Tobacco Documents Online

-5- nutter£al8 to 30Z did not cause 8 £u=ther co~sietmst reduction in E:poeu~e Level fOE shy of the substitutes (FLKure 3). S~D~ DOS ~I~Y e Desp£te chaises in average smoke con~en:ration sad puff mmbe~ p:oduce~ by the i~troductlou of the substitutes, the level of TPN deposition ~ sequels was :el&ted to ~h8 product of the two factors. Heasu=ements of the deposition of pazt£culetes in an~nals exposed to smoke from both control and experimenttl cle~:et~es showed that TFH dose to the lover respirator7 system (LRS) tms closely co=related to E~osu~e Level (7£Kuze 4), ~thin the range of smDka concentrat£ons and exposure times used in this emper4,nent. The demonstzat£on of this simple =elat£onsh~p indicates ~t sdd£t£~ o£ the sheets 4£d not not4cetbly thanks T~M 4epos£tion cl~racte=£st£cs not, p=emmably, the ~:med~Ats response of aa~n~ls to smoke £:om 8n~ of the c~Se=ettes. ~ the u~n toz£c£ty study, me&sure.star of blood ca=boz~hemnoK%ob~n (COHb) levels in An~,SSlS |Jmnedlately following exposu:e to m~ke should a s~u~laz relAt~m~sh~p be~veen COHb level and ca:bon mono~Lds E:posu=e Level. Even more s~nply, blood COHb levels in animals ~trs s~8~Lficantly related to totsl CO deliver7 from c~Za~ettes, ms mssessed by 8 conv-nt~onal cbaL~cal Assay method (~able 2). BAT Co LTD - MINNF~SOTA TOBACCO LITIGATION SO

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-6- T~2 •OraL CO DXLrV~Z ~ cIca~r~s aND C0ab L~LS ~aLS ~OSZD" T0" r~o n~-~rzo.s' o~' ~o~ ~u~ ~asn CiKarette IOOZ TOB 17Z SC 17Z WC 17Z BK 30Z SC 30Z WC 30Z i • CO De Iivez7 (~,/e:LS) 13.2 15.7 15.6 13.6 18.1 15.9 12.7 i e i Correlation co~£ i~ient o£ CO deligezy/COBb Siluif icance Level TOXICOLOGY The raapo~Iss of l"mi~lla Tozicolo~ 1:7 1:11 30.1 26.6 33.1 29.1 33.0 26.2 26.8 23.6 41.6 33.8 38.& 29.6 30. & 22.9 0.88 O. 91 99Z 99Z Blood COHb (Z) el nosi~etr7 ii 1=7 28.0 31.5 30.8 25.7 31.3 27.9 23.5 0.80 95Z lzll 22.7 26.1 26.0 20.7 28.8 2A.1 18.1 0.92 99Z to mke £rom rJ~ vat-£ous c£Ka:ettaa vere :~ilaz i:o those seed in other to:L~colo~ atud£es. Growth rate og animals e~posed to smoke was less than that of sha~-smoke4 ~ case aou~rol ra~s. Rid ~11 numbers and ~k~ baamos).ob:Ln content o£ the blood o£ smoke-exposed rata vote hJLI;h~ than £u the ccmtrola. Presumably tb~a latter e~fect m a compensatory response to t~e pote=t~I reduction in oxysen cax-tT£n8 csp~c£cy o£ the blood due to ~he regular increase in the COBb levels in smoke-exposed rats. A small number of ~--~ls died during ~he at~ady. BAT Co LTD - MINNESOTA TOBACCO LITIGATION m ~o "--O

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-7- mout of the toxicologlcal obsarvacLons were crmmcment-~elated, 4~ the sense that they were more prev&1~t amongst m~Lmals subjected co smoke £roa cigareCr.es con~m~";'tZ one particular subsc~.cut:e. IiZSTOF£TBOLOG'Y The resp£racor7 sysc"~ of ~4,m, ls e=eposed 1~o smoke from 811 c£earect:es ac a common d£1uc£ou (1:7) leveZ was zr~m£ned in der.ail. • su~mx7 o£ the h~scopacholo$1cal fludLnae 4s liven 4~ Table 3, which Lucludls dup1~cmce 100Z tobacco ~oups. F~c each l~ZaneCe:, the response of tissue £r~ e~ch of the expe¢~c&l iproups £s shorn as a pewcem~aee of the snaz~nml IrrOUp mean =-.spouse ehou~ far Chat- pmrl:lcular parmCe:. An overall assessment of the dezz'ee of ehanee 4,, luns structure due Co mnoke exposure can be made for each of the creaCssmsc &,coups. TAm, Z 3 s~Y oy -tS"~p+~r'~LO~ Y~ND~GS. ZELATZV~ USPC~SZ FOR Pacmaec~c Desc~LpcLou ~tle Sham IOOZ lOOZ l?Z I?Z I?Z 30:[ 30Z Conc~ol Smoked ~ob4Lcco Tobacco SC WC BIt SC ~TC 1. ~crophaee acCiv£cy 23 27 88 81 100 77 73 77 77 73 2. Goblec cell dieCrib.cio. 26 35 95 g5 I00 86 86 100 81 71 3. Bronch£al 8oblat cell hyperpl~s£a 6 11 77 9& 100 81 58 77 77 66 Trachea 4. Ep£~heli~l ~h£¢knee8 (%e~ 78 78 87 91 96 78 91 96 83 83 traehea£ ring, vauCral)• • 5. Goblet eelZ bTperplasia 16 0 33 83 83 100 17 SO 67 16 (LS) (Upper Craahma) 6. Goblet ceil hyperplas£a (TS) (Mid L'tachea) 23 23 77 10o 8.5 69 77 38 8.5 56 7. Squamous metaplasL8 39 39 72 78 100 9A 83 100 89 78 (v~nC:a~ em:f ace) 8. Squsmous hyparplu/.a S& 54 83 88, 92 88 8.5 100 73 80 (vocal cord) g. ICerac/.u.£eac:Lou (vocal O 0 14 71 100 ~3 29 ~7 71 29 cord) • IOOZ Zxposu=e co 100~ ~L~]~ 1:5. BAT Co LTD - MINNESOTA TOBACCO LITIGATION k.,,,a

