TqI~ Tx[ TIM( PFPl04 O? • NIl, @P lulmILS OYl,qG ~IMO T~( tl+( Pt+lOq Vat.OUT ~(CPx|mfi ?UPlOLIm-RtI~IXG T|v( prolog~ APP OF Fc)UQ vfrms I)UPiTI{~

. ( ( _ N o I K Z Z > O > N 0 > 0 Z I-A.Y. CO. lie.AND P.O- PI~JI[CT JANUS I~(POI~T itOSOI INClD(I~[ 0t" ~ I~*OUm-*~tAAINO ltilill.S [XPFPIM[NT Oq) 060 [XPT B9/3 EXT~ACT(D A(TUPN(9 60NG ALL TI~OUA~ k O! 02 -26- TABLE 8 NtL|GNANT TUMOUPS H O| O? I- 6 |iT I | 1iT I e ~- R 16T I I 16Y I I q- 12 161 ! 0 ItY O t !1- 16 |4T O 0 161 I I I1- 20 141 I O 1~1 t o 21- 26 161 I 2 I&? O 2 2~* 28 I~S I O . 165 O o 29- 32 145 I ! !~S I I 33- 36 143 t 3 144 I 3 32- ,e l*e e ~ 141 o 41- 4~ 131 3 2 132 e 2 65- 40 126 6 2 130 0 ? • q* S~ IZO 3 3 12~ t 3 s)- $6 114 ] s 12S O ~10 60 IN S ) 128 i 61- 64 9A ~ s 116 l 6 6S- 61 90 4 S IOe i ? 69- 72 II 6 6 102 0 S 71- 76 73 i II 91 I 12 72- 80 56 O O 86 I q 81- 86 40 4 6 IS 2 P AS- 8~ 30 ~ 6 6S 3 8 riG- 92 3e 1 3 s, 6 s q3- 9~ 26 I . 6 4S 3 6 92-100 |1 O 2 3~ i S 10l-lO6 |q 3 6 31. 2 ? IO~-IOA I0 t ~ |P ! leg-Ill I ! 3 14 I 6 113-116 4 I i Y 2 I IIT*IZO 3 I I A I I 1210126 1 I 0 3 I I 125-12R 1 I 1 ) o 1 76/08t13. PIG[ q? PTn~AI~HTLY ~[fiq[ss[D L(glOH~ r~ITTT[D ~[PLAC[M[N~ ANIHALS |I~LUO(O .Y TOYAL 49 98 22 12~ q . 140. OF INl~iLS AT PlS¢ iT TH[ ~[61NNII~ Or 114~ Yl~r P[Pln~ OI • NO, OF iNJtiLS ~(COPIN~ TI~OU~-P[APlHG ouq|NG TI~ fT*4~ P~PIOD D2 - NO. Or ANlUlLS OYIHG OlJOlNG IOW TIH~ P(PiOO VlTHOI.JT pECO"IN~ TUY4Ord~-OFIRIX~ TI~[ P(~|OPS IP~ OF FOU~ VE~.S ~Un~T|OH

.-] o t-" ..-I I ~Z TZ O O ,-.] O O Z -27- TABLE 9 II-A,T, CO. Roam O.O, PIIOJtCT JANUS t ll4CIO[qc[ Of N[II TUNOUII*q~IUlIN~, AHllIaL.q [Xp[u|i[HT 094 I)40 Ri[PO~T ROSOI [XPT !19/4 III[CONST|TUI'[O 5HE[T ~ 40141 TIN[ aLL TUqOUmS ~P lOb # O I 02 I- 4 14T e $ q* IE 166 I e |3- 15 146 | I IT- ZO J&S I f 21- t~ 16S O i 2Q- 3Z 164 | O 31- 36143 O i 3T- *0I*Z l 6 ~l- m4135 i O a~- mOi3q Z 4 SO- 52 - 129 2 2 $3- 56IZS i I ST- 6O123 O 6 61- 04J]9 3 8 6S- 6tIO| O I 65- 7ZtO? ~ O tS- ~6qT S 3 T?- oOit t 9 ~l* O*~0 I 13 q~- $~66 O 13 0*- 9~53. 3 IO 9~- 956| Z, 3 QT-IOO 35 1 !01-104 ZS D 6 IO~-IOe 19 O toe-II~ By I , ll1-lll l~ t 3 IIT*i~O ? I o 121-1ft T I 6 IZS-12~ 1 0 t 1~-13~ I 0 I 13~0135 N&LleINaHT TUMOU~ nl D? I¢? O O 14T 0 I 166 O P 1~6 0 " I I*~ O O 14S 0 I 16. O 0 |&& O O 14& n, I 1~3 0 6 13T o 0 I)/ o • 13~ 0 2 131 o ? IZ~ I & I~ 0 n 116 0 P 116 0 II le, e 3 Ill O e 92 O l~ ~n ~ 16 6~ I I~ IT O 6 41 0 tO 31 e 5 Z6 o L IS t • q 0 0 ! O I 76/0~/13, FAG[ P[RMAIq[NTLY N~C~[SS[O L[SION50MITT[O R[PLAC[NYHT ANIHALS |NCLUD[9 6S TOTAL 29 lip n 139 x • H0. 0~" ANINILS it RiSK at Vl~ 8[6IHNTNG Of" THE TlU~ P[PI00 DI • NO. Of ANi,aIL~ eE¢Ou/Xfi I"VNOUP-PfInING OILING TXE Tl~E PEn/O0 ~ • PJO. Of ANIuILS OYIHfi DI~IHG V~r fief P[PIOO V|TI40IIT qrcoi|~ TU~OUP-O~ARING llX( PEP|ODS al~r ~F FOUP kF~RK OUR&T|~M

t3~ > N O r- -+ ! Z Z > O ~33 > O -q 0 > 0 Z -28- TABLE 10 n-A.T, COo RoANO O,0, PROJ(CT JINU$ INCIO(I~[ Or N[W tUHflUAoP(AP|H6 AHINALS [XP£QItAENT 09~ 060 [XPT 89/4 RECON~T|TUT[D SHTET A 60140 TIN[ ALL TU~0URS P[nI0O N 01 fie !" ~ IS! I S S* 8 16T I 0 9" 12 lit O 0 l~- 16 ILT I | It- ~0 I~6 I I Zl- 14 I~6 I 0 2~- 88 166 I | ~Q- 32 1~6 O I 31- 36 144 ! I 3t- 60 1~2 I * 41- .4 |3~ O 2 4~- *R 136 l I • q- S~ 134 l 2 $3- S~ 131 l 6 $?° 6o 120 I 6 61° 64 |14 2 4 6~* 6~ 118 ~ 8 eq- 72 qA I 4 71- Rfl 8~ I 9 8~- 8R sq 3 t ~q- q2 As I t q30 96 41 0 , S qt*l|l 36 6 S 1M-lOt ~ 0 lO I15-10~ 15 0 4 Inq-Ill !i 3 11~-116 6 0 3 II?-I~I 3 0 e I~I-IE~ 3 0 I I~-I~ ~ 0 I 12q*132 I o o 113-136 I o I I~PORT nO, hi H6L IGNANT TU~0URq N OI 02 I~? 16t 14~ 146 139 13t 136 134 12t 120 JJ6 lOP I0~ qt Ot 76 AS SO 40 ~6 EO 16 45 el 3 2 O .q 0 (I P 0 O '1 e o o o o o o o • I O 6 0 0 I 0 ? 0 7 e 0 II II 4 I I q I IZ 0 q I 7 S I q ! 13 t .q I 3 1 7 0 ! I I • I I I e 41 ~? T610P/13. PiG[ PEnMAH[NTLY P[~R~S5~O L~$IOI~IS OUlTT[O P[PLaC[H['HT AHIHALS |HCLUO[O t~ tOtaL 34 I|l I* 13~ N - NO. OF INl~iL! At RVS~ It TP( qE61NNIq~ OF T~r TlW~ P[RI0~ DI • Nil, Or AHIVALS R(C0mltl~ TU~0UR-n[IR|Nfl 0UP|NG TIE TIfF P[Ptfl9 D? • HO. Or AH|mALS OYJHfi ~m|N6 t'r tl'[ PE~lOID ~ITHOUT RECOHI~G TUNOI~-P~ARING Tt~r P~JOn5 inF OF' FOUR W[F~5 ~URATTOq

N o t-' -] I K z z .-] © C~ $ t -] .-m C~ > --] © Z C -29- TABLE It P-~oT. CO. me/NO O°0. PROJT, CT JANUS REPORT ROSel l~In(N~( or NTv T~4OUn-n~AnlN6 aHInSL5 /xpfn|HFqT 09'5 e,t EKPT goIS RECONqT|TUT(O SHE(T R &0~6 11~r ~LL TUMI1Uff~ NILI(~NANT TUUOUII~ PEn|OR N Ol DZ N OI D? |- t 147 t o 167 o Q S- ~ lit | 1 147 0 I Q- 12 166 0 0 14~ O ,I J3- 16 |26 0 0 |4~ 0 0 IT- Z0 146 0 0 14~ 0 e 210 54 166 0 2 J66 ~ 2 25- Zq 164 0 ! 146 ~ ] 2q- 32 143 0 0 143 O 0 33- 36 143 0 3 143 fl • 3 ~?- ~o I40 0 3 14o 0 41- 44- 132 0 | I~T 0 | 45- 6~ 136 0 I 13^ 0 I • Q- SZ 13~ 0 2 13~ 0 2 53- 56 133 I T 133 0 Y ST- 60 I2S ~ 4 |26 0 4 61- 6~ - 119 I 3 IP? 0 3 ~- 6A IIS I "9 lie 0 9 69- 12 106 | $ IIO 0 5 T1- T~ I0! I O iO~ I yl- N g2 I 4 46 O 6 el- 8~ 8s 3 II qP o II n~- on T6 2 12 nl 0 12 no- g2 60 I T 6q 0 # ~1- 96 52 0 . T 61 I g 9T-J00 4S 0 13 $1 o 14 lel-IOt 32 I T 37. I O IO~-|lq 24 I 6 Z~ o 6 ltO-ll~ I$ t 6 ~ 0 10 111-116 13 0 4 14 0 • liT-120 R O 2 II O 2 12~-12~ S I Z s 0 ) 17e°132 3 | I ) 0 I 133013~ ? 0 O 2 0 0 l)?-I~O Z 0 I 2 0 I I~l-iki I I O I 0 0 J4q-|k~ J O 1 | 0 ! C .m 7~/08tl3. PaGE PEP~a~/~'HTLY aEG~S$~fl L~SIONS OUITT~D ~EPLiCEKIPNT AN~iL~ |NC~UDED 06PL ;I;, O I TOTAL 13 13~ 3 1¢~ X - NO. OF iNI,AL$ iT RISK IT TH( BEOI~IX~ Of' Yx~ YlUT P~IOD 91 s NO. Oft. ~NI~iLS ~(COMIHfl TU~H~oP(ERINO BUssING ~ME T~u~ PEP|00 ~? = N~. OF CNI~aLS ~Y|Nfi ~iO|NG T~ TIV~ PEUlO0 VIT~O~IT urC~4l~lG IUX~Uq-Bfi~ING TIv~ PFOl¢10~ iPr Or FOUA VFF~S flL~ATION

