Tobacco Documents Online

°l i~ '94 15:45 ~-4.Q °"0:~ $03382 INBIFI] K,-,eln ~020 02S A'I'rORNEY WORK PRODUOT~ I N T ~ R - 0 F F I C E C 0 KK E S P 0 N D EN C Z To: .~. L. Spielbezg Dane: From: ,F. P, Gullotca, C, S, Hayes, B. R. MAruln Subject: .~hen Nicotine is not Nicotine SU~AKY PaC~ern-reversal evoked order ~o as~es~ the cen~3~l nervou~ ~ys~a~ ~CNS) effects p~oducad by the filler~ were overspr~yed wi~h e~ulmolar nicotine as either ~he ba~e (~) or s~rea~ nlcon~e delivery. were appro~i~a~iy half ~he magnitude of ~ho~e ob~ained wi~h FB and unex- ~rac~ed cigare~e~. ~e~e findings indlca~e ~ha~ fu~r~ CNS ~die~ shoul~ be conducted v~h F~ cl~ara~s, Dana obtained in the ~=el£minary ART scudy~ indicaued tha~ the smoking of a cigarette made t~ ~eri~ specifications resul~ed in CN$ effects gre~ter than ~ould have have been predle~e4, based upon p~evious studies. However, ~hese praviou~ studies employed cigarettes made from filler ~hat had been The da~a obtained with the low tar blend elba:erie in ~he preliminary ART s~udy led us to po~=ul~e that nieotin~ delivered f~om NC cigarettes m/gh: be less effectively transported or ~ansferred, possibly due to pH effects. Consequently, we conducted a study comparin~ CNS and subjective effect~ produced by ~he smoking of NC cigarettes t~ the effects produced by the smoklsg of cigarettes made from filler ~ha~ had been ovezsprayed ~ith equlmoiar amounts of nlco~ine as ~he base (FB cigarettes).

21, 12 94 1,5:46 ~-49 2203 3t)3362 INBIFO Koeln @021 025 Three hand-~ade cigarette types were tested. The cigarettes were prepared from the same batch of ~RT-extracted filler, using Meri~ blanks. Cigarette AE was made from filler over,prayed winh an euhanel vehicle only. Cigarette FB w~s oversprayed wi~h nlecnine as ~he base in an e~hanol vehicle. Cigarette NC was made fro= filler oversprayed ~i~h nicotine as the cltra~e in an ethanol vehicle. Target levels for bo~h cigarettes were 2.15% nicotine. For c~g~ettes FE and NO, 20% additional nicotine was ~praye/ un the filler ~ correct f~r possible !osse~ durin~ preparation. Seven cigarettes of each type were given to ~. Esperdy~ Using gas chromatographic ~echniq~es, E~perdy de,ermined that the fillers for ~hese cigarettes contained an average % nicotine of 0.08, 2.10 and 2~37 for ¢IgaretueS AE, FB and NC, re~pectlvely.~ The pH of these fillers was determined to be: AE, 5~8; FB, 6.4~ and NC, 5.2.$ ¥~ff x puff smoke analysis in the Cigarette Testing Services Division indicated chat cigarette ~B ~elivered 0,76 mg nicotine/cigarette for ~ puffs and cigarette NC delivered 0.70 mg nicotine~cigarette for 8 puffs. Smoke analysis of cigarette AE indlc~ed that no nlco~ine was de~ected. The puff X puff n~cotine dellve~y was very similar for cigarettes FB and NC~ h~wever, it Nu~ be n~ed ~hat these results are from a non-snandard analysis using fewer ~han the recommended numb~ of ci~areu~es.~ Twelve R&D smoke~s served as subjects for =he study. The~e twelve ~uhJac=s were a subset of the twenty who participated in the preliminary ART study. The mean tar and nicotine delivery of the cigarettes tha~ r~he subjects normally smoked was 8,62 (S.D, - 4.12) mg/~i~t, and 0,71 (S.D. 0.26) mg/clgt., respectively. The subjects were irm~uc~ed Co abstain from smoking for ~wo hours and from ingesting ca£felne for one hour prior ~o ~estln~. A doubie-blin~ procedure wa~ employee, where neither ~he subjects nor the experimenters weTe informed about which cigarette was being te~ted. A!l subjects smoked each cigarette using a con=rolled smoking proce- dure. The con~rolled smoking ~rocedure ~!nimi~es bo~h inter- and in~r~-

21,12 94 15:4[~ ~-49 2203 31336~ I.k'BIFO Eoeln ~I)22.'I.i25 subject variability with respect =o how =igarettes are smoked.~ In current study, the subjects were required =o take eight p~ffs (excluding l~h¢ing puff) on each cigarette. The inter-puff interval was held at .Pre- and post-smoking PREP~ were recorded from two scalp loci. One electrode was positioned over midllne occipital cortex (i~.~, Oz), while the second was positioned over mldline parietal Co=rex (~, Pz).~ The PREP waveform components that were measured were: Po, N~ P~ and N~ latencies and Po-N~, N~-P~ and P~-N= amplitudes. However, only P~ latency effects at 0 will be discussed in this mem~. The data were analyzed using ~ two-factor repeated measures analysis of variance (ABOVA)~ One ~actor an~ly'zed for ~he ~i~ference between pze- and pos~-smokin~ values~ while the second factor analyzed for the d~ere~¢es a~ong cigarettes. Followin~ ~he ~OVAs, the data were further analy~ed usln~ p_o~_=th~ ~l~iple ¢o~arisons te~t~. Additionally, a paired t-test those obtained with ~e low tar blend cigarette in ~e ?relimina~ ~T At the end of each experlmen=al session, suSJeets were =equlred complete a 5al~ot (seven point s¢aie) evalu~=in~ the cigarette that was smoked. "Mouth/throat impact" and "liking" s~ores were ~nalyzed Previous work? has demom~trated =hat the latency of,nhe P: component =f is smoked. ~n the current study, both cigarettes ~B and cigarette NC produced s=a~is~ica!ly si~nffieant post=smokin~ latency decreases. However, the magnitude of the latency decrease was not ~he same for both cigarettes. Cigarette FB produced a P~ latency decrease of ~.29 mace. Cigarette NC produced a P~ laue~cy decrease of i.II mace. The latency ~ between -3-

