Tobacco Documents Online

0oszlm, rr mmtpY: =os 'L'O ~ ~-,,.,~ ~ D~A.-,~,/m,r~ C'P.GI,,IIaI,-+,P.S 10.9.1979 AUT1EDIIS: W.G.D. LullCOn G.A. ]ima.d IS~ ,,l'g: C.Z. JL~rtes Z~.OG. ]LET. : 11.03.04 DZSTJI.Z]K/t'ZOIh Dr. 8.J. Oz'eea COlRt io. 1 Dr. II.A. 114mtorcl " " 2 1.1. G£bk, Iml. " " 3 1.8. Ikl4m, rdlq. " " 4, 5, 6 I.G. lLc:bo11110 lllq. " " 7, 8 Iharlr g. I~ggmgmbatm . n 9 Dg. Y. Ileehofeg " " 10 lye. G.J,P. de S~queJ.ta " " 11 l)r. D.G, ]Pall:on" " 12 I,:l.bz'ary " '° 13, 14 CO Pt' m0.: w 1..,"1 m ,,.mi. 8 a, [ Co LTD - MINNESOTA TOBACCO LITIGATION

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~X~L I r~AZ /CALI ~D Group Kele&rch & Developmlut Centre, Bz-Atish-Amlrlcan Tobacco Co. Ltd., IO~h 5epCembec 1979. DO|'nm'ruT froDYs ~,?,~ "rm~._ TL~ ,DO a~A TO stAq"S FItOLq (Import llm. ED.1599 l~scr£cted) One possible approaeh to ~ assessment of ~e b£oloKical response ~0 stooge part£culates is to apply equal doses of TPN Co the lunKs of • ~iJals e~oed Co ~e fz=m dAffereuc ¢lSaz~Cteo. A study vas carried 3ut to 4etez~ how accv:ate such aa~b4~ of dose ~evelo could be. K:cscc mmCcbAa4 of TI~ dose Co Cbe lunlis of an/Jals was achie~td in 80m8 but ~: 4n all firoups of antgals exposed co mm~. The t~herent waxiabllLty of dosiull In inhalation experJJsuts ~Ch rodents Ls similar c~ Chat NOn in similar studies with ocher species, including man. ~ivan tJ~s limitatLon, and • Koo4 knevledse of the pz~cis£on with vhich required dos£n8 can be achAeve4, coupara~Lve s~dAes on smoke a:e possible. For any work of tJLLs L~Tpe, doei~atry H~l~OmIDt8 are emmlml~al fe~ proper interpretation of CMe b£o~osicsl data. I%~ Zo LTD - MINNESOTA TOBACCO LITIGATION m

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-2- INTIODUCT[OH PravLous studies ot acute £n/~lJtt~n to~4coZofry reported from these l al)olr&corLes have ben ~tn£~L out on • "per ciKmz~t:tt" buil, often ustJS$ c:Llimrm~tes with di£ftrent puff slumbers or ~ deliver:Lea (1, 2). ~o it:tempt I~s ha made to pbTs£cally compmmm~e for thee differences slthouGh 4-terpcetAC4ms of ~o~LcoloKy studies has taken them iuto s~ount (3). For many purposes, 8n 8ttempt to eompm :elet£ve to~c£t7 of mob L~am dLfferent cLeazettes maytbe of L~tetost; for role, ia comp&r~LtqB ci8~t~tte8 v~th 8:]Ls~lsr TTH delive:tes ~hieved by d£F£ereut umthods of f£1tration or veac£1ar.ioa. TiLts ezperLm~ m d~siKnad co de~ent~ how closely the :retaKe dose of TI~ deposited in Ube respirJtOZ7 rTstA~ of rats could be matched u4~n ~Lserette~ of different deliverLes ~tre used. & vLder range of TFH delivet-les (amd, therefore, of eke d£1ut~on~) than would probably be ~ecessaz7 in • toxicoloKy study was mloyed. m wDs Three c~eAt~tte types q~re made usiJSK a tm84c 6~ m rod of Bland ~8 tobacco, wrapped in h/.Kh poros4t7 ps~tr (Coda 95F, petue~b41£t~ 80 COR/iST~ un~Lt8), mad fitted qrJLth one of t]Lt~ nost-s~rd f~ttets. Tb~ fil~8 vere deaLKuod from c81cuLetlon~ performed acco~din8 to d~t~ Lu the tLSmtte OeeLp Handbook (4). The most ~poz~nt spucL~et~ou~ of the fLltors, the ~Karott8 dellv~t~es and som~ d~ta s el~tf~8 to c~4~mttes ~n~o~tod ~th the T~ Cr~cer, decacJ~lorob£phe~TL (DCSP), are iive~ in Table 1. ~lthouKh the T~K del£vez7 ft~m these clKmm8 vm~Lod by • fa~cor o~ mrs ~b~ ~b~e~, the delivery of carbon m~ z~naJJ~d relatively c~net~zt u~q this approach to ciisrette f ~u~en. L~ r~ r~ r~ 8 ~, [ Co LTD - MINNESOTA TOBACCO LITIGATION