> 0 I Z Z ~n > 0 > 0 ,-+ 0 Z -30- TABLE 12 O-I.T, CO, R,P~ O,O, PROJECT JINUS |NC|n£NC~OirNf~ TUMQt/R-n(/PI|HG INIHILS (XPrOI~(MT 0~ 060 (XPT 9qt$ R~CO~STITUT[O StNIIE[T R 6OVG lINE iLL TU~IfI~ P(RIOD N fll 02 I- t 151 0 ~- A Itn t O q- IZ 14~ 0 I 13- I~ !17 O I 17- ~1 141 O I 21- 21 141 I I Z5- Zt 141 I t 29- 3~ 161 0 ! 31- 36 146 I 3 37- 4t 14~ O IO 41- 44. 13~ I 3 6~- 6n 12~ I ! 6q- $~ IZl 2 2 63- $6 If3 I ! $1- ~l Ili Z 6 ~1- 1,4 113 I $ 6q- 6l 109 I II 6q- 72 ql 0 12 T~* I~ 85 2 !! T7- OI 72 | T hi- S4 ~ 2 4 0~- 8q Se 2 7 nq- 92 ~9. 2 • 93- 96 3D 2 . Z ~¥-IOl 34 I T Ill*ill z5 I ? IO~-IOO I1 I 3 l~q-ll2 13 O n lI~-ll6 5 I I ll1-lTt • l i 121-124 3 t I~POItT N05ol MILI~N~T TI~Ot~S Ol O? IS? I q 16n O 0 t6n 0 I 167 0 "l 147 0 I 147 O 0 117 O 0 I~9 O I 14~ n • 3 143 O I0 133 0 3 130 I I 12q o 2 127 I 3 126 O i I~I I il7 I II 105 l I? 91 0 I? fll 0 7 T4 0 10 I 7 6P 2 I? 46 O 36 O I~ 26 O S le o Io o 3 C ?610D/13. PAGE PEPMINENTLY P(e~ESS[O LESIONS O~lYTfO P[PL&C[Ht:.HT PHIHALS IflCLUO~O AT 16P/gP 01 TOTiL ~5 13Z S IS~ a - MO. Or INliiLS tT RIS, iT TI+( O[PlHNIHO Of" T~ TIM( P[~lO~ Pl - NO. Of INlqtLS ~[¢OM|N~ TQ~4OUA-I£APlH~ DU~IHG ?H( TIM[ P[PIOO ~? • HO. Of XN|aPLK DYING Pigtail lH~ TIM[ PPoIO0 wt?~mot PECO~luG T~UP-ArIQ|tI~ t!ur PEAIO~ ~or OF rWJO H~¢kS ~)DITIIII,,I

o p- I Z Z .-+ 3~ 0 > 0 w-q 0 3) 0 Z C P-A.T, CO, A,AgO 8,1). PIIOJECT JANUS INCIDEHCf OF HEll TUMflUP-A(AAING AN/UeLS FXPIP~I|u(NT 0q6 14t F.XPT 89/6 A[CON.~T|TUT[O SHE[T C 40~G TImE ILL TUmOUn~ PEPlOD ~ D! 02 1- 4 ItR | I ~ A 14? I O q- 12 141 I O t3* 14 I~1 e Q I?- 21 147 | 3 21- 24 144 t o 2~- 2n 184 I l 2q- 32 143 O 3 33- 36 160 I 37- ~t 13n e 3 41- ,4.13S e I 6;- *q 134 o 1 6q- S~ - 132 | 2 $3- $6 130 | 4 $7- 6e 1~6 I 3 61- 6* 123 | 6 ~- ~ 1|6 t o 6q- ?Z 108 l q T1- ?~ q9 3 S 77- BO q| | ? II- 81 ll l II 8q- Aa 71 I II mq- q2 ~0. I 7 q3- q6 52 O . 6 q?-lOO ~I e l~ IOI*104 32 O IO IO~-IOO 22 O 3 1oq-I12 19 o ll3-ll~ 13 1 $ ll~-12O~ 0 2 121-12~ 5 o ! I~q-I~O 3 O I 12q-13~~ O I 133-138l | I REPOPT PO~OI -31- TABLE L3 H~L / .P~ilNT TUI4OUP5 H Ol oP. Im,? 0 0 I~,7 O 0 149 0 6 149 0 3 144 O 0 1+,4 O I 143 I) 3 I~O O ? 13n O 3 13.q t I 13~ O 13~ o 130 O l~ 0 3 I?..1 o ~, 117 O II Ioq o q foe 0 -~ 9q o ? nn O 13 75 O II 66 O II ~6 l SO 0 l q )~J 0 12 23 O Iq o f, 1.1 o 0 3 3 0 I n I | 0 I + 76/06113, PAGE PEnNAN~NTLY I~GA[SS(O L~SIONS ONITI(O P(PLICP~£H| ANIMALS |NC1L.U(~.O q& 10TM. ~ Ill 0 I,n • MO, Or AN|UtLS iT PlSK AT IH! nf~lllll|UO OF T~P TI~( P[~|O0 O| u r/O, OF iNIUILS 8(COMIN~ TU+4OU~-B(IA|NO flUgI~IG I~M( TTH[ P[PlO0 D~ • ~3. or INIMtL$ DYlgfi OIJ~I~G lgr. TIH[ P(+|OO UITHOlll n[COMING 7UNOUit-PfARING TIV~ PF.~IO~ J~ OF FOUR V(r~ DUP~TI~I

-32- ( ...+ n o L-- --I I z Z --t > .....t 0 > 0 t"" --1 > -t 0 z TABLE 14 O-A,T, CO, Q.ANO 0,0, PRQJ[CT JANUS INC|GE~NIC( Or N(¥ TUNOUP-REAI~ING ANIMALS fXP~nI'4(KT 096 060 RIrPORT ItDYOI [XPT Bqt6 P[CONST|TUT[O SMUT C 60MG TlU~ ALL TUNOUR5 PERIO0 N 01 02 I- 4 ISe O ) S- 8 I&? e 2 o- IZ 145 t I 13- 16 14S 0 I I?- ?0 . 14S 0 3 21- ?4 I6Z 0 Z Zq- Zn 14e 0 0 2q~ 3z l~e o o 3~- 34 I~e 0 I 37- 40 13q 0 ~1- 6~ 137 0 ! 4q- ~R 136 0 3 6q- 52 133 3 4 53- Y6 126 0 * ~?- 6O !~2 | 4 61o 6~ 117 0 S 6~- 6n 112 1 4 • q- 72 |07 0 JO T30 76 97 0 0 77- ~0 nq I 4 ~1- ~ n4 I |0 A~- ~ 73 0 14 he- q? 5q . | |Z q3- q6 66 0 , 13 q70100 33 0 4 Iq|-10~ 2q 0 7 !~5-10q 52 0 0 19q-It5 14 0 6 I13-I16 8 0 I 117o!50 7 i 0 1Z!-124 7 0 3 12Ro158 4 0 3 I~Q-13~ I O 0 133-136 1 0 0 13v0140 I 0 0 141-166 I 0 0 I&q-14n I 0 ! ~iLI~CNAN1 TUNOUWS N O1 O~ 150 O 3 147 0 I~S 0 I + I~S 0 0 1.5 0 3 I~? 0 1~0 0 0 I~O 0 0 I~O 0 I 13~ 0 Z 13? 0 I 136 O 133 l 4 IZq 0 1AS 0 A 151 0 S 116 0 S Ill 0 !! 100 0 7? 0 I~ 63' 0 l~ ~q l I~ 35 0 31+ 0 Z3 0 0 lY 0 6 0 I 0 0 n 3 S 0 * I 0 t I 0 0 I 0 0 I 0 0 ! 0 ! 76100113. PEPMII~NTLY R£GR~SSEO LESIONS O"|1T~D R(PLAC~MEH7 ANTNALS /NCLUOFD PAGE !01 i. TOTAL B |~e 0 1S0 t; • NO. OF INItiALS AT RISK IT THE n~Ol,'mlNO Of" TI4r TIXT Plr.nl0r) +. o, ,,,+,, ++,+ ,++,.o,+ +,+,., ,,+. +,oo HO, Of INlt4AL5 DYING DIIPI~G THr. Tlu[ PF.OlOq MITHOUT AECOMIHG TUUOI/I~-RFIItINS pEI~TO~, apt qf" IrOUP VElrt+~; rJ~tPIT|(~x

c~ C~ 0 t" I Z Z © >. © .-] > © Z ,) • ( P-loT, COo R,AND 0,0. PROJECT JANUS REPORT |NCIDENC~ Or HEW TUeOUfl-P[ARIHG ANIMALS (XPFn|~ENT qqT OkO EXPT Bq/T REPEAT OF EXPT 93 &OHG Tlm~ aLL TI, P4OUP~ PERIOD N Di D2 HAL|r, NANT TUHOUR$ N Ol I)2 I- t 158 0 I1 1S~ I 1| ~; A 141 I 2 167 0 ? q- 12 I&S 0 O 14S 0 0 13- !~ I&Y 0 ] 14S 0 '1 IT- 2B |~ 0 3 166 0 3 21- 26 161 I O 141 O P 2q- 2+ I*I O O , 161 0 0 26- 32 I+1 O l 141 0 ! 33- 36 160 O O 160 0 0 37- 60 160 I 2 140 O 2 61" 46 + 13e I 2 I)n o 2 4~- 6P 136 0 1 136 0 I 6q- S2 135 0 3 135 0 3 $1- 56 132 3 + 132 o 6 $7- 60 12S 3 3 12n 0 3 41- 66 Ilq 2 3 I2S 0 3 +m- 6e llm 0 I0 122 0 10 6q- 72 106 3 7 112 0 ? 730 76 94 I II lOS 0 12 TT- 80 83 S ? 93 I R ~1- 86 71 1 S 14 0 q .~- 8q 6S I 7 76 ! 10 Aq. q2 SY . 2 0 6~ O 10 9~- q6 6Y 0 q SR I 11 91-100 30 I 5 6~ I T 191-1e+ 3Z O 8 3m Z n IOq-IO~ 26 2 S 2~ 0 19q-112 IT I 6 22 0 p 113-116 I0 O 5 14 I S 117-120 S 0 I n 0 2 121-126 6 0 O 6 I 0 12q-12q 4 0 0 S 0 0 IZq-132 4 O 2 S P 3 1)3-136 2 0 ! 2 0 1 137-160 I 0 I I 0 I ( 75106113. PlOE toe PErmANENTLY R(OR(SS~D LESIONS ONITTTD REPLJCEMfHT ANIP&LS IHCLUI)~D o • . TOTAL 25 133 8 ISO H • NO. O~ dM[qALS AT gISK IT TM[ R[OINMIMO OF Tier TIM+ PFQI00 01 • qO. 0~ &N|MILS R(~OM|N~ ~IJNOIJP-O(I~IN~ DURING THE l|W[ P[RIO0 02 : NO. 0¢ ~HIqALS OYlN~ fl,PlNO Tl.qT. TlUE PEqI00 ~ITHOUT P~COml~6 TU~OUP-PF:RI~G Time PERIOfl+ AP~ OF POUR WEEK5 OIJRATIO~

