Tobacco Documents Online

Ricf9rd 050 day. Hcwever, ploving throughout a smoking s for cigacette ~posures 4TO~~ active markers and bloods as~Y be carried smoke experi~u with M~ that effective expos~e can comp~nts have shown C°ndiiionsL well controllcd e~imals has recently out und~ f~dy ~~e for exp°SUre of larg since A pew ss~n gng enetation is closelY controiled. (12). Smoke g b direct been d~~ ci asette by. a piston rather ~en' and smoke is drawa from the g way a fixed P~ volume is 1~ to ~,alation by ~~~' in this ln this machine is very s'm' ~w that ~ke produced ' u,alyticsi smoking u'~~ ~ under standard conditions by ~ ~t p - i machsna. : CpMME9M~ • • sure of both sma11 and large ; ~~ ~tn ~ for eXP° study noted has , M~ methods effect, almost every and a wide i ~~ to ~cco smoke. in ~re tcchnique. of °Xp° ' ~ of a different type ; ~VO~d the stems have been ex~~' been paid by ~ n~ of ~M~ ry g therefore that little attention h~a of exposun ~ It is not sutp~ of smoke generation ~ tems is ~ to the technologY with design of ~P°Suce sYs F ~~.~ ~ of con~~ of aPPm~ation of the due in most ~ to lack °f the srtwk~g studia ~ ~e~ te } undess~~b ' tht results of manY are equivocal ~~},~d. However, ~nogcnesis, ~ pcobiems c~Iy those relating to ~ ~adequate ~ repoRed, Puv' now ~nsidered to be bas'scally ~~ of what ~ ~n to techniq~s- consideration has been gi ,rariety of the ~ expusure which serious the difficulties y those studies in stems, l °f ~ ~ d~ ~a ~aracterisation d ~ ion ot the practica ~ met~ deYeloP~ gives some in studies with ' .,p~ in carrying °Ut wen{ontsolled inhalation toxicity have b een snado on exposure 1 m ke }tecently, suBS°Stions for toxico}Ogical _ tobacco scnO ' =uncntal conditions stem d~gn and on ideal exPe 4 5~0. Such guidelines mzY be i sy 14 39 9 lann~g of stud-us with tobacco smokc ( smokiog studies. Critical P tIowe~r• i ~t, in the design of eoucse, essenti~n i ~lpf~~ in p al work is. i anY expetimental biologic ; 10'1 , . ~Y'~ ;za,•+ PC ,r~ '` ~ :«r _ , r PIw"i".._.,+.,.~:,:, '~. '~_Y- t-'se"••{+ - ~ ~ .~ l~. V'R2=_i'-'-r". • . t-.r AC+~~..titi.};,~ j- ~.4 asa• ZrY: .~?, ~- sdY'r~~F.

