46D i G 69 POSITION PAPER REDUCTION OF SMOKE NOXA 'NTPODUCTION Examination of any list of substances considered to be n,~xlous. agents in tobacco smoke (Table 1) reveals that their likely soL;rces in the substrate are diverse. Views may vary%on the need to remove individual items in this list. whilst at the same time the priorities a-.tached to them could depend on short-term commercial sensitiv,,ties as much as on scientific logic. Therefore, if for no other reasor, lor new initiatives towards their reduction to be of practical advantage, they should seek to offer substantial reductions in individual components, or across the board reductions in numbers of them. Sources in tot~acco of the so-called noxa range from those where ~ne substance transfers. direct to the smoke, e.g. metals such as cadmium and Polonium, through major defined sources of smoke components on combustion, e.g. ni-.rate giving rise to NOx and volatile nitrcsamines, to the many assumed tD have multiple origins, the relative imP.,,--.an:e of which individually remains uncertain (see Table 2). it is against this background that we have discussed app-oaches to research on their reduction in mainstream smoke, and the re:o'..'rielaations inade regarding projec~_s. Our brief at this stage did not include product constrai-:s such as immediate commercial feasibility or subjective consequences, all--hough we realise that these would ultimately need to be integrated 'r~-_o a,~v successful cutcoms. "'Scussior" U Potential Straoeoies The iollowing routes by which modijication right be achievet nave been considered and are discussed briefly in turn: a) Tobacco growing and curing, including variety selc----io-, b) Pre~ursor removal C) Combustion modification d) Tobacco fractionation e) F i I t rat i on a) Tobacco Growing and Curing :'~Olorations have been made, both within and outs4cz- the Group, of the options available for smoke componer,-. control via this route. Useful results have been achieved for some isolated components: -it-b CD CD 00 CD -11; cm BATCo'docurnent for Legal Services : Health Canada 21 October 1999 , I *:J, ano ni:-c---;7,inP-G Vla ferzili---2- zc;r-rol and .,ariety seie:--on ~Lurley and cu-- -:g mo" fication r9i - -: a i ) ',:s e of ni c- n~ --ot i -!.? vari e-, i es --, 4 n Pro-rata recuc-tions i- ---moke constituents --- constant nicotine :e I i very. UnsL::essf-j1 aztem.:--s neen made :o tnfluence CO -by cu .--r a c-. i ce Fur:'-er work in zniz area has been discoun-ted from consideration at stace because the tenelits so far icent*~ied have beer -.oo ';,i.-ftited to seek -.o control farm va r4at,eS on the large scale required. In :re longer term, 4'. is an area of po:ential, particularly thrc~:g,) the medium :;- advanced variety development. To do this specific inzrr-.--.icn on sources of ioxa will be reeu4-ed. A summ.lrv has oeen made in 7-=ole 3 of current of means of control via this route. Precursor Removal i ne ma,4or onzacle -.,, th~s rei-iiains the ",4;,,mited number of cl~-ar cargets curre,;--Iy available. removal has been developed by sc;me companies, parti:ularly for application Jily delivery of ox-,'aes ol nitrogen. to :)urley ste!n to mo, On present infjorma:4--n, this approach r-amains limited to cdifying smoke nitrogen compounds and, 'possioly, Ames requires , rl arer understanding ac--",v-.'tv. Ex~ensior --o others ea of --'-e tobacco Prec~;-sors involved. ;c) ConDiust.