N o I Z Z @ 8 r- M © Z • ( -34- B°i.Yo CO. R.ANO D.D. PROJ£CT JA|~US TflTILS OF TUHOUR°B[AR|NG AH|qlLS ~XP~R|~[NT IqO 901 [XPT Rq UHTP[AT[O CONTROL ~q[PORT Rn4JO| CLASSIrlcA;ZON I. HOL(SIOHS ~. ALL L(SI~IS P[ImAI~NVLY I~'OPESS[O ]. iLL LESIONS UHCHARACT[RI~ffl ~. SON[ LESIONS P[PMAN(NTLY I~GN[Sb'~Oe TH[ PENA|N|H(~ L($|ONS |[|NG UNCNARMCTFRIS/O q. AT LRAST 014[ R[141GN TIn4041~. PUT NO OTHER TUNQUR 6. AT L[JST 0N[ TUN(NR Sl~l~fl T~[ rlWST SIGNS or NILIGHtNC¥, NIT NO HALIGN&NT TUHAUR T, AT LEAST 014( MALIGNANT TUN1UI~ TOTAL AN|M~LS 617/glTgOl CLJSSIFICAT|OH I, P[PNAN[HTLY R[GIR[SS[O ~, UI~HARACT[RI~[D ~. ~'HION • . r|RST SIGNS OF NAL|ONANCY So NIL|ONAHT LESIONS TOTAL L[STONS TABLE, 16 TOliL I O 0 o 0 0 t&n TOTAL I 0 0 0 o ( REPLACEN[HTANIHILS INCLUOI[D P[RC[NT I00.0 0,0 O.I 0.0 0.0 ~O.O 0.0 P~P~NT 0.0 O.O o.o O.O o.o PAGE

t~ :> o L" I J Z Z -.] .-I @ N (.-,) © [-. --] ~> -] © Z C 9-A.T. CO. II.ANO 0.0. PROJECT JANUS REPORT TOTALS OIr TUNOU~-t~EARIHO AHINALS r_xPlrRlPENT 090 90~ [XPT O~ AC(TON~ TlqqE'AT[O CONTROl. JNINALS ,R,m *,~dJ,ip 4, nOSOl CLASSff|CATiOH 1, PO L[S|ONS 2, ALL LESIONS P[IOHJN(MTLY IBFOIt'ESS[O 3. ALL LESIONS UNCHARACT[aI~£O i. SON( L[S|ONS p[RqAH~NTLY P~fdl[SSrOg R(MAIN|NG L(S|0NS 01[[1¢~ tlNCHdltACTl~ll|.e)[O $. AT LEAST ONE M[HION TUmOURo PUT NO 0T~(R TUHOUR ~,. AT LEAST ~ TU~OUR SHOilN6 T~ fiRST SIGNS or MAL|f)NAMCY, MIT ~ MAL|GNAqT TUI4OU~ T. AT LEAST ON[ MALIGNANT TIJIAOIM • TOTAL WIHALS -35'- TABLE 17 TOT AL 14a 0 0 0 0 0 0 4p4p~.* I'-n ,iHDW~ ( ?6100113. R~PLAC(H[NT AHIHAL3 IHCLUO[O I~I~CENT 140.0 O.O O.O O.O O.O 0.0 PAGE CLASSIFICATION |. P[PqAH(NTLY N[gHH[SS[D 2. UHCHHACTtRI,',~0 3. n[HlON 4. f|A~T S|SHS OF MAL|QMANCY 9. HALIONANT L[SIGNS TOTAL LEA|OtiS TOTAL 0 0 0 0 0 0 P[RCEMT O,l i.ll 0,II lhll 0,0

) Z Z © 0 © Z . ( fl'A.To CO, ReAIqO 0,0. PROJ[CT JINUS TOTALS Of" TtJP(NJI~-B[AR|NO AM|PALS [XPrRIIq[NT 09] Ok| [XPT Oq/I CONTROL tONG ~POPT ROSO! ANIMALS CLISSWr|CATION I. NO L[SIOHS 2. iLL L[StOHS P[f~NAH[qTLY Rl[Glfl[5S[9 3. aLL L[SlO~S UNC~AnACTEnI~n &, SOil( L[S/OHS P(PMJI4[NTLY P[~R[SS[O, THI[ P[HAININfi L(S|ONS 8[ING UIqC~ARACT[RISI[O S, AT L[AST OH[ P(HIGN TUHOIW, RUT HO OTNER TUHOUR 6. aT LEIST ON[ TUeOUR SHOVING T~[ F|RST SIGHS OF NALIONiNC¥, I~JT NO NALIGNAHT TUMOUR Y. AT L(AST ON[ N&L|OMANT Ttpouq -36-' TABLE 18 TOTAL iNINALS CLASSIPtCATIOH I. PI~MiNI[NTLY ~[GN(SS[D ?. UNCHaRACTER|S[D t[S/ONS $. ADIIGN +. FIRST StON5 Or NILI~iNINCY S. NNI.IONANT TOTAL L[SIOUS TOT&L 75 9 O 0 4E O 22 14~ TOTIL 26 I ?S o 4T I*q ( 76/00113. R[PLACEH[NT ANTMALS |NCLLS[O P[nC[NT "SO.T 6.1 e.O o.e 25., 14.9 P~c1[irr IT,i ,? se.3 0.| 31.S PaG[ 16 ." w

Co N o t- I z Z > O > O > O z O*A.T, CO* II.AN9 9.P* PHOJ(CT JANUS TOTALS oIr TUHOUIt-II(ARIN6 ANIMALS (XPT-I°[H[NT eq| 060 [XPT oq/| COHTIIOL 6OHtD P[PORT AwrNaLS CLASSIFICAT|OH !, NO L[S|ONS 2, ALL L[SIOHS P~It4&N(NTI.Y P[glql~SS[O ~. ALL LESIONS UNCHARACTER|S[O 4, $O~ L[S|ONS P(ItNiN~NlrLY P~SS~0o T~E R(MA|N|NG L(SIO~ e(P~G tmCPanACT[RIS[O So AT L[AST ON( flLrN|GN TUN~, OUT NO @11~R TUNOUR ~, Al L(AST ON( TIIP4OUII SqOvlNG T04( rlgST SIONS OF" MAL|GNAHCYo RUT 140 NAL|GHaHT TUNOU~ 7, AT L~ST O1~ MAL|6NINT TII~q~IID • TOTAL 4N|HILS TABLE 19 mOSOl TOTAL 53 q 3 I 0 3| leaeqmeegw 76/00/|3. flEPLAC~H£HT ANIMALS /NCLUOEO P[ACEHT 42,6 6.1 2.0 .T 27.T ~O,O ZO,9 PAG[ ~4 CI.aSSIFICATSON |, P[flNiNI~NTLY fl[Ott~S$(O ~, UIHCHagACT(~|S(O L[SfoNS 10 3. BENION I0~ 46,| 1 61zZ lr cfl i 4, rlflST SZflNS OF HAL|ONANCy S, HALIONANT TOTAL L[SIOHS 0 ST 2In 0.0

• -38- ( ( N o ! Z Z 0 $ >. m © Z F-~.T. CO. P.&NCI O,D, PqQJ~CT JAHUS R[PORT t TOTALS OF TUHOUR°0EAn|NO AN|HALS FXP~alH[HT 092 040 [xPT ~q/2 [XTAACT[D TOfliCCO 44Nfl AN|NALS . . TABLE 20 ROSOI CLASSIFICATION !. NO L(SIONS ~, M.L LE$|ONS P~NM~NTLY I~OR(SS(O .% *LL L[S|ONS UHCHARaCTfRI.~[O *. SON( LF.S|ONS PI~RNaN~NTLY 1~OR[SSI~e TH[ I~MA|NINfi L[SIONS g(INC~ UNCIeARACTI['R|S[O S, At L(AST OH( B(NIGN TUNOUPt BUT NO OTI~R TUNOUR 6, /it L[AST ONE TUNOUR SHOVING THE IrIPST SIGNS OF MaL|ON&NCYt AUT NO NiL|GNaNT TUHOUR ?. &Y L~AST 0~[ HAL|ONiNT TUUflUI~ TOTAL AN|NALS CLASSIIFI¢AT/OH |,- PEnHiN[NTLY I~el~SS[f) 2. t/NCH/u~ACT[It| 11~[0 3, II(NtON S. FIRST SIGNS Of' /4ALIrOMANCY ~. HAl. ][GNANT L[S|ONS TOTAL L[SiO~S TOTAL 105 2 ! 2S 0 & |49 TOTAL Iq 6 37 0 S 76/08/|3. PEPLAC[~NT ~H|NALS INCLUD[O P[RCI~'.NT 70,S lq,ll 1,3 ,T 16.8 OoO 2,7 P[RCENT 31.7 6,7 $3.3 0.4 8.3 PAGE ~4

-39- ( ( N o E- l Z Z © N 8 © Z R-A,T, CO, R,JHO D,D, PROJECT JANUS TOTALS OF TU~Dt~-fl[A~INO ANIMALS EXPF~IN[HT 092 O~0 RI~POAT AOSOl [XPT Bql2 EXTRACTED TOBACCO 60MG AH|MALS ,D~mmemm CLASS|F|CATION I, HOLESt0NS 2, ALL L[S|Ol(S P[RNANGNTLY n[611i[SS[O 3, M.L L[S|OHS tA4CHlnACl~.nl.q~.O &. SON[ L[SfONS P[pNiN[NTLY P[Pn~.SSTO, 17q[ R(HAINING LFSI0N3 |[ING U~CHAPACTEmlS[O S, AT L(AST ON[ KMIGN TUNOI~, gUT NO @TH[R TUNOUR N, AT LEAST@N[ TUMOUA SHOV|NG TF~' FIAST S|6NS OF HAL|GNAHCYt nUT N0 MJLIGHINT |UHOUg T, iT. L(iST ON( MALIGNANT TtP~m TOTAL ANIHALS TABLE 21 CLASSfFIC4T|ON I. P[AHAN[NTLY ~GR[SS(O 2, UI~CHAPACT[R|S[O 13 3 27 0 I0 TOTAL 36 3 7610~I13. REPLACEMENT ANIMALS INCLUD[~ P[OC[NT 64.2 2,0 O,0 ll,Z ~|.0 5.8 P[ACI~NT )S.6 2.0 PAGE ~2 ° ~. PTNIGH &6 47.S ** K|PST SffiNS OF HALI6NANCY 0.0 O0 / llqOI S, HAL IONANT TOTAL LrSIONS I& ou o ~o iol 13,9

