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t HK0429064 ht .ar 1568 I essra. Orautp Haa8 Hetsko. I ms, hltbm Teasan e ard r. ltQhert 0. Boclc t

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22 Apr 1998

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t HK0429064 ht~.ar~ ~, 1568 I ~essra. Orautp Haa8~ Hetsko. I~ms, hltbm Teasan e~ ~ard~r. ltQhert 0. Boclc~t ]~elaeed berevlth t8 a cq~/of the Summary Report ~ the Peelf~e ]ee~hwst ~orttorieJ ©f the )~ttelle ~riai Institute of" Ri~Lm'~l. VaahL~tonp anUtled The ~eeeu.re=~ent e.~ Cf~ar~ttu.Szoke Deposited in Do~e t~ • ~et~ Blaulatfn~ E~'~. Snokln.~. This iS the t"~w.L ~'~pm't on ~ho ptcrtictLta~ 5the effort vH succese~ to • reasonable de~ee, but extensions vLLt be ~ecaasa~r for ~-osaible develolnmnt o~ • t~ vork~bl~ ~hod ~or h~an% do~ and =ice or other S:LLI animals as o~cliued belcr~. - The re•hod used For ~okln$ doJut IS rather einut~ly described. Zt il.~-~te d~F~e~ent ~roa tlw methods ~sed in moki~ ~ee, ~a the lttter~ the s/wke is ]~r~duced by entirely mechc~dce.t ~an~ so that the eondltionm e~n ~e Jzade ~o e~ ~'~'~-~ c~osely to ~ co~ventionLl standard that is b~/~d on hues• pea••lee -- ~ sc~, p'~er :t t~o seconds d~retion t•~en cn=e s e~nute, T~e snake so paddled is then delivered to the Lice at the Fight a~e end deKre# of deletion 80 tbst it ¢~n ~e lr~&led by the Lni~a~8 et t,~clr o~ breathin~ rate /*or a= ~a~" s~co~d8 a~ m~¥ he desired. ~'~ the ~attelln 4evice, ho~ver, the dc~ ~roducee Its o~n s~ctinn for l~J~lr~ the ele~rett~, But e~nee ~he emokLn~ ~cbanLca e,~ t~ dn~ nee ~ct like thole of a }n~an. some r.deptetion has tG be re:de to obtain s~J~-~Zar con~ltL:~a. A men is ssld to pU~ tbottt ~ ml, oF seeks into hie ~ou~h ~ then to inhale this alon~ ~th oft into b'.~ lug. ~ evera£¢ tidal w~l~.~ fo~ (vol~ o~ air Inhaled in ~ breoth iP, ordin~T~ ~rsethin;) ~.t ~ulnusly ~%wn as 3~0 s~, t~ 'SO0 ~1, (O~ course it varies ~rcm p~rsor, to person, ) Battel/e u-era the letter r/gu~, ~ this basis tim ~:t~nderd I~oke ~ v~lt--- 18 ~'~ o~ t~ ttd~J vol~e ~) and the sooke 1~ dll~lted £~ t~es ~t air. T~ d~ does ~ot ~ lnt~ his z~th ~ then ~h~; he ~ust lr~h~es, I~ence the ~lutLon ~'as nrr~n~ed ~eeha~/et-lLy by the battelle tern. ~en the ~sl~w opsnod to ellc~ |r~sle',lsn o~ c~oko t}u.o~h the elsarette, T to 10 ml, were Ltlo~ed to enter, TI'ien s ~re~stu'~ transducer turned oF~ t~e ~ and s~loved fresh ~ir t~ ever tcr t,h~ rest or that breath, The tids£ vol~ne ~or these ~'d~orn-si~ ]~ecle 8~Gs is ~iVon ~¥ ~atteLtr as 200 =1. Xeric• ~or these d0Gs the ratJo o~ ~r ~itu~e to rid'" volt~ VrS ~7 to ~ SO that the smoke v~ k~JJ • dll~ted frca ~0 to ~,$ times ~lth elf, T~e dp~s therefore received a ~or~ dilute s~k~ th~n is prtsnr-ed to be u~u.~. ~'lth n'u'~. '~ ~pUL~" dttre~,ion v~ not ~eccrded ~u~ s~s: huve hee~ lel~ th.~n ~'.~ s~S, q~ 3uff Ir.terv~l mu~t b~ve 1~con ~t fifteen seconds. (;~hot~.,.,r e}~n~e~l ~/*£ect= these el~n~ta in l~fF eonditior~ ~r¢ introduce ~or¢ thereEerc ~re~er.:.) Q