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-3- Touns (175 S) male race "(giscsr, CFHB strain) ware suppZLed by a c~ercLsl breeder. "After quarsn:£~, animals were randoa~sed inco elKht Kz~ups of tan rate each, and accliamtised to smoke over a period ~f saree days. Two Stoups of ten rats each wce exposed co smoke from the low TPH clssretCe ~lgO) at a mnokm 4Llut~m of 1:5, rhine a further ~ Stoups ~f animals received emoko frou tho smd:Lun de1£vet7 cismrette (Y~8g) tuS~lB s 4£1utlen of lzlO. SL~LI~,'IT, the hJ.sh TI~ del£vor7 c£Serecte ir~88) ~s used to ezpoen tuo groups of rar~ at L:I5 smol~ dilution. linder these em~lt4ous, all Kroups of ~4msZs ware exposed to nominally equivalent ~b~r ,-,~,.M~,~trat4tm. ........ of TFN from ehm ~h~ee ciEarettes. addition, Cuo Kroups of rats 1ere emposed to smoke from cigarettes E188 and E190 z~tspect~vely, both at lslO smoke dilution. Equlvelenc dilutLon of moke frum dLifferut c~Saxettas Save 8 ranks of chamber T/~ ccmcmtrstJ~ns in p rgpoz~ion to the T~K deliveries of c£Sarettes I Table 2). Tam enperims:t8! desisn is sbo~ in FLSure 1. dkfCer accl4mmttent~, each I~roup of rats was Siren two days of ~¢~Lcm d~L17 ezposuzo co smoke under r~bm ~ppz~pz~sca conditions, before ~ecelv~u8 the final dosinmtry exposure on the third day. T~ediacely dear exposure rats more k~l~ed with KuChar~l and blood rumples were ~'~ke~ for measurement of csrbozThumo81obi= level usLns the method of ~'cm~8 and Leaker (5). T4ssu~s were removed, um£8~nd and deep frozen ~muii~g malysis for DG~P. N~~ of chamber content=sCion of particulate8 f~om each of the f ~h=ee test cisaretces produced very si~Llar ss~ke emposu=e levels for m u B a,! Co LTD - MINNESOTA TOBACCO LITIGATION

INDEX HAS INDICATED GAP IN BATES RANGE HERE

-4- replicate individual S~'oups (I v. 2, 3 v. &, $ v. 6) and for pairs Of grOUpS (I/2 V. 3/4 V. 5/6). The af£a~t of d£ffereut£al dilution of ask8 /~ clearly shown by the graded concentration of ~e~ carbon :~aoxlda 3.eva1 to which r~m various groups were exposed (Table 2). The mean mwunt of par:iculate --tier depos£ted at each slte in the respLratory system altar exposu:~ ~o equal TPN connan~rar~Lons from each of the eZlX~tmsntal c£sarattes Is sboun ~n Table 3. Ths=8 were no sisu£ficant d~fferencss in ~ke ammmt of TPt/ dapos/~ed in the lumSs of repl£car~ Kroup8 of animals exposed to 8m~kl from uch of tha ciKarattes (1 v. 2, v. h, 5 v. 6). I/san blood cazboxyhaamoglobln levels in these pAirS O£ groups wars also very SiSLLlaZ (Table 3). The pa~rad values ransed from ~SZ to 42: COKb &pproz/mattLy, reflec~LnS the marked differences £n ~:arbon monoxide conc~atration (Fi~s 4). Desptta any differences in the exposure co:~L~tlons used in this part of rJae study, the relative d£str£but£ma of paz1:iculatas daposlted vithln the rupLrstory systen =mined pract£cally ~hs sam. 0verall, $5Z of TIM ~s deposir~d in the lun6s and £nd£TLdual pups shewed L~ttla s~ur~atlon from this man Crabla ~). Th~ raplicab£1icy 0£ d~sLn4 for /z~d~v~dual ct~srettss was conf~tmad by analys~s of dosLmat~y ,data for lunSS when expressed t~ te~ms o£ TPN depostted/K of lung :~ssue Ctab].s 5). ~meve~. tha purpose of eh~Ls pat~ of the study was co deter~i.na whether equal dosiq of TIM cou£d be achieved by exposing a~Lma~s to equal coneentratLons of smoke from different elgarattas. PooLed data in Tabla 6 ~a8 analysed by llmmans-Eauls Test for campsrl~J Stoup u~ms. Jumlys4s of YP~ dar~ of pooled groups ((1 + 2) v (3 ~) v (5 ~6)) sho~ed chat ~here ve~e sisa£fican~ differences in Tlq5 C~ B ~ I Co LTD - MINNESOTA TOBACCO LITIGATION

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