N @ ! Z Z 0 N 8 © Z ~-A.T. CO. P.ANO O,O, PROJEC~ JANUS TOTALS Of TUNOUR-qEAPINO AN|qALS (XP~P|H~NT 093 040 P(PORT [XPT Bg/] (XTRACT(O RETUOHED 40HG AN|NALS TABI,E 22 AOS~I Ct.ASSIF/CAT|ON I, HO L[Sl~S 2, aLL LESIONS PEP~AN[MTL¥ ~61~SS[O ALL LFS|ONS UNCfliRACT[~|~D 4. SOM~L[$|~;S P(flUAN[NTLY ~6g(SSt'D, TI~[ P[~A|NIHG L[S|ONS B[/NG UKCHARACT~'ItIS(O ~. AT L(AST ONE A[NIGN TliJl4OUn, IM/T NO OTHER TUNOUR ft, AT L[AST ON[ TUHOQ9 SI~Oe|HG THE rIPST SfGHS Or HALIGNANCYo Hilt NO NM.|GNtUT IUNOUR T. AT L(AST ON( HALIGNINT TUUOUa TOTM. iNfNtLS CI.ASS|F|CAT|ON |, P(RMAHENTLY I~GR(SS[O 4, ~lPST SICKS or MiLIeNaNCY ~. ~M.IONAHT L[SIONS TOTAL L[STONS ]0 0 29 2~ Nm~ |*T TOTIL 27 g ~e 0 2q 76~00/13. PEPLACEMF'HT AN|MiLS |NCLUD[O PEACENT ST.! 6,11 2,T 0.0 19.T 13,6 P[PC(NT 2~,9 ~,0 4~,S e,O 2S.7 PiS(

( C') o L-' | Z Z -] 0 > © [-- .-] > © Z R-A,T, £0, It.ANO 0.0, PROJECT JANUS I TOTALS OF TUMOUR-fl[AI:IING ANIMALS RE'POInT [XPF~IMENT 093 060 [XPT Bq/3 EXTRACTED PETUI~O 60HG TABLE 23 n~el ANTMALS CLASSIFICATION 1. NO LESIONS ?. ALL LESIONS PI[RNAHENTLY I)[GoESSED ~. iLL L[S|ONS UNCHARACT[R|S[O 4. SOME LES|ONS PERMANENTLY I~ql[SSEO, THI[ PEHAININ~ LESIONS RE]HGUNCHARACT£RISEO 6. AT LEAST ONE PEN|GN TUI40~m, qUT NO OTHER TUMOUI~ 6, AT LEAST ONE TUNOUR SHOVlHG THE FIRST SIGNS OF MALIGNANCY, mlT NO MALIGNAHT TUMOUR 7, AT L£AST ONE NALIrOH4NT Tt~OUR TOTAL ANIMALS TOTAL nq q ! .0 26 0 ~2 |AT 76108113. PEPLACENENT ANINALS INCLUDEn PEI~C[NT 6O,S 6,1 ,? 0,0 17.7 ~'0.o 15,0 PAG£ $8 CLASS|FICATION |, PEPNaNENTLY ~I[6RESSEO ~. UNCHAAACTERISED LES|ONS TOTAL 31 2 P[~CEN1 24,4 1,6 3. RENION S! 40,2 &, FIPST SIGHS Of MALIGNANCY 0,0 S. MALIGNANT TOTAL LESIONS 43 luau, ol~ !77 33,9

o ! Z Z @ c~ 8 F" © Z A-A.T. CO. R.ANO 0.0. PROJ[CT JANUS I~PORT TOTALS Oir TLmOUR~HEaPlNO ANIMALS £XPFPlqENT 094 04e EXPT Bq/4 RECONST/TUYED SH[ET A 40NG CLASSTrlCA;IOH I. NO L[S[ONS 2. ALL LESION5 PEP~&flI[qTLY q[61tl[SS[O ~. ALL LES[0ffS UNCHIRACrEffI~LrO PEPalNIN6 L[S/ONS 8lING UNCHAPACT[tlS[O IN|ICALS S. AT L[AST ON[ I~I[NIGN TWIOUQ, BUT NO OTH[R TUHOUA 6, AT L[AST ON( I'UW4OUA St40Vl~ TH[ rlPST SIGNS Of" MALIGNANCY. AUT NO NaLIGNINT TUHOUR T, AT LF~AST ON[ MIL|GNANT TUuOIIi~ TABLE 24 RO~O 1 TOTiL AHINKS TOTAL II0 8 ! 0 2e O 8 147 wens C 76/08/13. R[PLAC~MENT AN|NALS [NCLUOFn P(RC[NT S.4 .7 0.0 13.6 S.& PJG[ 66 CLJSSlr|CJTION I. PEPHA~NTLY P[flRESS[D ~. UflCHanACT[RIS[O L[S[0~S TOTAL n 1 PEPC[NT 19.0 ?.4 3. Krlfl0N 2S 59.5 4. firST SIGNS Or HAL|OHaHCY O.i q. MILIGNiHT TOTAL L[SIONS 4~ Iq.@

cO r'--I N o ! m Z Z @ N © t- in @ Z P.'A.T, CO. II.ANO 0.0. PROJECT JANUS t TOTALS OF TUNOUP-SI[AnlNG AHINALS [XPFPI~rHT 094 060 -43- TABLE 25 I~'PORT ml)Snl [XPT 09/4 gl~COHSTITUTEO SIq[[T 4 60N6 AN|NALS ~I.ASSIPICATIOH !, NU LESIONS 2. ~LL L[S|ONS P~RNAM[Hll.Y I[Gm[SS[O ]. ALL L(SIOHS flNCHARACIlr~IS[O 4, S~4[ LESIONS I~PNA~HTLY A[Oflt[SS[O, THI[ P[MAINING LESIONS filING IINC~,RACT[R|S[O g, AT L(AST ON( B(NIGN TUIAOUg, BUT NO OTH(R TUHOUIq 6, AT LEAST ONE lruMOUIt SHOMIIM TH( (rlIIST SIONS OF' MALIGNANCY, RUT HO MALIGNANT TUflOUR 7, AT LEAST ONE ~ALIONANT TlleOUR TOTAL ANIMALS CLASS|FICATION !, PERf4AN(NTLY a[GR[SS[O L(STONS e*omo~om 2. UNCHAmACTER/~[O 3, 9[NI~ A. F1RST SIGNS OF NaLIOMANCY S, NALrGNANT TOTAL LEa|fiNS TOTAL 1]2 6 3 2 IS 0 |6 TOTAL 21 16 20 0 7~ 76/0fl/13. P(PLAC[M[HT ANIMALS |NClUII)[O P[Pf~HT 73.7 3,,q 2.0 !.:3 ;;.9 ioO q,,2 P[nC[NT 19.2 27,& 4,0 2&,7 PAGE ?3

> N 0 F" ,--I | Z Z > @ > © w J © Z • ( R-A.T. CO. m.ANO 0.0. PRO~CT JANUS I~PORT TOTALS Or TUI~)U~-~AOING AHIHALS EXPE~|~[NT 0g~ 040 [XPT ~91S A(CON~T|TUT~O SHI~.[T R 40NO PHIHALS CLJSSlrlCATTON !, NO L[Sl~ i 2. ALL L(S|ONS III~ItNM~NTLY P[GPESS[O 3, ALL L[$;01i$ IINCHaflJCTtTRI~FO SON| LES|ONS P(gMJN(NTL¥ P[GRII[SS~O, THE PENiINtNfi L(S|ONS |[|NGIINC~ARACTEA|SEO q. AT L~AST ON~. fl(fliGN ~lHmm, RUT NO OTHER TUI49~ ~. AT LE&ST ON( TUNOUff SHOV|NG TH( rlnST SIGNS Or NJLIGNiNCY, ~IT NO MALIGNANT TUflOUP 7. AT LEAST ON[ NALIGNJNT TIPOUI~ -qq- TOTAL ANINALS TOTAL 125 q 2 0 O 0 3 ~mbaew4,. |4; 76/0~113, ~EPLACEHENT AHf~JLS INCLUDEn PEPC(NT AS,O 6.1 1.4 0,t S.4 ;, o,ql 2.0 PJSE CLlS$1rfCiflON !. I~PMJNI[NTLY REfloESS[D ~, UNCHA#ACT[WI~ED TOTAL 12 3 P[I~NT 41.4 10,~ .1, AfNI~ !0 3&.S *. ~I~5T S1flNS OF MILIONaHCY ~, HALI~INT TOTAL LESIONS Nw o ?q

N o I Z Z 0 N 0 I © Z • ( B-A,T, ¢0, R,ANI) 0,0, PROJ[CT JAHU5 * TOTALS OF' TUNOUR*II(AI~|NG ANIMALS EXP~9IHEMT 09S 061 R(PORT [XPT 19/S RECONSTITUTEO SI~[T A 60HG AHIqALS CLASSIFICATION I, XOL~SloNS 2. ALL L(StoNS P~RMAN[MTLY R~8t~SS(O ), ALL LESIONS UNCMARaCTERI.~[D 6, ~ONE L[SI@NS P[RMANI~.MTLY PEfll~[SSLrO, THE e(MAININGL(SIO~S BEING ImCNARaCTERISEO S, AT L(AST ON( 9(H|GN TUN~M, OUT NO OTHER TUMm/R 6, AT L(AST Ol~ TUHOUII SHOU|Nfl TH[ FIAST SIGNS OF MALIGNANCY, RUT HO M&LIGHaNT TUMflUR 7. AT L(AST ON( MAL|GMiNT TIWOU~ TOTAL AN|HALS -t,5- TABLE 27 ROSnl TOTAL 4 0 tO 0 S IIIII 1ST II 76/08/13, REPLACEMENT ' ANIHALS INCLUI)[O PEI~CENT ~II.S P.,S !.3 O.I |l,S 3,2 PAGE 8R CLASSIFICATION I. PEPqAN[NTI.Y I~II.r('~I~[SSI[D ?. UNCHAIlaCT[II | .'~[D .'1. ~[NIGH A. F|RST SIGHS OIr HM.|OMANCY ~. MALIGNANT L[SIONS qm 4u,,~Qw IOTAL LESIONS TOTAL 23 0 ? llIIl ~T PERC[HT lO.l| 62,2 I.I I8,q