-Ion -Modiflica:4on Ocr-nustien :aechanis ' 7,z are 3bvlously rel,---vanz -.o the forna-.ion 0 numcer C7 the z.-.1.oke compounds of ocssicle interest, so -icazion are app,-oac.ies to --.eir zontrol or mod. i ir.0 :-ta rt . "n pra:`ce, two broad areas ~ave been studied, but -,~enerally in isclation: i) 711he physical ~--rm of the tobacco, such as strand sizee, particle form, and cigarette dimensions; and il;, 7hee use of acc'tives applied ei:ner to tbe tobacco or paper - oxidan--s, retardants, rnoc~jziers, and also in stucie~s of r-~:~nstitui4on such as ,he --.)rospecz;-- 'Dr s3;-.ie of thase app-oaches nay ,:)Pc2r bc-.h ~;ncert-m'-! and oaunzino. Iic.,wever, there is a cas-a for exa:~-,inina -.7-a infor-ma~-ion anc r,-risiderirg its The ~-arller l4e as 'Deen well surveyed i::! ~'-ti~ations. t . - rature ~i I ? , -rz R -' ' 2 M ~ a - viould seem t4:~ely :o update this out ':~ n --':,e curren: C:) CD C0 C0 -Nj CX) --4 co BATCo document for Legal Services : Health Canada 21 October 1999 As a guide zo Lne of subs:_~-:es .i-.h a h4story of use as substantial- Table -: -s:s those --ermitted in t UK a E 3 '. o r 7*"~;s cemc,~sz-%-_es some z-.versity of ne _hose which have rathe- Simply _!,~;Dmittet to research study. (d) -,cl)acco Fractior:!-:on Ext-action of tc-~_-::o Deen -2x-tens-'vely with particular refer-r:e tc processes and early attemQts at reduz'ng tre jiolog-4--a! activ`.ty Gf condensate. Tne reverse of Ln~s nas --'-so bee-. applied, in enceavours to isolate Ilavour Compreherisive o- --onaccc -:-!c:ionation ~- C ave been rare and the le,--2,_,3rted appear to h.,ve had limited obiect4ves (e.~. -,naz ~~V Bush or :!r zont,"but'on and by go So~kelman direc:~-_ to c2111; wall ~-!z-_Ions). Apart from 'he PR 1, . I -Y U program.-.-.--, in-~_-use effo- includes the C lproc process whicn dizz some s-~"ez-_'ve change of smoke de-i4very. A recurring ther.-= ~n ccns4;oeri-%c ---e or-ner approaches 'rlas been the limited ~,-.~orma~_4on on s_-~;rces of the noxa of interest. Tobacz-- fraczicnaticn the opportunity not oniv to find possst.~Ie -ovtes to with reduced levels of noxa, but alsc to prc,.-de tihe --asi: information required lor knowlecqe-ba-za.~ efficrt via c--*-e- rou-.es. An sxample ol a fractiora-_`--n scheme is as follows. ~ssume tobacco -_:~ ::~-ovize three zzszinct ejemer.-.s: Sources o~ ~n 3moke rarrier ~Neqazive Cz--ents ihe Iractionation wcuid z)e aimec -2: cotimising their separation in orzer to increaasz- z.-s of 4) -:o -IiiI, 0 ard to maximise tre use of ii). 7 .he argument advanzed here is at tne simplest lievel, but - . ne advantage o-. :ne approach is :nat it allows a diversity of thought to fts ~;no,le7.entat'0:_, a variety of technologies cculd be brought -.o oear on -Impr~r."n~ the separations and modifying the Iwo scnemes to invest4gate this sub,ect are presen:ed in the Accen-"x. (e) Filt,ration %.-.-erous efforts -;e ~een ma- reduc-~ion of specilic smoke cc-~;.anents hy and somp- successes have been recor~:-2:. On -resen: evztence, it is unlikely tnat this -=Pproa_-- :oul".