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t~ . " e, • I *e |'o ". | =- I I q ! I ] I ,.o -I- HK0429065 ktte~lo eonsLders that trLth L~ nor~U, hu~n breathln5 ratax or 16 • mLlmt~ (~K~O mZ. esch breath), • ~n :lL~wl~n nigh(; libra oL" ~Lr e~h ~lnute ~tll theH l~azlea tr~ale about 20 to L~ tiros • minute (200 ml. o~h broa~) ~ 5 k i/tore Of air per ml~alte. :It • iwa takes one )5 el. po~ ~cr I~n~e ¢n • aip:et~e, that ~rllL be one ~iT per sixteen Luh~.atLons e;. 35 xl. ef eaok~ £~- nscb 8,C¢q -I. ~" total air dvrt~ t~ ~ period, ~attelle ~te.~o ~lvo ~he ~s • 7 ~. ~ tvsry ~i~h :,l~h breath : four ~r ~bls ~ou~bt the total ~nohe to ~ x 7 " ~ ~. per a/nut~ ~s, ~ho th~tie-~ man r,~lvts ~ el. ¢~ eke for each 8~0 ~. of sir vbLte m.o)d~ st I ]~u't ~r ~tnute~ the do~ received 28 ~1. of ~ ~ each ~,k00 ~L. Of air vhlle ~x~lr~ tt ~ ]),It par ~tnu~ -. • ¢onsL4erubly bflZer (thot~h st • ~ater d/lut£o~ vhen ~/~led). On • Ipod~ wlr.ht hanls~ ~fderLl~ the ~an to ~t6h I~O pounds to ~ pounds for the ~, the l~r mdm~te d0~o ~o the do~ was ~ ~ times •s ~r~at as £or me. Yl~s the d~• rec~l~ sm~ ~r ~lmte but at • ~ater d~utl~ tr/tb air. Acno~n~ to ~ ~s. it vould ha closer to hum~ practice to let t~e do8 drwl~ J~L, Or make before euttin~ of£ the v-~ve and 2ettin~ air enter £f t~ds e~n bs done vtthout e~ieatio~s •ueh U e~3k~Jl~. Then th~ dLLutlon rate ~ul~ be 1~ ~blch £s equ/£ ~o t~ ~ tar man. ZE this yore l~Ttated At every nint.___~h lnhe.~stion durlr~ the ~sokln~ ~er~od (~- tL~ea per ~ute), the dose v~td ~e the sa~...~e £or sum end do~, disreae.~dir~ ~tlaht 4Lif~ereuce. Tea" • close dosage eo~-~WSl~mdence on weiBht banis~ the do~ tbo~ld ~,eeiwe one ~ only ever/~ Lutu~tsti~ t~at ts~ I ~uLT each 2~ ~nUteS • ,BimJJ~ ealculstio~ can be alde o~ the basis o~ relative lttn~ t~eit~cs fur ~an vs. dc~ or of ~eLat~e lone s~rfaee~ relative bas~ aerobe|is ~t~, etc. TI~ ".election o~ "equivaLent" cond/tions v~L be 8~rbltrr.~ ~ ~'11]. depend larse13 upOa t~e nature o~ the observatl0r~ t~ be made ~u an~ p~rticul~ ~pzrlment. For • study to observe a~y ~ossibl~ a~p~ysematou~ chants in de~n~ ~t w~Td ~ee~ to ~e I081CLt ~0 mske the smoke to air ratio Lu t~e pure •s e~o~e u l~sJble ~ t~t lh~u~ht to be encountered by man but ~o kzep t~ total ds~]¥ do4e~e to the dog r•lntivelF high on the basis o£ relative ltu~ •m'~see. Since ~ys~m dsvelo~s el~v~y in ~l~ne 1;;}~ chronic e~er~ente m~s~ either be quote conCJnued or doseges made hear/st tl~n in normal In~zn ex~r£en¢o. ~deaUy, • maser ~t" sbn~t~eo~s chronic e~sr~nts sh~td be x~ade at sew~r~l dlrF©rent 4~e levels and at dt~erent a=oke-a~r ratios. The 2~ttelle re;~r~ recounts quJt~ clearly thalr experience in ' &~tta~lnG to dc~? a ~eLr~w~eet ~or tctuLL ~8 e~q~iul~e to S~OP, e. The tq~lr~ oF p~tar~Lum and sodium nst~LL1~ present in tobacco v~s not very Iwlprul b4eause &~h ~e~.t pr~rtic~s o~ these elements ace ~ran~C•rrad into the Ir, O~.e, t~x~ectedly tL~ed bromine proved ~O be • rel•t.ivsl~ pronl•ln3 me~]:er since the I~ a~d blood e~ntent of t~d hrc~lue i~r~asad directS7 i• ~ro~ti~n to the refer or cigarettes r~zo~d by ~ do(; under constant conditions. ~re are •C~ dlsadv~nteaes in ta~l:Ir~ ~hole el~aretteS by ~utro~ b~ar~c~nt. ~ have to re=sin • rat~lr lor~ tL~ in the •cttvator in ~rder t~ pick up ss~ou~h ~ and tend to dry out. A].SO, ©I" course, ta~i~ aa lndfserici~:mt. Blnce It ~ al~sars that vs ~nt the t~ er,~ In b~ine) It ~u.~d ~r~hly he better to ~dd t~ dellved ~t oL" ta~ s~dium hrc~de to the rebecca prior to" fabr~cstlor~ Into eicarettes, 1/' it e~n be distributed unlror~ly enough. AS=o, o.e course, ve do not kno~ hey ~ener~ll~ br~id~ Is ~rnsent Lfl clGerottes~ or st ~hat 2eYtls. l>rc¢~ncbl~ it •~ ~e derive~ in tr~ces f~roa us= o~ ~onm ~lCsnt such ~s