• C C ~> o I Z Z --] 0 ~> 0 Z B-A.T. CO. R.AHD O.D. PROJ[CT JANUS TOTALS OF TUI4OUR-E[An|NU ANIMALS (XPFR|I4FNT 096 040 P[PORT [XPT A9/6 RECON~TTTUT(D SH[[T C 40NO ANrMALS e TABLE' 28 ROSOl CLASSr~ICATIOIq I. NO L[SIO~J P. ALL L[SIOIqS P[mNINENTLY NFOI~SS[O ). aLL LFSIONS UNCHaflACT~RIS[O ** SON[ L(STON~ P[WHaMNTLY N[C~RIESS[I), THI[ P[MilNl~fi L(SIONS OETNG ImC~ARACTt'IITS[O ~. AT L[aST ON[ B[NION Ttmmln, ~UT NK) OTH[R TUNOUA ~. aT LrAST 014[ TUI4OUR SHOVING T14[ FIPST SIGNS OF N/~.IGNANCV. NUT NO NALIGNAHT TUHOUR 7. AT L[AST ONE MAL|GNiNT TUPOUR TOTAL AMTNALS CLASSIFICATION I. P[RNJNk'NTLY I~GR[SS[D ~, UNCHARACT[RI~[1) ~. q[H|GN ** fIRST SIOHS OF MaLIOMANCY S. PAL |GNaNT TOTAL LfStONS TOTAL 4 I 0 T 0 O m~maa, 14n TOTJL 6 I 8 0 0 . t ,me w T610q113* REPLAC~H[NT ~NTNALS INCLUDED P[RC[NT 2.7 .? 0.0 *.7 0.0 0,0 I~[PCtNT 40,0 6.7 S3.3 0.0 0.0 P~O[ 9~

• ( ( N o I Z Z © N 8 r- © Z . ,J 80S/S SOI R'A.T. CO* It,AND O.O* PIIOJ[CT JAr/US REPORT TOTALS OF TUNOUI~*GEAII|MG ANIMALS [XP[I~IM[NT 006 060 ExPT B9/6 P[CONST|TUTEO SHEET C 60146 ANIHALS CLASSII ICAIION |, HO LESlOHS ~, ALL LESIONS PERNANENTLY 1~61~[SSED 3. ALL LESIONS UNCNAIqACTEIIII~I[D 4. SOME LESIQNS P[PHAN~.NTLY REm*[SSl.rO, T~[ REMAINING L(SI0HS KING UNCHAPACTI.rRISI[O 5. AT LEAST ON( 8ENlflN TIIleOINt, gUT NO OTHl~fl VUNOU~ 6. AT LEAST ON~ TIJ~Ug SHOVING THE IrlRST SIGHS Of MALIGNANCY, RUT NO flALIGNANT TUHOUfl 7. AT LEAST ONE 14ALIGNANT TtWOIm TOTAl. AN|MALS LESIONS CLASSIFICAT[0H i. PEPMiN[NTLY ~[GqESG[D 2. UHCHAPACTEAI~[O 3. R(MION 6, FIgSY 5|C, NS (He MALIGNANCY S. MAL|~NaNT TOTAL LESIONS TOTAL 134 mw~m 150 eneNsene* TOT AL Io I IO 0 O wo mm 71 T6t08113. PEPLAC[N[NT ANIMALS TNICLUD[D PEPCENT 69.3 S.3 .T 0.0 4.7 0.0 0.0 PEnCENT &?.& 6.8 47,6 0.0 0,0 Page 102

-48- ( ( o:} >. ..-I N o t" --I ! z z > .-] 0 >. (... .-] ;>. -.] © z M-A,T, CO, P,ANO O,Oe PROJECT JANUS R(POqT TOTALS OF' TUMOUII~-OEJm|NG ANIMALS EXPERIMENT 097 040 (XPT 8917 R~'*PEAT OF EAPT B3 40NG flOSO! CLASSIFICATION I, NO LESIONS ANINALS ~o m ,~m,ee 2, ALL L[SrON$ PFRMANENTI.Y PEGnESSEO ], ALL LESTe)NSUNCHARkCTER/SLrD ** SONE LES|ON~ PEI~aNENTLY REOIH[SS[O, THE RE~AINING LESIONS B[]N6 UNC,ARACT[RISEO S, aT LEAST ONE BENIGN TUIs~m0 RUT 110 OTHER TUNOUR K. AT LEAST ONE TUNOUIT SHOVING THE FIPST S[W~S OF qAL|GNAMCYt AUT NO MM.IGNIHT TUNOUR 7. AT LEAST ONE MAL/6HANT TIl~ TOTAL AHIMALS TABLE 30 LESIONS oolm CLASSIF|CAT[ON I. P[tmAHENTLT WlFGIIESSEO ~. UhCHAOACTEflI~f9 1, A[N|GN TOTAL 127 & ! 0 15 0 # ]58 TOTAL 9 2 ?0 76/0A/13. PEPLACEHENT AN|NItS INCLUOEO P~'RCENT aO.4 3,8 ,6 o,e lO.! S.I I~.RCENT 23.1 * S,I Sh3 PaGE )09 • . rlPST S/~S OF ~ALIONANCY 0,0 ~. NAL |(HqANT TOTAL LESIONS ]q 20.5

-49.- • ( ( -.t N o L'- -4 t~ | Z z 0 t~ t- -t O z B'A.T, CO. R.AND OeD. PI~J~CT JANUS fl~)RT TOTALS Or TUMOUfl-g(AA|NG AN|PALS SUWAHY [~P[oIHEHT 09? CALIRRATION/CONTPOL OROUPS CLASSWICArION Z. NO LESZONS 2, ALL L[S|ONS P~.RMAN[NTLY 1~GPI[SS[D 3. ALL LESfONS tmcHAnAcT(RISEO ~. SON( L(S[OHS P[HANL'HTLY nfGl~SS(O, THE P[HAININO LESIONS 9E|NG IWCHAPJCTk'g/SED ~. AT LEAST Ok~ ~[NIGH TtMOI~. RUT NO OTl~fl TUflOU~ 6. AT L(AST 01~ TLINOUa SHOVIHg Ttq( ~'|fST SIGNS OF HALIGNANCYo PUT NO HAL|f',NANT TUI4OUR ?. AT LEAST OH( NaLIGNAHT TIPOq~ TOTAL AN|MaL$ LESIONS CLASS|V|CAT/ON I. PERMANENTLY PEGR(SS(O ~. UNCHAnJCITA l~(O 0 0 0 296 ~oes TOTAL o 76/0BII3. REPLAC(H(HT AHIHALS INCLUO(D P[PC£NT IOO.O e.O I.O O.O e.o ;|.o a.o o.o PAGE 116 3, B(NION 0.0 &, VZ~ST S|r,N$ OF HALIONANCY 0.0 5. MtLIGNAMT TOTAL L(SIO~S 0 o.o

-,] o t" --] ! Z Z >. -] O >. [-- -1 >. -] © Z m • ( 11"4.T* CO. R*JHD D,D* PROJECT JAHUS TOTALS OF TUMOUR-BEAR|EG AEINALS .~'LI~ARY [XP[P[~qEqT gq7 TnEATPENT GROUPS REPORT RD.qOI CLASSIFICalION I, NO L[SIONS ?, iLL LESlflflS PERNMt[NTLY IIEOP[SS[I} 3, iLL LESIOHS UNCHARJCT[RIS[O 4. SOM(L~SIOHS P[qRAMENTLY P~OR~SS[0, TI~ R(MAININIG LESIONS 6(|t~ UNCHAPACTERIS(O S. AT LEAST ON( ~[N|GN TUHOUR, HUT N0 0TH[R TUMOUIt 6. iT L(AST 0NE TUI44UR SHOUINfl TH~ FIRST SIGNS OIr MOI.IGNA.~ICY, I~IJT NO MAL|GNINT |UuOUR ?. AT LEIST ON( P&LIGNiNT TIWOUR -)u- TABLF. 32 TOTAL ARINALS TOTAL 13f13 I07 24 201 0 147 | 946 m m m~ 76/08/]3. R[PLAC[H(HT AH|HALS IHCLI/D[D PERCENT 71.1 S,S 1.2 .2 14,6 ., 0,0 T.6 pJO( IIS CLASSIFICATION I, PERiAAHENTLY RI~GRESSED l, UNCHaR|CTERI~[O LES|OAqS aNnm~o mw S& S.3 3, liEN IWf 4t2 4601 6, FIRST SIGNS Of" NALIONANCY 0.0 ~, HALI6NANT TOTAL LESIONS * 240 23.4

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-51- TABLE 33 DEATHS DURING THE FTRST 20 WEEKS OF JANUS EXPERL~ENT Bg. CONDENSATE GROUPS Dose Group Level B9-I 40 60 B9-2 40 60 B9-3 40 60 B9-4 40 60 B9-5 4O 60 B9-6 40 60 B9-7 40 Number of Animals 148 148 149 148 147 147 • 147 152 Z47 157 148 150 158 Number of Deaths 4 3 5 .2 3 0 2 6 1 10 4 8 17 2.70 2.03 3.36 1.35 2.04 0.00 1.36 3.95 0.68 6.37 2.70 5.33 10.76 Transformed (z) 9.46 8.19 10.56 6.68 8.21 0.00 6.70 11.46 4.73 14.62 9.46 13.35 19.15 The percentage deaths were ~ransformed using the arc sin square root tr~-sformation to homoKenise the variances. The results of this transformanlon are shown ~ the £inal column. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ",,a

~O BAT Co LTD - MINNESOTA TOBACCO LITIGATION

-52- TABLE 34 i i EST~tATES OF NETBULL PARAHETERS FOR JANUS EXPERZHENT Bg. ALL TUMOURS CROUPS B9-1 TO B9-6 k " 2.122330 "~ w- 29.471229f for all groups Group Dose b x 105 B9-1 40 10. 5208 60 19. 4474 B9-2 40 4. 4043 60 5. 8423 B9-3 40 8. 1384 60 8. 6790 B9-4 40 3. 6731 60 4.6015 B9-5 40 1. 4805 60 3. 5277 B9-6 40 • 93908 6O .97727 l.n (b) -9. 15957 -8. 54521 -10. 03035 -9. 74780 -9. 41633 -9. 35202 -10. 21189 -9. 98654 -~1. 12052 -10. 25228 -11.57578 -11.53592 BAT Co LTD - MINNESOTA TOBACCO LITIGATION k.r"l ~m

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-53- TABLE 35 ESTEHATES OF NEIBULL PARAMETERS FOR JANUS EXPERIMENT B9. MALIGNANT TUMOURS GROUPS 89-1 TO B9-6 4.941330 ) k : 31.4000552 v for a11 groups Group Dose b x 10I1 B9-1 40 60 In (b) 17.7380 -22.4527 32.5276 -21.8463 2.8784 -24.2712 7.3924 -23.3280 15.6458 -22.5782 19.5117 -22.3574 5.3223 -23.6565 9.0952 -23.1207 1.6803 -24.8095 3.8166 -23.9891 m B9-2 40 60 89-3 40 60 B9-4 40 60 89-5 40 60 89-6 40 60 Note:- There were no malignant tumours in group B9-6 for either dose level. BAT Co LTD - MINNESOTA TOBACCO LITIGATION k.n "-,I "-4