- be~ use: -.L j:)tan ma4or reductions C) in sevprai his is .)ased simply 00 03 --4 co __Ij 1.0 BATCo document for Legal Services : Health Canada 21 October 1999 o rt 7: 7~ E! v ew t h a t z r o f, i P. e c a s ; i s w c u I (i b e --C ald the c~ combininc tner. into a s n q I t a r t,., o u DesP----~- --his negaz~ v~ _t-_:: sa' , the ro' a of :he fi I ter ,aill. o:)-viously rema4, a- -.na n1chest sis-nifi--ance and the pr : may need to be exo1tored again. ossi:;-'k`1ty remains -_na- ~ One ss:anario woulc be. sz~::_ess i- reducing x componen-.-s by ancther route allowin.: --ne oppor-.unity to develop a selective ii! _er -.o complet-A -,,-.a with regard possibly to a -emaining compound of -~ :c:,!:_-nce. A nodif-led form of :ne f`.*--ra-zlon approach has also been proposed - zhe use of :ornoounas added to the tobacco to act as scav'engers of the s,,.;t.,s-_ances being florried and transierred to smokz- The prospec--s 7or success via this route at CONCLUSION'S preserr~ ramain un~nown. Philosop~,.4r_ally, it is -.a d-,vide tne approaches to noxa reducc--ion into tt~.-.-o groups: 1. and 2. owl a-. 3 e- b a s ad At present imost strateg4es woulli~ have z-o be def'ned as empir , ical as we lack the 'Knowledge to develop 1 -supported and rational schemes for the reductior of smoke conponen~s on a selective Iles-is. It therefore seems appropriate that, in tryin~ . z. ::o -nake progress, it should be done in such a way the, the information Qenarated will be useful in understandirg the problem that is ~*inq tac,.,led and will allow the ;foundations to be laid flor struc-_~;re:: attempts to produce ?nd or even 3rd geierazicips of smoking prod,,;c-.s, We ~ecomrnend that the projeczs should De considered which, vinilst different in scopie, have nentary features: To evaluate current ootions for combuszion modification The first stage would be -.o L;ndertake a literature review paying particular attention to the , prospects for combining approaches which individually have hac iiinized success, and which might have possibilities- of synergy. 7he proce~ures and materials identified would then be evaluated. 9. To fractionate tobacco in orcer to de~ine the contribution to noxa from di 1-ferent sources ana zo achieve triel r seDararion Two approaches to this i-aave oeen set in the Appendix. "A" oi-nprises a general scheme wi-ich, woul J* C ... .11 . :u not only identify sources of noxa, tut %-iould also pote!izial approaches vi! genetic 4 C:) im,provernent and combust4 on. moci - I cat`cn. "B" is more limited an! sets out to achieve 5 ni;mber of components. CD cc cc co CC) CD BAT-Co document for Legal Services : Health Canada 21 October 199 Beyond this, ii-, is envisaged zna: --nis programme would also help ,o define the fu-.ure desirable :=:)inations of tobacz-o - identical or rela--ed mia-.erials. for 2-nd generation smoking products. An example of the Satter :an be pro--csed now and may be considered as a speculative project for sup:~srt - polysaccharide threads of controlled diamez2r impregnatet alkaloid and combustion modiflie-rs. Al~.er-natively a less ex-.reme version mignt involve the knowleb €D ce ce Co rml BATCo document for Legal Services : Health Canada 21 October 1999 AL MR A. --RAMONATIO~ STUDY 31AS7D ONI W;.T~ PROPOS~ SzDez~ific Recluczic.