YoUI, No.2,1 p7S Aninal Itdmlafion Studies wirlt Tobacco Smokr • R icliard Binru e 1 0 theoretical criteria for idealised studies on tobacco smoke inhalation may be unattainable in practice. Studies with experimental animals exposed to smoke will always be a compromise between ideal and practicable conditions. It is now generally considered that the generation of smoke from cigarettes in smoking machines should simulate as closely as possible 'average' human smoking conditions, based on standardised burning conditions of puff yolume and puff frequency with burning down to a constant butt length. The means of attaining these standard burning conditions_have been the subject of considerable discussion by some workers in the field. For example, is smoke generation to be by conventional drawing of air through the burning cigarette or is "reverse smoking',in which air is blown through the cigarette, an acceptable alternative? In a*similar vein, should the position of cigarettes in smoking machines be horizontal, at a slight angla to the horizontal or vertical? Should the puff profile be square or bell-shaped? Such detailed questions, based on the enthusiasm of the chemist for exact dupliation of analytical smoking conditions are perhaps over-emphasised in view of the present state of development of inhalation toxicity techniques for work with cigarette smoke. Current- ly, no highly scnsitive, widely accepted methods are available for assessment of biological activity of smoke in relation to carcinogenesis, emphysema or branchitis. Pre-occupation with often trivial details of chemical composition of tobacco smokes obscures the more urgent need to develop convincing animal models, based initially on the demonstration of distinct changes in biological systems exposed to tobacco smoke. Exact duplication of human smoking characteristics, smoke delivery to the lung and biological response can never be achieved in animal studies. At present, the most pressing requirement is to demonstrate marked, consistent and relevant biological effects in experimental animals, under exposure conditions which satisfy some of the criteria that have been suggested. The basic problem facing the inhalation toxicologist is one of being able to apply an adequate controlled dose of the test material to animal 108 systems As with other aspects screening techniques, both sh( practicable memzs available. Practical difficulties of the t~ on the experimenter. In add occurrence of spontaneous res particularly rodents, which can conditions, may pose addition: ' interpretation of inhalation stud lung pathology. Such practicil smoke an: now being n:cognis workers in the field (46,47,48',9t The reiIisation of the diffic smoking studies has come as t}ie much of.rhich has produced nc surprising that only qualified inhalation toxicity studies wi carcinogenesis studies with sn experimental studies relating to been impi'icated. Smoke itself is markedly to "dose" leveT.s or concentration: which can be used. Workers attention to optimization of exF with minimum overt toxic respe . The latter problcm of assessin . exposed animals, is now under 2 Routine measurements of blood fairly commonplace in smoking O an indieation only of the degre. cigarette smoke. Blood nicntine w been used as an index of the 3egi}a Apart from the anal)rtical compcA nicotine is absorbed into the t~ ~ -4

~ :ion• nals ~ and :rom sible :ning ~ t to a .rning some ke by werse t >table :es in tal or 3 r i st for nt uf crent- e for !nesis, tils of irgent a the ed to istics, er be srnt is cts in tne of Rtritwt on Enrbonme,rral fftafrh Ridffd B;ma aspects of toxicology, the aim must be to devise systems. As with other based on the best ~~ and long-term, both ~ 0 ~ u q screenu~ te~ ~ pyccticable mauts available. pnctical diffculties of the type mentioned impose ~n limitations ex rimenter. In addition, it is well recognised that the on the Pe disease in laboratory ani~s, occncrata of spontaneotu respiratory rodents, which can develop in stock maintained under good particularly additionai problems to the experimenter in the conditions, may Po" articuiarly those involving deta~'ted iaterpretation of inhalation studies, p with cigarette ~ limitations of wor a b ~ p*a~l S u lung pathology. ex ezienced smoke are now being recognised and acknowledg Y p arorkea in the field (46,47,48 ,96)- roblems associated with The reaI'isation of the difficult pnctical p • smoking studies has come utfie result of considerable e fesnlts`lt islnot much of which has produced negative or uncem+in~'g tance can be given to many surprising that only qualified accep inhalation toxicity studies with smoke, not only in relation to ~n~ studies with small and large animals but in other ar ~n~ experemental studies relating to diseases in which tobacco smoke has a t ' 4Z f f a ~- ~ a > :~ T ' 1 .;... ~ ' ~ , 'E, i ~ , ~.,~J ~ ~ -W» ~ ~ ~e~7~- ~ ~~r„, : 'r ~CrM ~~-~ ~~ a fi~ .A7,7. ~ •.-:~'~.~Y , ,t.. ~; ;;-. ~ r. . ~ 4~: been impliated toxic and to date this toxicity at high dl k 7~~"'~,j}~ y e is mar Smoke itself "dose Imls or concentrations has limited the degree of exposure siderably more . ~~ : which canbeused . Workers are now paying con attention to opti~tion of exposure conditions, for m~mum effect of dosi~ry., h n s>~sea- -•.~- M 16 -~ M i e ~a- _ t toxic response, and to t : ~ ~ um over witlt m~i>~fm n~~~ainount,,,afJ.~ke applied o~~ ln:0 g: . . ~ ~_ ~~ Yat3ous ro po tiadeiactive-cons~deration'by 8.~ , _ ~ . ~" - 3urin and ifter smk'ng art~ COl ~ d ~- ~ Y ~: . mentsrof:biood" e~ .r..t i~. ., . gh ~ ~~ ~,~sure ~~ . ~7) ?Ithou n 492 d y" __ a ' ~ , ies (1 n stu smoki g ~c~~ commonplace ~ i ~~ e seovs :pltase. of e of exposure to~ ~ ~catSbtf'on~'lY, less fre umtly~ q ;~ ~~ x ~-.~; s.. ~„~-~az... ' =' -gsstte-anoke^Blood :?n`cotine deiersnui~~,...-r- 92,9 7 ~ culat ^--- ...• .~...'~~ ~ h d u an sn ex of tliE3e85ee of exos~re t_o_pa~a '~ ~ ^Y beea use , ' hcation~and.the nP, Y~ - o .~.. Om_tI1G.;2IIa~~~ ~ ~_ . ~ ~r~ itt:fJ i11COtiDG~ d' ll ~ze ; ~. r ~ ~O Se { rb- ~ 0 s tha~l.oo_faad ~mcotine- abs L ~ - ~ ~ 109 ~.., .:~,P,/r~t,,,~F M •:n ,r.~ ~ ;".~f"~t'ay~ ~ _ ' '~` -"-n ~,s..L C,,. t~~ ~ S -~~. ..}.yr~~~. yp~~ •. .af.~. •~ f~•*~ . ~~'_~~..w1, ~a' .•+C~Sbflil~,yw- •~~~(_ T. +j•+ ,r r -~.JJ'f• +.4J ~ I - ~ 4 2 • T - _ 0 ~ ~~ .~~~ P r ~~ i''r~ Q i ' l ~~ .