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-54- TABLE 36 VALUES OF S AND V DERIVED FROM THE PARAMETER VALUES GIVEN IN TABLE 34. ALL TUMOURS Group Dose S V x 10-5 B9-I 40 64 6.0832 60 76 3. 9080 B9-2 40 32 7. 2657 60 40 6. 8466 B9-3 40 53 6. 5123 60 49 5. 6458 B9-4 40 29 7. 8952 60 3~ 7. 3889 B9-5 40 13 8. 7806 60 25 7.086 7 B9-6 40 8 8.5190 60 8 8. 1861 S = ~D1£ 1 V -- ~ (D1i ÷ D2£)(ri - v)k £ The values of D1. and D2. are given in Tables 3 to 14. The values of x 7. k and w are ~iven in Table 34. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ',-O

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-55- TABLE 37 VALUES OF S AND V DERIVED FROM THE PARAMETER VALUES GIVEN EN TABLE 35. MALXGNANT TUMOURS Group Dose S V x 10-10' -- D B9-1 40 22 12. 403 60 31 9 • 5304 B9-2 40 4 13 . 897 60 10 ~3. 527 B9-3 40 26 12. 783 6O 22 11. 275 B9-4 40 8 15. O31 60 14 15.393 B9-5 40 3 17. 854 60 5 13. I01 B9-6 40 O 14. 846 60 O 14. 520 S - [ DI. V - [ (DIi + D2i)(ti - w)k i * i The values of DI. and D2. are given in Tables 3 Co 14. The values of k 1 1 and w are given in Table 35. BAT Co LTD - MINNESOTA TOBACCO LITIGATION r,,o

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-56- TABLE 38 GOODNESS-OF-FIT TEST FOR THE PARAMETER VALUES OF TABLE 34. ALL TUMOURS • Time Period 1"52 53-00 61-68 69-76 77-84 85-96 97+ Observed 75 75 57 75 42 60 47 Expected 83.0 58.4 65.2 64.0 56.7 60.2 45.8 X2 O. 77 4.71 1.04 1.89 3.79 0.00 0.03 Total X2 - 12.235 This table shows the observed numbers of tumour-bearln8 animals, and the expected number calculated usLng the paramlters of Table 34. The total ×2 of 12.235 with 6 deKrees of freedom is 8iKnificant at ~he 91.44Z confidence level. BAT Co LTD - MINNESOTA TOBACCO LITIGATION r,,.n k.m r'~

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-57- TABLE 39 GOODNESS-OF-FIT TEST FOR THE PARAMETER VALUES OZ Z~LE ~,S. m~ZC..~ Z'tmOtmS Time Period 1- 76 77- 88 89- 92 93-1OO 101-104 105-116 117+ Ob 8 err ed 16 36 17 17 ii 35 7 Expected 21.1 30.4 12.7 25.8 11.5 25.9 13.1 Total X2 - X2 1.21 1.01 1.43 3.01 0.02 3.17 2.82 12. 674 This table shows the observed numbers of maLiKnant tumour-bearins animals, and the expected number calculated using the paramecers of Tab£e 35. The total X2 of 12.674 with 6 degrees of freedom is significant at the 92.7OZ level of confidence. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-$8- TABLE 40 ANAL~SXS OF VAriANCE BASED UPON THE LZI~LXHOODS OF THE WEZBULL NODF.~LS OF TUHOUR INCEDENCE ~ JANUS EXPERII~NT Bg. ALL TUHOURS • ~ .| Source of Vaxiamce Between dose levels Between condensaCes/doses ~t~en coudensates Between doses/condensates Condensate x dose interacc£on 5 , , | Total 11 d. £. X2 I 9.43 S 248.12 S 242.79 I 14.76 7.58 265.13 Significance (z) 99.79 >99.99 >99.99 99.99 81.89 BAT Co LTD - MINNESOTA TOBACCO LITIGATION rX.a

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-59- TABLE 41 T~ORZ~NZC RATIOS ~ROM. JANUS EXPERn~NT Sg. ALL TUMOURS Condensates B9-1 v. B9-2 B9-3 B9-4 B9-5 B9-6 B9-2 v. B9-3 B9-4 B9-5 B9-6 B9-3 v• B9-4 B9-5 B9-6 B9-4 v. B9-5 B9-6 B9-5 v. B9-6 Ratio • 320 • 555 • 254 • 142 .O51 1.735 .793 .445 .161 .,~57 .257 .093 .561 .203 95Z Confidence L~w, lCs Lower Upper •093 .275 •058 .O18 .002 1.229 .462 •156 •020 .178 •055 •007 .237 .031 .362 • 092 • 503 • 754 • 429 .294 .154 3. 592 1 • 155 • 710 • 356 • 678 • 456 • 236 .876 .426 .70O The asterisks indicate significant raclos. W e m The cumoriKenic ratio is the raclo of condensate dose levels required to product equal cumour rates in the groups of animals e.E. Bg-1 v. B9-2; ratio m 0.320. This means thaC a dose of 32 m8 of Bg-1 condensate is equivalent to a dose of lOG mE of B9-2 condensate (other dose levees pro race). Alternatively, one m£Kht say ehme Bg'I is 3.125 ekes =re act£ve than B9-2, where the factor 3.125 m I/.320 m 1/tumoriKenin ratio. BAT Co LTD - MINNESOTA TOBACCO LITIGATION c..r'l C..rl r,,,o

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-60- TABLE 42 AN~Ys~s oF V.RL~CZ BASED UPON TH~ LZ~LIUOODS Or TH~ WEISU~L MO~LS OF Tm~ouB ~czS~cz ~ J~Us EXPS~ZMENT ~9. MALIGNANT TUMOURS Source of Variance d.f. . , .,, .... Between dose levels Between condensat:es/doses Becween ¢ondenmaEes Between doses/condeneates X2 Condensate x dose inCersction 5 -- ,, I m m Total 11 Si~ficance (z) 99.50 >99.99 >99.99 99.78 11.89 .... j . 7.87 133.19 131.72 9.34 D- 1.76 142.83 BAT Co LTD - MINNESOTA TOBACCO LITIGATION

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-61- TABLE 43 TUMORIGENIC RATIOS FROM JANUS EXPERIMENT B9. , m, MALIGNANT TUMOURS Condensates B9-1 v• B9-2 B9-3 B9-4 B9-5 B9-6 B9-2 v. B9-3 B9-4 B9-5 B9-6 B9-3 v. B9-4 B9-5 B9-6 B9-4 v. B9-5 B9-6 B9-5 v. B9-6 .291 • 765 .379 • 176 o 2. 634 1. 305 .605 em • 496 .230 .464 95Z Confidence Limits Lower • 027 .383 .058 • 005 1.529 .750 .140 .117 •012 .075 Upper n i, .533 1.O52 .618 ,403 18.600 3. 386 i. 200 m • 765 • 490 • 879 The asterisks indicate significant ratios. See footnote to Table 41. Note that there were no malignant tryout-bearing animals in group B9-6 and so ratios for this group could not be computed. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-62- TABLE 44 CHARACTERiSTiCS OF THE CIGARETTES USED IN JANUS EXPERZMENT B9 Group B9-1 B9-2 B9-3 B9-4 B9-5 B9-6 B9-7 Weisht at Making (g/cig.) 1.05 O. 86 1.06 1.19 I. 05 1.00 1.06 Dry Condensate Delivery Oq;l ~is. ) 26.5 23 27 36 24 22.5 26 All cisarettes were 70 m, in length and smoked ~o a 23 --- butt, The c£Earette circumference was 25mm. The lsmina-stem ratio for Bg-I was 60/40. The 1~na was cut to 56 c.p.i, and the stem to 180 c.p.i. The sheet materials used in Bg-A to B9-7 wsre cut ¢o 60 ¢,p,~. BAT Co LTD - MINNESOTA TOBACCO LITIGATION ¢,.,m

> -4 @ | Z Z > 0 > t-" > 0 Z ~J i ! -63- ( TABLE 45 |-I,t, CO, m,Jq 0o0, wtO.J[Cv JL~S luCtMXCt ~ .~w T~dt~tl~l ~imL2 tstte1~'~tiT I~IO It$ (ItPY. 113. O0.'t( LtV*LL nt*O PtDI~ I* 6 I1- IQ IV- P|I Z5- ~t E*- )it P?- 36 ~I* c.e 61" 66 li~- 68 *** St 6|- 9.li 6~* 40 t*- ?| t)- It 71- It "I- lli IDt. AID lit. tlt ti~- li6 9~*I IPP lel-le6 Im**ltiI It.o-it/ II'~*I,S ! 17*lLPe iZl-ltli |74L-l?q lt~*t2Z | y**t.~.4 l.~/*l*e IL$-i*I |liqP.l|J| ILL ~L's~UNS ~tLIONliMY TI/s~Ts5 # 0! 0~ 755 e $ ~S O 3 IS! O ~ tit O 2*8 l l ?it t i |61 i | ;liY i ~liY B J ~*Y O 0 ~1 I l |liT I I tlit e I ~li6 | • I t65 0 ~ ~¢S 0 ~0 i ~ hi I P ~3n I ~ ~3a o Z~5 e L ~ e L ~3t O li ~ # * L 21. e Y ~I~ 0 ? |I~ e 2 ZI~ t 3 ~oe I ) .}is t ] tos e 3 ~e6 e 3 ~I? 5 I ~e3 e I lfli ) T I*~ I Y l~li I • I~ e t ITli l i l~l O t ISS I II IT~ t It l~t 5 9 . 14¢ l IL~ • l? 150 e 13 lit 3 I] 1~I e 1~ lift 3 I) IS3 I 1~ 9.* O I$ 145 l IS 19 ~ It 09 | lm 61 • 9 Tm ~ q 5~ 0 II t] t II • ) I IS SO e II ~. I ~ 39 ~ li • t? i ~ 29 2 I0 I) P ~ IT l 4 ll l S 11 l S m l I T 3 3 I e I l t I It/e,tT3 Pitt I Pfg'PItttNTLY PtPltlttOifSlO~tlO|tltltO ~t%lct~tu? ¢~I?IL5 I,qtt.t/Ot2 TOI~ ~1 p?li |4 ~L| Ol • I,,5. It ~*:|'~LS i~r~O"'",;'~ l";~.".'t'-?'/.~;*:.~ L",:P!~.~ ,J,s~ fly|" BTmIO~ P~' .' el***, r** ,',*'~,*"A*T P.vp.,~. ':'~'.~.'i'. :*.," Ty,,f. ~,,L'C|~ vleq~vl ,'ir.C~ul~G "V"%*~.-:'tmmt~:O , . I. I: i 1' i I ~',. :