21,12 94 15:47 I ~P I FO l(,:~e in blend c~re~te produced a P~ latency decrease of 2.84 msec~ A paired t- ~es~ revealed ~ha~ th~ latency e~fects produced by the i~w tar blend .e~f~_~s ~hig~hvere~_o~arab~e.~o__~h~ unex~raetg~_~i~arett~. Subjectively, clgare~te FB wa~ perceived as having hi,her mo~th/throst impac~ (~ - 5.08 y~. 3,58) and was liked le~s (~ - 2.83 v~&~. ~.35) than cigarette NC.~ We postula:ed that ~h~s finding was ~e to ~he use Of the controlled smoking procedure. Controlled sm~klng does no~ permit the subjects to modify the ~anner in which they ~oke in response to changing £n .mourh/thzoa= impact (~ - 4.45 ~_.~. 3.~5). However, ~ smoking resulted in comparable llk£n~ scores for ~igare~es FB (~ - ~.00) and NC (~ - 3.82),~ Since flavor m~dification studies will employ I~ smoking, differential liking ~t~res tha~ were ob~alned usin~ the ~on~rolled proaedure will not be ~f c~nsequence. In s,~._ary, the resulta of ~h~ current s~udy demonstrate ~hat reties made from filler oversprayed with nicotine as the base (FB) produced CN$ effects comparable ~o cho~e ob~aine~ vi~h unextra~ted ci~are~es with simile~r mainstream nic~tlne deliveries. Ci~arette~ made from fille~ over- sD~ayed with nicotine as ~he citrate (NC) produce CNS &ffects which approx~etely half the magnitude of those oDtained with ~e FB or in~icate that we should conduct Phase ~ ~T s~udies using cigare~te~ fro~ filler ove~sprayed wi~h a nicotine as the -4-

i 4% C. A. ~.7~ 0.~3833 38.3333 2 2% C. a. 5.]0 0.03933 39.3333 3 t% C. ~. 5.30 0.03~00 3~.0000 $ CONTROL 5.80 0.03467 34.6667 5 I% KO~ 6.5C 0.03333 33.3333 6 2% KOH ?.05 0.03193 31.3333 7 4~ KOH 7.9~ 0.D2933 29.3333 8 8% KOH 8,BO 0.02593 25.3333 0 additive 9 %~T~ iN]C/PAD)/~PM 10 7.866~ 7.2000 6,9333 6.6667 6.266~ 5.0667 38.3333 39.3333 36.0000 34.6667 33,3333 31.3333 29.3333 25.3~33 11 TOTAL NZC 7.6667 7.8667 7,2~00 6.9333 6.6667 6.2667 5. 0667 5.0667 2,3~000~ 2.490000 1.936667 2.q20000 1.89000~ 2.00666~ 2.21000~ 2.3666.67 ~22,133333 125.q00000 '32.966667 :33.000000 ~1.20000~ 75,233333 " 126,05D000 1 4% C. A. 6.156522 0.057739 2 2% C- A. 6.330508 Q,06457~ 3 1% C, A, 5.37963~ 0.09!57~ 4 CONTSOL 6.980769 0.095~92 5 1% KOH 5.670000 O.lZl20O 7 4% ROB 7.53~091 0.256~77 2.30213 2.5[540 1.96963 2.45300 1.930~ 2.04787 2.28523 2.49272 0.929139 ]. 4)09780 1.6,73746 1.345291 2.092831 2.01:1850 3. 292151 5. 056732 m

Gul!o~=a, F, P., Hayes, C. S. and Mar~In, B. R. Completion of Pre!iml- nary A~T Study. Memo to H. L. Splelbe~g, i989, June I. 2. E~perdy, R, C. PM Notebook No. 8818, pp. 41 and 49-50. 3. Mar~in, B. R. PM NoteSook No. 8843, p. 14. 4. Martin, B. R. PM Notebook No. S843, pp. 6-10, Gul~ot=a, F. P, and Shultz, C, J. The effects of cigarette smoking on the elee==iCal act(vf=y ~ the human brain: Studies on ~he pattern rev~rzal evoked potential. Special Report NO. 82-097~ 1982, March 24. Federation. ~lce~oencephaio~raphy and Clinical Neurophys~o~o~y. 371-575, 1955, Gullotta, F. P. and Hayes, C. $. 1620 Annual Report logical Studies. Re~ort No. $a.165, 1984, June i. Eleetr~phys~- 8. Martin, B. R. Notebook 9. M~rtin, ~. R. Notebook J. L. Charles W. P. Hempfl~n& K. S. Houghton, R. D. Kinser 5. L. Myracle