GR&DC RESEARCH FROGRAMM- PROPOSED REVISIONS FOP, 1984-1986 0 I QR3 liritili Ana-mcan Tobacco Co. Lid. This mwm 1P.-I 1-. .e Shaun la sonauthur6cd BAT Co LTD - MINNESOTA TOBACCO LITIGATION Research Conference, Brazil - AqtLst, 1983 GR&DC Research Programric 85 PROPOSED REVISIONS FOP, 1984 1986 Worh Area 01 Biological Cencrnl The design of cigarettes of reduced biological activity will receive additional impetus undar Project RIO. Initially, activity will centre Oil Lhe deripn oC cigarettes based on the current "state-of-the-art". 11owevcr, as t1v_- inatrix of biological activity against product parameter is not complete, refinement of designs will be dependent on the comple- tion Of necessary basic studies. Over a longer period of time it sbould be possible to capttalise on some OF the current biological research projects (and related tests) in relation to the design of cigarettes of low biological activity. The development of new test methods will b,@t strictly limited to those considered essential to the evolvement oil Projtct RIO. Progrnmnie Rev".sfons 1. 1Yrod%1CL!-, OF rcd%iced biological activi.@y A systeinattc ovk1luatiun of product parameters will be the main activity, a s To nuct the longr-r-tcrm needs of Project RIO, Ci tscu:;SL, da hove . collab-irativc %:urh wlLh the Combustion Group (Work Arca o5) will be initiated. 2. Sidcstrann, Smoke Studies into mutagenic activity will be given nore effort as part of a large programma aimed at deterntning and controlling the biological activity of sidestream smoke. 3. Short-term test related to cancer In 1983 the demand for the first mutagenicity test. the Ames test, excecded expectations and consequently the planned development of a second test, mutation in ntaminalian cells, ties been delayed until 1984. The short-term test based on the preferential induction of Cytochrome P448 will be intensively studied, mainly under contract, since recent work surZ;CsLs it may have utility in predicting the results of long term skin painting tests. @D Anicrican TobaTen Cu U4 1.16s muq not t-: cmrivd or shroun it, unambori%ce rcr%r"v% BAT Co LTD - MINNESOTA TOBACCO LITIGATION 2 4a. other short-term tests The method for measuring irritation. based on mucus secretion, is now developed and will be evaluated for sensitivity to cigarette design chanaes with a view to its use as a biolo-ical test. a 0 4b. Developnent of models for atherosclerosis All work in this area will be carried out under contract and within the year we hope to deter-nine whether or not the model will be useful in lookinr, at Lhe effects of smoke. An extension of the study, using humans -ind looking at acute and chronic effects of smoking on arterial function, will be accelerated. 4c. Scruin glycoproteins Clianres in serum glycoproteins in animals are being investigated since it is known that such changes occur in hiiiiians, possibly at an early stagc in the eevelopment of various discascq. During Lhe next year it should be entablished whether this area of research should be continued or abandoned. 4d. OLher tests Some further Contract resenrch Is likely whon requirements for tests for ndditivcs fell outside the range available uithin GR&DC. At present, worl. on Eugencil is scheduled to be completed by IaLe 1983- 5. Smokinp and regulation of enLLU _t;-Ia!!cc An external cortrnct has bcon placed to explore the role of nicotine in modifying the dcgrce of wcight loss/gain by smokers/ex-smokars. G.- Tests involvinn liumans Tinc study with Professor OppS will f inish during 1983/4, althourb the niih.-;tnntial anount of urine atinlyucs requircd mcnins thit final results will noL I)c available until 1984/5. Furthcr work in this area is unl ihely. Collaborative work wiLlt Dr. 11tgenbotham, Papworth, involving lung fkinction tasLs, will continue and will also involve studies into variations of smoke inhalation pattern with change of product. C=D C=) ---j V 19F@ 1t,it@A-Amcr..7::n1O1,3CCuC(,. UJ BATCo LTD MINNESOTATOBACCOLITIGATION