148/13 3 M MEETING & 28th APRIL, 1969 The futi-e of lona-term skin vaintina tests at Battelle There are probably sufficient funds already allocated to Project JANUS to allow one more long-term experiment (Experiment 99) to be completed, although it may be necessary to extend the contract in time. A new contract will be needed to enable further experiments to be carried out. For the next few years, the long-term mouse test is likely to remain a major test by which modified cigarettes are judged. Inhalation tests are notyet developed, and it seems essential, therefore, that the mouse test should be available to B-A.T. As specified facilities/personnel are required for this type of work, it would be difficult to switch from Battelle in the near future and undertake the work elsewhere. It is suggestedt therefore, that a second "five-year" contract is negotiated with 3attelle. It would be possible to start four experiments in 1970 (Experiments 39 - 812.) It is suggested that these experiments are allocated to the examination of samples of cigarettes by the "classical" procedure rather than examining new forms of testing such as the use of hairless mice or instant condensate. The complete results from Experiments 30 - B12 would not be available before the end of 1973. Consequentlyl we should endeavourl from Experiments 80 - 812, to produce a "package" of results which would help us to design a modified cigarette. In an attempt to remove this statement from te realm of a "slogan", the factors involved in the design of a modified cigarette have been reviewed to draw attention to the gaps in knowledge. Cioarette Darameters c:::o The effects of changes inxerious cigarette parameters have been, or are C:~) currently, being, examined and the results will be available in December 1973. 1.0 cc BATCo document for Province of BritiSh Columbia 2 November 1999 -3- Sheet materials This, it Is suggestedp is the area for major effortg although it is being partly met by Experiments B3 and B8. From the comparisons at Harrogate of Folie 3 and Blend 3 and Schweitzer sheet and control blend together with the JANUS experiments 33 and 34, there is an indication that Drocess can be an Important factor. Further information should emerge from the second series of Lokstedt tests. There would appear to be a case, thereforel for further work on the effect of theprocess used to form the sheet. Perhaps of equal importancep is to determine whether the activity of condensate from the "PCL" is dependent upon the nature of the starting tobacco. Additives The eff-~,ct of adding nitrate to tobacco undoubtedly leads to a reduction in tumorigenicity and indicates that additives provide a possible means of producing a "break-through". It wc~uld seem well worthwhile, therefore, to have one experiment in the B9 - 312 series dexted to a study of additives. Clearlyp if chemical analysis of smoke can guide the choice of additiveg then it should be followed. It is suggestedg however, that there is a case for considering an examination of a series of non-toxic additivesq which we know could be added to cigarettest on an almost purely ad hoc basis. Perhaps, however, this could be amalgamated with a study of the effects of smoke pH. Filters To datep filters have not been shown to reduce tumorigenicity. Some of the current results from Huntingdon, albeit at an early stage of the experiments, can be Interpreted to indicate that a high efficiency filter might be beneficial. Stating the obvious, we should attempt tolake advantage of any results from Huntingdon. CD C=) C IA/S4 1/ 1. 1. 1. 3 21 st April, 1969 CX:) BATCO document for Province of BritiSh Columbia 2 November 1999 174/2 TESTS : LUNG MWURS At the 16th r1C Mdeting, it was noted that, there was some confuslon over the extent to which lung tumours occur In the control animalst (.'.',inute 162. ) To clarify the pcsition, Battelle have sent the following infor- mation. Unpainted Solvent-paInted, Controls. Controls. Num'-_*r of animals In group. 128 128 Number o animals su-_,~ected to 114 25 1 histological examinat' ion. Lung disordexs- Carcinorma of the lung alveolar. 7 Bronchial carcinoma. I Tumours of the alveola:- cells 4 10 of the lung. ..Ixed type malignant tuffours of the alveolar an6 :3:onchial epithelia. Fibroma. Z - I Pneumonia. 36 21 Small cell neoplasns in the lung. 1 2 L;ymphogranuloima of the lung. 1 Lymphoreticuloma of the pleura 1 pulmonalis. %sothelioma o-- the Pleura pulmonalis. It is possible for an animaL to have more than one of these lung disorders. Battelle have given the numbers of animals with lung tumours as . Unpainted controls 16 from 114 animals, i.e. 15.F, Solvent-painted controls: 24 from 125 animals, i.e. 19.25~ Combined controls 42 from 239 animals, i.e. 17.61, CO BATCo document for Province of BritiSh Columbia 2 November 1999 "."hese figures are slmiliaz to those obtain-:?d by Roe at the C"nester 3--atty Resjazch Institute. In a draft of a forthcoming PU:311- cation (TR.C document G 740), Roe reported that 54 of the 400 solvent- painted mice had lung tumours, (i.e.13.55X). (Please note that unt-,1 the paper I's publi5hed this inforretion is confidential.) In the Day publication on the .2irst -Main Experiment at iiarroo-ate 0 Or. j. Cancer, 1967, 21, 56) adenoma -f-the lung is recorded as t'.0 cause of death of 32.~,~ of the animals. in a recent TRC document, G 3615, hoviever, Harrogate have po -.ted out that this is not tne tota-1 incidence si,-.ce lung adenomas were also found in other mice for t-,111--ch a cause of deathwas ascribed to other d1so.-6ers. Indeed, wher, the - 'de, nc., -ice of adeno.-..a of the lung is extracted from the original mouse a ds of t- 'a, n experi-ment, the compaxison w-1 c r .e figures quoted by Roe -a extremely close. I CIA/ S011 1. 1. 1. 3 4 th July, 1969 C=:> 110 %-0 (.-n CO BATCo document for Province of British Columbia 2 November 1999