-. of heavy mez-als' Cyanide and Ames ac--ivity, Carbony'l compounds, ROx and nitrosamines ~Burley onlv) Heavy metals, specifically cadmium, will :)e mainly presen: ~r insoluble esianue af:er wazer extraction. Significant cyanide and Ames activity may be genera~-ad f r o mi nitrogen in insoluble frac-.4on. Carbonyl compounds mmay be reduced by modification of residue. NOx and rizrosanine -nay be reduced by removal oil nitrate from water solu~',es. R 1 K -N7ATION: Water extraction of tobacco to give 2 fractions. Aralys- fcr imetals and n4trogen in eacn. 2. Treat res-laue: n~ with chelating cocipounds to modif -metal contenz b use en-zyraes to solubillise niCrogen and possibly Polymers; C consicer chemical or physical treatmen-.s to of resicue; i real extr-~c': -3y) to remove nitrate e~-,,. 0 J~b CD CD CO CD cc Lil. BATC6 document for Legal Services : Health Canada 21 October 1999 "7 . ar" Co Carbonyl --ornpounds Aromatic and polyaromatic compounds Cyanide Listea iso Nitrosamines Oxides of nitrogen i4etals including Cd, P0915 Free radicals Additional r--,.-.Donents cthylene have cons~--ered Muza-genic Nitroq--n heeterocvclas we "Aries" ac-~ivltY :S~. : Independent Scieptific zommi--tee on Sno'&4nc- an: Health ('JK) 9 CD CD CD OD CD BATCo document for Legal Services : Health Canada 21 October 1999 2%RLE 2 3'-!OKE C0;4?0NE NT S A ND THE G 'L N'S (zS 1 .Is YN 7'-jE S I S D E L Y ~Al 10 D7 Rol-~Si S I, ?'.,Rc.-, 7 . U 60 - 3-30 31 - 6 HCN AMINO ACIDS, PROTEIN 190 - 300 0.006 10 - i5o "OLA6AL- -.5 i AL -01D.S, VOLPJILE 0.3~ '.S S , N I TR ATE S .1jR SAMINES 61 i D 1 ST i ILLAT I ON' ( FORMED DUR 1 NG 0) CZ 25 .11 1 ROSAX11 N ES CU91NG). NICOTINE AND GBACCO ALKALOIDS C ET A L D --- H Y D E' DIST!LLAT~O.N; CELLULOSE, C 3 3 1 2 STARC~, L.,G,Nlil, SUGARS 3:"7NZ0[A-',PYREN:E SOLANESOL, SUGARS, AMINO AC:---,S, 0.:'- 3 3.4 N.,~.OTINE, TERPENE, LIPIDS, I a 2.6 DU.zN0L DIST"!-LATTC-~,I; POLYSACCHARIDES, 900 - 4 PROTEINS, AMINO ACIDS ... ^d TRANSFER FROAM TOBACCO OXG-1 3 - 7 =RL*E RADT ICALS ? ? ? Sicestreami; 'r*,S XairisLream -L'…. (Z) CD CD CD CD Ln BATCo document for Legal Services : Health Canada 21 October 1999 `ABL- -~'OSPECTS ~GR MODIFYING LEVELS Oc SilOK: CON~T'TU.ENTS BY POI.-IING PRACTICES -10ke Direct Coimponen-_ Consequence Zz~nsequence :ar a net4 C ? I ~ M Geneti c( ?) I arbonyl Compounds Genetic(?) Aroma:ic a.-,c :~311y- Genetic Gene:ic aromatic Comincunds 7- ~; n Q Cyanide ~enet~ C -~;ri n^ Oxides of N~i-_rogen Agronorni c Gene:ic Ni rosa:-,,4 nes Agronomic 3-2-e.:ic Curing f Free ~.::-oncrai c ?) ? Zuring(?) Z z hy I en e Me?.al s Agronomic !:nnet I c(?) ; Ames Ac-.Cv'--v Gene-.ic 1-netic I e :~D. e area :~nsequence ind-,.:ates where selective in th ;ndica-.2-z' 7-a cnmoonent indicated. y be expected to lead ~.o change in :ne co '2'. An Conseq----ence indica-,-as a potential cn -or --hes 00 IS*an a5Su ~,; t" , ? I , -,~, * imption rather thar. baS=- 3n exist-rig evidence. C* co GN BATCo document for Legal Services : Health Canada 21 October 1999 TABLE 4 MIA - -- -"/:S TO ŒCIGARE-.~-' FROM THE !SC !-'ST 1 . JOR P~RM".171ED ADD: Maxinum Allowed Amr,,on4,,;,n Carbonate 4 It Sulphate 4 D;Amraoniu7i hydrogen phospha~e 4 Benton4te 5 Butane-I 3,-di ol 3 Calciur..,. cartmat,a 1 , . . . Calciur,--. z;nioride 5 cellulose 5 Citric Acio 4 Dextrin 4 Diatomaceous earth 5 Glucose 10 Glycerol 10 ,nvert sucar io iquorice 4 i'iagnesiu , -,, chloride IMethy1cellulose 5 Pozassium carbonate 5 Propylene glycol 6 Sodium cainoxymiethyl, cellulose 5 Sodium viloride 5 Sodiuna hYcrogensul.pnaze 5 Sorbizol 8 Sucrose 10 Use of the above is also restricted to total amount of these and other 'List 1' rnaterials not exceeding 15'. by weignit in the tobacco blend. .t¯,.Ab CD