,,-I 0 t"" --I ! Z Z ++ > ..,,.+ 0 >. <+ t'-' "'l > ,.-I 0 Z p ! J I ( I' t+ | j ,,J '+ I J f -64- • TABLE 4~ IILrllllll I IIOSII I~POqS?.~ Vl~[ ~1. Tllmm~ NJ~tr*mA~r Ir~l~s ~PlC~ u OI Ot ~ 01 OZ q* O lSf t ! ~ O I ** It is1 I | as1 e t I1- It I~e i 3 Z~q t 3 |T- F$ ~L6 0 ~ ~66 O I ?m. II lmZ I I Iml e " I I+- 31 141 I I l+t + I 31- 3J 24q l I ?+I l I ~- 61 73~ l I ~3q e I 61- +* ill | l 237 O O .~0 +n Z]+ t I ~37 | I LI- II ~21 I I ?37 e I $1* 5~ 73~ I 6 . ~55 l • il- H 115 $ l P+T I + I~- ~I It; I I I+I I • T,- TI In+ IS 1 114 I l .- m+ I<,,+ II r ;l+ I + el- +L 14S I$ 1 19+ S II , *~- ~ i~i II $ Ill 5 ~7-IIl ~I P F IA~ l II le~-IAL S+q + I IO~ It IZ IPqolPq t~ 3 g nt II 13 l**-lll 3l I I S~ 5 ? lll-ll6 Pl 3 S ~ +P • II'-IpI 17 I I 31 t + I?I-I74 II I l ~0 I 6 IP#*IPI i q ~ I+ + P l~*-l~l +. 1 0 + I I I~I-ILI I I 0 I 0 I I*I'I+1 I I O I I i l~+-l*l l l I + ; l T~rJL IF4 131 ++ |TP FIK It I['I~LIC[H[HT IIII~IL5 |HL'LtlOED t I I i t I L: .I p I. i i. | i i e.

>_+ N 0 t-- --1 ! p.,,l Z Z ++ > O > 0 t-" -.+ G"J > © Z ! +I J i I , I i+ ,J ! I .! i +'+ .+ 11c 01 " -5S- C TARLE ~7 O-J.T. CO. IC.~O D,B, PPO,I(CT J&IEIJ$ INItlOt*~C[ lip ~Iv tUm~-.Plti*lNI A.~I"*LS PtPO~! PO51| txp[lll,,tqlT il))e l+t$ EXI*T. i~l. OOSl[ LtVl[1. TSml I'11o1[ ILL IL~O~NIS PlLlflSl&+t tU~lUe.q l~'.e lOO ~ 01 02 n Ol OE l* *, M~ e Z 15', e I • .- e I~z * 3 +51 I ~1 'I* IZ I*9 II 41 lLq) 41 4 I]* 141, 141 I 3 ~?&4 O $ liP- 25 7+lb l 5 l'-+* O S PI- !+ P+I I i) .+I,I II I i~- lO ;P+,I e "- +r,! e ' ,L • +9- 31' ~)y o q ~jT II ?+ 31o 36 ~31 I I l'~S 41 I • 1- +*~ l)l I e ,~31 e e ++~. 441 ~)e ! 3 +3~ O .1 ,bq* ~I I~41, 5 Q ~PIP~ l 4b .~+- +, lit S I " ~S I i 51- 4,e +It O x Z2I l I 41- 64 lit I+ 3 +19 I 4 4m- 41 le+ + 6 . Z14 tl 6 I~+- TZ IPI I" * ZOS I S ?1- ?~ IS1 I~' S ~O~ I II TT- IS 13* It 3 19] 4 6 ~s- e,. I~* ir * Ju) ) * q~* 80 e? 1t S I1t I 9 I1.. +?. • IX e 3 155 te • q~l* 41 I+I l I I~.1 It II qt*l'~+ It 11 S Ill I 13 I+: -15+ i5 ? I +T 5 5 I+~-Io+ 311' 6 $ l? iS I0 I*~*IIZ 14 3 S 6~ IO + II$-IIS II +' 3 +3 • ~J ll*-IXl II I 3 3~ e T Ill*if4 lr 1 I ll 3 $ IP+oIZn 4 l I 10 2 | 129.13L+ ]. t I ? 3 I 133-1:15 ! l t $ I 8 12/0~173 Pp~C El P[nmINTNTLY g(GqC$$[9 L[510~5 ~111(O R[PLPC.~qtNT IHI~&LS |m~l.I/OI[O t* TPTIL IS? 11 11! lSi ~ • ~/O, ?r ,191;ua~,.~ I~.Vl':O ~'!~T'~r., It'r. ":vtr r[~:O~ W|TH~,IT te[C~vl~fO |Uu13UP'~q[Aq~*~O TI.,+ Irr-;l,.,l.,,~ /.kr :,IP r~J,~q i..rr~m ~*+liP¢.l+:'~.+l i + i; i ! r ! I t 1. r; P I I! t ! I i i I I i Ii I I ! I I I

o [.,.. I Z Z 0 (-., © Z .,w .*.J 6 ;ZSVS01 Q-l.1. ~0, ~,&q0 0,0, PUOJ[CT JI,~US ?ORALS Of" TUnOUQ-e(J~/;~.A JNINALS (~*[f (-~NT 030 ql~qi r.~PT, f13, 005( LFV[L ~Sue TABL[ 48 P[P0NI I~OSt)IL JwI~'AL$ CLASS lit ICJT ]'0~ I, NO Lt'S10"~J" t, aLL LCSIO~J P£m*0akl[mTLY PF.Se[S$[O 3* ALL. 1.(SlO~S UqCwiI*CT[I~|.~[0 4. S0~ I.(SI0*q P[qvi~R~ILV ~1[g.~[$$~9, 1~.. ~(~AI~IHG LE510~S ~q[l~ II-~cPlqAcTrl~IS[D 5. AT LI[&ST ONI[ Lq(q|6q Tu.qQ~I* .qUl' ~O OTI~cq TUI~O'Jfl i, af tipsy 0~. y~-~ s.'o~fq5 r~[ rr,~T srGYs or NaL|SNA.*:CY, ~luIr kO )*AL|G~INlr /U.U~,/R ?, A7 LI~AST 01~ N~t|fi~*NT TIINOUq ¢LAS$~r[CATI~ 1, P(q~ew[uT~y P[fln!SSTP ~, firST SIGHS Or ~ALIg~ANCY S, UiLIGHiN~ TOTJ~ JNI~AL$ L(S!9~5 T~)TA~. LF51C'.'5 TOTAL tlo 16 & 0 13 O" m~e.m~ TOYIL 37 e ]; mm~w~ ~3 l~/eg/T3 S,$ 1.6 i,O 5,1 e,O $,$ PCn~prr 6.0 ~6.0 Z3o3 PkOT 2

> N o ! Z Z > > r- > Z °. *° r O I-AoT, CO, P.ANO O,n, Pqov~.¢T JAk~JS TOTA~ or TUvOU~-~Jmlq6 J~]~aLS ~PC~T AN~vaL~ CLsSSTFICSTICni Z. iLL L[SIC~eS P~D~aN[~TLT ~(O~SStn 3. AL~ L[S|~S UHcq~qACT[R|~[O P&LIS~NCY* gUT ~0 ~AL|G~a~T TU~OUi! ?, IT L[IST 4"4r ~4LiGqlq~ TI~OI.~ ¢tiSS|TICAT|ON L, F~PST $|GKS 9T q~LIO~INCY -67- TABLE 49 qgS~l TOTA~ ~I~iLS TO~JL I0 3 3~ e eS TOTa~ 33 t) 8$ 3 ]2/09/?3 P[nc[~T ~,5 33.3 P~'qCENT ]1.8 &.6 ].1 5t.1 P~G[ |3

N 0 ! m~ Z Z 0 ,...q m @ Z C -68- TABLE SO B*a,T. Cfi. g.~gO 0.0o PPOJ[~! Jl~JS TOTALS or TUVe~-~(Jnll~ AH!MALS (XP£a|U~T ~O gTS ~xPf. B~. COS~ LtvI[L 1S~6 P~PO~T qOS~l ANIN&LS CLaSSlrZCaYIO~ &, e~PS? SlG~S Or ~ISHAgCY TOTSL AH~SM.S L~SfO~S S. ~ALI~&qT TOTAl. OO Y 6 1 *O Io@ ?OTsL *7 IS t~S 6 tit %~I091?3 P(PL~C(~I~qT INIHXL5 It~C~UD(O Pt~CEHT 33 • 4 E.S Z.4 ,& .ll 39.4 | PE~CI[NT !1.9 3~.3 1.5 ~.8.$ Pas( 29 f E t ¢ | I' [ i i I" [ I ! !- t i ! t 1 r i. L i. L

N @ ) Z Z Q [-- © Z -69- TABLE 51 ~*a.T, 20, B.AND OoD, P~CJ[CT JL*C~ TOTALS Qr TU~OUf-~[nWlt~ A~IPPLS 5UW4&PY ~Xp~:v[nT 030 ?~[ITM[NT 0t~U~S m[P~.qT AqT~JLS ¢I.A$S~FtCATIQN 1. NO L[SlONS 2. ALL L[SltWS P[WNA~TLY Pl'Oq[$5[~ 3. ALL L(S:gN5 U~CNARACT[~|S[O 6, SO~[ L[STONS P(ItI, aSC[~TLT t~[SS[O, i~ TOT&~ 13 & q* 2 121~qI73 ~[PLAC[P[HT AN|UALS |NC~)~D .SS,! I.? ,5 1~.,3 .3 PA~[ 86 ! t, i T L T. AT LEAST 09~[ qaLiGNJ~f f~'O(~ TOTAL ANIPALS ?54 o (J -j ¢LX$$IFIC&TIoN l, P[nvINl~N?Ly P[0~[$$[0 4. F|~$T S|~*HS Or H~|~MJNCY ~, ~4L|GN&NT L~510~5 TOTXL 33 Z3* 9 3S~ 15.~ &,4 I.~ 47,&

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-70- TABLE 52 DEATHS DORING THE F~RST 20 WEEKS OF JANUS EXPERXMENT B3 AND JANUS EXPERIMENTAL GROUP B9-7 Group ,,, B3-O25 B9-7 B3-O50 B3-O75 Dose Number of Number of Deaths Transformed Level Animals Deaths (~) (X) 25 40 50 75 255 158 255 254 8 17 II 13 3.14 10.76 4.31 5.12 10.20 19.15 11.99 13.O8 The percentage deaths were transformed using the arc sin square root transformation to homogenlse the variances. The results of the transformation are shown in the final coluum. TABLE 53 ESTLHATES OF WEZBULL PARAMETERS FOR JANUS EXPERIMENT B3 (CONDENSATE GROUPS) AND JANUS EXPERIMENTAL GROUP B9-7. ALL TUMOURS k - 2.870709 "[ w - 29.337135J~ for all groups Group Dose b x 107 B3 25 4.58652 B9-7 40 12.83175 B3 50 33.16753 B3 75 51.30449 In (b) -14.59497 -13.56617 -12.61652 -12.18032 BAT Co LTD - MINNESOTA TOBACCO LITIGATION