1 Yot1f, No.Z,197S Anrma17n1afation Studies with Tobacco SH3oke - . ~ .~~,.~_ ) ~e~'~the~*ipottr.Phase;and_u there o[~ ol . eIi~blo routine" 'I 3 -Work wtth added radioactive materials carried in the particulate phase of smoke affords a relatively simple means of assessing smoke dose; and some work in this area has been reported, as well as similar studies with unlabelled materials (98). Autoradiographie- studies with polonium-21 0 have shown labelled material deposited in the lungs of mice following exposure to smoke, although considerable amounts were also present in the nasal passages and gutro-intestinal tract (99). Dontenwtll (27) has shown that relatively latae amounts of C34-labelleed smoke deposit in the head as well as in the laryngeal region of hamsters exposed to dilute smoke. Page et aL, (100) investigated the deposition of labelled particulates in mice, and found more than 70% of respiratory tract activity in the head , region, particularly the nasal turbinates, with the remainder distributed in the various lung regions in differing amounts. Only small amounts of smoke may actually reach the pulmonary system. Bretthauer et aI. (16), for example, showed that approximately- 2.5% of available polonium- 210 was inhaled during an 8 minute period involving intermittent exposure to labelled smoke. Davis et aL (101) found approximately h d f ut t e 10`~'0 of available mainstream total particulate material depoatte respiratory system of the rat after intermittent exposure to smoke diluted with- air. Dosimetry studies, aimed at optimising exposure conditions, are a relatively new development in methodology for inhalation toxicity studies with smoke, and also other materials such as pharmaceuticals. Such studies will be important in the establishment of more satisfactory techniques for inhalation experiments with tobacco smoke. This review of pubiished data is not completely comprehensive, and an even greater amount of unpublished information has been aceumulated. Bearing this in mind, it is clear that a great deal of work has been carried out, involving invcstiga.-ion of the effects of smoke on a wide range of biological systems. Currently, there are no widely 110 Ricluad lJFnnr 4 aeeepted, definitive anirnalstudie in relation to smoking, nor any asscssment of relative risk associat of smoke. However, recent publi, ments in experimental technique materials by inhalation studies m past. . The present state of develop relation to studies with smoke is si "Most of the inhalation stu suffered from the lack. of 6a Failure was predictable,in is>tta: rodents to concentrations of moderate to heavy smokers, a, the order of 3 per 1000, a ca usual laboratory tests. If this N to extremely high concentratio produces no cancer, however, lower concentrations of polYn does produce lung cancer (10 the low dose problem are nc ex adequate mastery of *our, inhalation study of cigarette s meaningful". This a.varcness of limitations ~ date should stimulate an interes• systems based on sensible specif biological problems, with atteml allow comparative studies. .

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