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-8- To assist the assessment o£ r.he various raise:ire respOU~es to smoke exposure from the d£fferent c£KarecCes, ~hose paCholo~ paruttrs ~t~ch are cons£dared co be most :eL4able /~ this study have been combined t~o a "sevexi~ :[j~ex" as sho~ ~ Table A. TA~LZ 4 A~ F&~ RESPOHSE (ZXC:LUD:~G OOmLET ~ Iff~RPL~ AWl) ~3:NZSATX0t4~) Group in AscendiJ~ Order of Sevezi~ CaKe control Sham-smoked 30Z BK 30Z k~ 17Z 3K 17Z Severity :L~dex 44 47 77 81 84 83 85 87 ms Less ,p Severe The respon~e of the eve fproups of an~JmLm exposed to IOOZ tobacco smoke was s~m~Ler. CigaxsCtes couts~ E and g[ produced t response which tsn~ed to be Less ~ that: for the LOOg tobacco cLS~sCta8. The severity of the :espouse reduced as the Level of substitute m&ter£a~ /ncreAsed. Me r~bLe also shows that st each LncZusion leveZ h~ Kwre a slightly greater response thau BE;. ]Seth groups of animals exposed to 8mohe from ¢£jarettes with SC shoved J distiuc=ly more severe pachoLo8~ response. However, for ~h£s pair of cigarettes the degree of clumse was pract£cAlly the salt for both £ncZueLon levels. BAT Co LTD - MINNESOTA TOBACCO LITIGATION m

-'t- o BAT Co LTD - MINNESOTA TOBACCO LITIGATION w

-9- Smoke F~poeu~e Level (£~om F£~e 3a) £8 used to try to account £~r absolute differ,nee, in PUff u.mber ,~i ~b averaKe smoke concent~atlon produced by equal dilution of smoke £rom dt£fe~ent cisarettee. Tak~ this expreeeion Lnto a~count the changes 4n smoka-~uced ltu~ pa~holo~ caused by exposure to mooke from tJ~ control and eheet-con~ai~0~ cigarettes az~e shown :i~ ¥iKtt~e 5. Overall, smoke from ciKareCte8 ~outa~n/~s SC, even at slightly redu=ed Exposure Levels, produc4Kl a Fearer response in the Itm8 than that £ro~ c£Sarette8 ¢o=~£~u~s ~ and ~ or 100Z tobacco. A re£/~ed averaKe patholoay index, based on par~ter8 1. 2. A. 7 and 8 and excludimg those psrmters ~soblec cell h~perpl~a) which ~re not well uudersCood or coa~idexed Co be of doubt£~Z v&lue Lu th/~ study (low Z £nc£dence of aXLI~sls wlCh ke~atln£satlon). ~re clearly isolates SC u the worst of the rJ~ee substitutes. CO~CLUSZO~S The study was complicated because o£ ma~ked cha~es in ciKaretce chmracter4st~cs iucroducod by the use o£ di£ferenc sheet m~terials and the relat£vel7 low i~clus£on lovelm o£ sheet ~ate~cials used. Neve~t:helee8, ~t 18 cons£dered chat the complete experiment (based on a balamced appraisal o£ dos~cry, tox£colo~y and pathololry) has been mucceme£ul in achlev£n~ the objective o~ eho~£n~ the relative tox~L~ o£ s~oke from c~$arettes couCa4~is~ St, WC and !~. Cisarectes conca/~n8 wc up .to the 30% inclus£ou l~ve~, deep£te hav/~ an /~cteased pu~£ nuabe=, caused ¢hanses in rat lu~S patholor~ vh~ch were 8~m~]La~ i.n deerae or sl~jht:ly 1tess then those produced by the 100% tobacco c£$arette. BAT Co LTD - MINNESOTA TOBACCO LITIGATION

BAT Co LTD - MINNESOTA TOBACCO LITIGATION