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P 6~ t ,i o~ t -3- HK042g066 But lnce~atinn of tes~,d s0d£~ b~a~4e ~ ne~e ~oeaib~ t~ control of tin tq as desired. ~e t~L emmet of P&d~o•ctlvtL~¥ CGq/J~ t~• ~} controlled earetully, The ~atte~te s~•tL' bel~tv8 that It n~ht be l~r~amlble trader AEC Fe4W,l.tt|Ouz 4;o bare such b~edr~-ta~e4 cl4~tJ~etbU smoked czl~rf~entaiJ~ • by bt~n 8ubJce~ under conta~Ue4 coeditio•J, PF Whole bod~ redS&tin• cotmt|~ and bloQd an~Wslc, £t ehottl4 then ~ p0s•ible to determine dnet hay ~u~h t~4 ~cu~ ia l~.ck~ t~ l• •orm~ "mmM mk.tn~ 8o that a direct co,w.~,erLeo• ¢o~14 . wL~h the alcoa. (The in~ ot ~ote3. bl~d brazine Coun~ In the 8mokl~ do~s is ~/~/tes~ ~ ~t it can be moa~ accurately boceuze •F Sts t~J~loectiYity. ) V~ d~d •or ask the BattLes pt~l~ oriK~J~ t;o •~t • distll~On between the total taZ Ln ~ and the Fr•ction thereof cta~ried respectiw/y by ~he 8u ~hase ~d bhe p:=tieula~a p~t~. Z~ •c~aed ~et to EIw~ ~h~ t~lr t~4 in the L~lt~t ~k. Ho~averp for 8ppliestLon to souse stud/es ~ £or ether ~:~u'j~osc|~ it ~o~ kc~ea ~tant to FS~q ~t ~ taf~ed ~Fun~ne 1~ dl|tributt~ betvse• 8se'rePor Fhase and the pcrticulatoc# as separated by & CtmbrLd~0 filter. ~e b~rve ~Jked )nit•lie to cake plans end eetisua~e8 for • brief' fol.l.O~ot~p st~ /;hat ~t~d luyolwt 8mo/ci~ te~ed cigarettes an • standard aaoki~ ~chlne~ determin~ t~JGed br~tne in the vbole sza£nst~eam amoke, passi1~ such ~oke thrc~h • Ce~bridGe Filter and deterxinin~ tt~ed broaine in the trapped particular•so ~ dlf'ference~ the l~r~ort.ion C~ bramine 4n the ~as phcse c~n be deter~ined~ or ~b~bl~ th~• can ale0 be trapped and ~eamured direet/~y, I~ there J[o • si~ffte~at proportion of t~td bromine in the sae-vepor l~hase, dc~ slwsdA be subjected to. 1~haletio• oL" C~mbri~Ke-filtcred e~okt From ci~a~t~ee eont~inLr~ the tt~ed br~4ne~ to cheek thel~ l~ick~ oF t~ by lur~ an~ blood frc~ K~s-~ap~r ]ph~e. Ve haw also uhe~ Battelle in this first re~attve~ brief Follo~.up 8tudF to co,sider deternLnir~ the chs~cs ~• blo~d cerbo• monoxide ~hab occur In these do~s d~rit~ clst~ette s~inl~ as another wtss~.• of Su-v~p~r ~hese contact v~th the Zun~. Since ve have san l~gures £or h~an resp~am, this vlLt pre~'lde a se~o~ buis Fc~r ~r~-d~ cc~'4~so~lam. ZF the results look ~n~a~q, t~d £F ~ sat~ef•ct~7 dirts• ~or o~posin4~ ~lee and hamsters hu meantime bee• developed, ve chosdd consider settl~ one o~" these ~achines st ~att~e. ~¢e e~1.4 Shed b4 sub~c¢t~d to Sn.~iotioh OF brc~ne-te~ed c~garette a~ke~ either ~ho~e or Cambrld~e-~/ltered~ ~or Co~par/son of their lur~ and blood p~ckup oF ~ ~ith t~at OF ~ ted AO~. Blood carbon no•could• determinations -4KhQ be m~de ccncm'rentl~ U • separate check on eel-phase contact. The rtlat~ve pickvp bZ open-~ee ~ seoled-r~e ~tce could be eclatS. It • suitable 8y~te~ •f ~ doee-~ou~tor~n~ e~arKea from these |n/tis£ • ,tue~oa~ the Battelle ste;rF m interested ~• eu~ittl~ ~ltns for locc-r~o studies oF s~e ~ t~ eFFects or ~ack of e~Fects oF ¢hro~c lnh.~etiOn by does OF ~mle, Fre~h~ nc=n~l" cigarette ~ ~der cce~d/tlona closely I~ac~blinG those er~ottnf~z~e4 by ma~ or dif~r£~ ~ these cond£~lc~J ~ • ~ de~l~ee. I :z ~.~,X.

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