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-71- TABLE 54 ESTIHATES OF ~,~ZBULL PARAMETERS FOR JANUS EXPERIMENT B3 (CONDENSATE GROUPS),,AND JANUS EXPE]R.ZHEI~T ,AL GROUP B9-7. HALIGNANT TUNOUtIS k = 3.661590"-i_ ~r- 57.498461J for all groups Croup B3 B9-7 B3 B3 Dose b x 108 25 40 50 75 1. 94724 5. 86056 23. 29572 29.07937 In (b) -17. 75427 -16. 65244 -15. 27241 -15.05065 TABI.E 55 VALUES OF S AND V DERI"VED FROH THE PAI~AI~TEE VALUES Ot~ T,t_SLE 53. ALL, TU'~UP.S Group B3 B9-7 B3 B3 Dose S 25 31 40 25 50 124 75 157 6.7589 1.9483 3.7386 3.0602 s - .~ Dxt v = ~ (nli + o2t)cti - .)k ,~ X Z t The values of D1i and D2£ ace given in TabZe 15 and Tables 45 to 47. The values o£ k and w are 81ven £n Table 53. BAT Co LTD - MINNESOTA TOBACCO LITIGATION O',,

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-72- TABLE 56 VALUES OF S AND V DERIVED FROH THE PARAMETER VALUES a OF TABLE 54. ~qLZCNA~T TIR4OURS -8 Croup Dose S V x I0 14 B3 B9-7 B3 B3 25 40 50 75 8 85 100 7.1897 1.3651 3.6487 3.4389 S - ~ DI. V - ~ (D1£ ÷ D21)(ci - v)k i L i The values of DI and D2 are given in Table 15 and Tables 45 Co 47. The values of k and w are given in Table 54. TABLE 57 GOODNESS-OF-FIT TEST FORT HE P~TER VALUES OF TABLE 53. ALL TUNDURS Time Period ., I- 64 6.5- 72 73- 80 81- 88 89- 96 97-108 109+ Observed 59 40 61 53 43 53 28 Expected 63.7 40.9 47.8 49.9 47.0 53.4 37.6 Total X2 -" X2 O. 35 0.02 3.6'; O. 19 0.33 O.00 2.46 7.002 This Cable shows the observed numbers of Cumour-bear£ng animls, and the expected number calculaCwd using the parameters of Table 53. The cotag ×2 o£ 7.002 rich 6 degrees of freedom is slgni£icanc ac the 51.76Z confidence level. BAT Co LTD - MINNESOTA TOBACCO LITIGATION mamml~ (..r-r oo

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-73- TABLE 58 GOODNESS-OF-FIT TEST FOR THE PARAMETER VALUES OF TABLE 54. MALIGNANT TUMOURS Time Period 1- 88 89- 96 97-100 101-108 109-112 113-120 121+ Observed 34 38 ~8 49 16 26 26 Expected 35.7 34.4 20.3 42.2 19.0 29.5 26.5 Total X2 '= X2 0.08 0.38 0.26 1.09 0.47 0.42 O.O1 2.711 This table shows the observed numbers of animals bearing malignant tumours, and the number expected from the parameter values of Table 54. The total value of X2 - 2.711 with 6 degrees of freedom is significant at the 23.46Z confidence level. BAT Co LTD - MINNESOTA TOBACCO LITIGATION C..m ¢,..m

FIG. ! THE_ MORTALITY ,_CURVES ,OF UN-PAINTED ANIMALS EXPER!,MEN'T,S 130 AND ,B,9, "P~ I4Sl RES'TRIC'~D IN ,JAWIJL5 PERCENTAGE OF ANJHAL~ ~URVIVIN~ I00" 90 SO "70' ~Q d~O" 3O" ~.O' IO, 0 .......... IbO '1~ql " "%,.. . i'''"-. ,. I ' I .... ! I I ' ~ ; Zo 40 ¢.,o llO ~oo i~o EXPERIHE~rAL "r~£ IN WEEK6 BAT Co LTD - MINNESOTA TOBACCO LITIGATION ,% % .I 160 C..m (.m Lm Lm

THE FIG. Z RD. 14-t~1 RE.STRIC,TED MORTALITY CURVES, ,OF ACETONE-PA!,NTED ANIHAL,S" EXPERIMENT3 !~ AND B9 i i IN JAN U,5 PERCENTA~I= OF ANIMALS ,~URVIV I Iq~ 0 BAT Co LTD - MINNESOTA TOBACCO LITIGATION IL | \ %

,JANUS EXPERIHENT {Y:). ,,, WI=I:'K~ I TO ZO IRCLUSIVF=,. % DEATH,5 DURING FIR~T P.O WEE/'~ Fi6.3 RD. 14Sl RE~TRIC.,TED PERCENTAGE OF TUHOURLESS DEATHS &ROUPS Bg- I To Bg- t,,. 6-0 ~-o 4.-0 3"0 2-0 I.O 0 4O DO~E I.EVF.~. m9. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

JANUS EXPERIMENT ~,9. G, ROUP5 Bg--I TO B9-&. NATURAL WEI BU LL -9-0" -I0-0' --II-0 BAT Co FIG. 4 PLOT OF t..n (b') V,~ ALL TUMOUR~. RD. 14~1 RESTRICTED &rt (DOSE LEVEL) LO~ARITH M OF PARAHETER b B9- I o ¢B J~ B9"- G, 4 i i | Ii ~.-K,~e /.,~ (.DO~E LEVEL rag.) 4.094- LTD - MINNESOTA TOBACCO LITIGATION

JAN U5 EX PERIMENT 59. GROUP'3 89-1 TO ~--6. PLOT OF t~ (~b~ Vs MALIC~IANT "rUMOU1R~) &~ (J~O~E LEVEL) NATURAL WEI~ULL -P-.2<) -8.%'0 --P-.5-O N.~ THERE WERE NO HIALIGt4ANT LD~ARI'rH M OF I~ RAMETE R b "TUMOUt~> IN GROUP ~9--~. i ~9- I B9 -3 I iii I| 3-&~ ~n (DOSE LEVEL ~.) 4.(~14. BAT Co LTD - MINNESOTA TOBACCO LITIGATION N ¢..j'1 k.3"1

JANU3 FI6. r~ RD. 1481RI~'T.J~c'rED dANU3 EXPERIMENT GRouP Bc)-7 EXPERIMENT 153. CONDENSATE TIREATE~ GROUP3. OF.ATH5 BURII~3 FII~T 20 .WEEK,5 THE ARC., ~IN 5GIUARE ROOT VAJI~I/IJ~ICE S'rABILI,~NG TRANk.e~ORlUlATION OF "THE DEATH RATES HA~ BEEN USED AI~O SIN A(,9~'o dEATH6,) /100 20' 18 IG i,4. 10 9 6 4. 0 I ~.O X 89 -7 ~ ~m'~~°~ ~ oo ooo~,o omooo° °m ~ poe~~° oo oo~e~oo o .°°--° " ~S ¢~ (DO~E LEVEL,) BAT Co LTD - MINNESOTA TOBACCO LITIGATION 0 --,,j

Fi6. 7 • RD. 14Sl RESTRIC;I"EI:;) JANU~ EXPERIMENT 8ROUP 159-7 JANU3 EXPERIMENT, 153,. CONIZ::~F.N~ATE Ti~.EATEI;) GROUI~ PLOT OF t~-n. Cb) ~ ¢n, (i:3(::~E LEVEL). THE =P3~'= CONFIOENCIF. Rrr~lON~ FOR £m~,b)ARE AL.~O NATURAL LOGARITHM WEll3ULL. PARAMETER - IZ-O ,~ -15.0 OF b ALL TUMOUR~. -14-0 -15-0 I S / / t / t / I 0o 0 a / # t 0 0 O # I / • i# • # • • I / , S 0 / I S / O # I I # Bq-7 IQ i i ~-o t,,n. (.~ L.EVF-L~j:) BAT Co LTD - MINNESOTA TOBACCO LITIGATION "SHOWN. o oj. D i 4..O (.j-i .-...j

Irl~. I, RD. 141~I RF~TRIC, TED ~IANU,5 EXPERIME.NT r.7,R{:)UP B9-'7 ,J.aJ~IU5 , EXPERIMF=~,T !~,~. CONDF..NSATE T,R.EATED GRDUP5 PLOT OF t.,'n.Cb)Vs £'R (}:>O~E LEV'EI-) "I:HE 957,C,,oNFIDtENcF, REGIONS FOR f.,'~(I~ARE ,..~4OW'N. NATURAL LOGARITHM OF WEiSULL PARAMETER b MALIGNANT "ruMouR's - 15-O t .# I / / # / / t / / / I # - 16-0 / ¢ I f #. # # # # • # I # # / a / / # 0 It :s3/~, # / ! ... B~/'/5 •# / ; # 0 / I / # q 0 E F - r'7.0, -m.o B~-7 t | i , m t,~ ~ LEVE~ "rag.) I 4-0 BAT Co LTD - MINNESOTA TOBACCO LITIGATION (_r't

FI6. g RD. ~SJ RF~'rm~.ED JANUS EXPERIMENT Bg. GROUF~ Bc)-I "TO Bg,& TRAmr-~MEO A6E-m'~~D~e.~ TUMOUR ~'E-~ Vs. B~ (~)0~ ~J~V~L) ALL TUMOUR.~. TRANSFOR MED TUHOUR S00" 4.O-O "0' AGI~-"~"I'AN I)ARD 15 E D KATE 6R-.5 89 - P.. ~9-4 GL- 3-&Bq {~ (Dc~E LEVE:L-m~j.) ,4..0q~ BAT Co LTD - MINNESOTA TOBACCO LITIGATION C...m t..r'l

JAN U~ FI~. IO RD~I,~I RE,STRICTED JANUS EXPERIMENT GROUP 89-7 EXPERIMENT BS- CONDEI~ATE "TREATED 6ROUP5 TRANGFORHED AGE-GTANDAIRDI~rI~D "I'UHOUIR RATE~ ALL TUMOUR~. t ¢4 fCx:~ LEVEL) . "TRAN~ FORMED./¢~.-6"rANI~AKDI~I,F.D TU MOUR RATE 50 4O 3O 20 ¢1ode • o'e •,¢e / / / / / / / / / / / / / / J # / / / s dIS3/P.5 4 3"0 44) £~ (I:X:)~SE LEVEL ¢~t.) BAT Co LTD - MINNESOTA TOBACCO LITIGATION

BAT Co LTD - MINNESOTA TOBACCO LITIGATION

BAT Co LTD - MINNESOTA TOBACCO LITIGATION