M-f-, 17 __. of tho pT at i on f I MoctinS,. nxi April 20 1972 of t, stil,.ivct to Avoid the cillost.1tic. of Effects of tol.)Iccb smok,2. The background of. the work concerning the tGxicity of tcbacco smoke has bf-en partly to define toxic -~ubstati4e:~, in the smoke and partly to study some biological functicris influenccd by c):poroire to tobacco smo*,;.e-. These biological functions ',,Zvc bc?n: 1. Ciliary, naoLverant ir. tho trachea h6tit in vivo Cnd ia vitro. It 1Y.-I.-t been shovit that the muount of tobacco cach puf-: and the different chemical1v dcfin2d substanccs in t,,.c sm~.>',~c havc a clear dose response relationship to the effect on the ciliary iuovQ!-.. IT. TI)e studicr,--of the reaction of free litnj~ cells to tobacco SM01,C exposure show that after a sl;ort term exposure the number will dPcr1N":;-_,!. -1 f, bovi-o-ri 0 Will be continued the nunb I iv..~,Ase. cr wil 111. The pulnio.a. --clear.Ince h. C a ry a s also been stuJied, partly as_ a b a't,:! r i n-' clearancc,, partly a5 I parLicul.at.e c1corance. Both functiors %.%_-re ~'Ocrillstd after exposure -to toba6co =Oke. A re --a0r:'1,.,b1e after 'to rvh~lcco Au wi--11 III; k4 Bike epi ibel i wa -and' wrif)~-r of mit tos is. 302058919 BATCO document for Province of British Columbia 19 April 1999 Fff,rr of rct!--o wit,, addif i,,,- Thesc abovc wc:) ~Eioticd 1-,,ur biological NncLioils have bven ur-d ~L , LCSL Lho effect Of so.-.)c addiLivus to tljt! tobacCb, partly oxf-la:-litic cirrarr , nrid pai -1), phenN 1-iirJiyl-oxatliazol MM) . Those subs ances haVe I-P" f-f-4t!tCd rr~~ C-Ily tit additive to tobacco but also given intraperitor-:cally and jn~--rornlly. 1. Dotli oxolimine citratc and MO shuw in anticiliostatip rffcct when admini stered in 311 tIv-- above vicut ioned ways so that the an inals . . were ablc 4a smoke a statistically si-gnificni,t more numbers vf ci.-arettas after tzearment with vxolamine citrate or PNO titan without. M-11- Doth conetrninj, macrophages and leukocytes il- was possible to- show a lejF reactior vith smo!~.e frond tobacco containing about 1.52 FMO than fror4,to"al S:ankc after a fou*r weeks exposure to four c.-Carettes a day. Ad 111. Concerning the effect-on pulmonary clearancd if was Shown tjat l both radioactive And viable coli bacrei ia. disappeared a littl.e,,quicker after exprisure to' tobacco srpohc vitIl 1"No than without MO. Ad IV. AfLer six weeks exposure to tobacco smoke with No a 5 addttive j the following results could be Shw'n- a-) The incrqAu;-aL tl:~-, nu~alwr -C :-,-b1-ct-nz~'.Ti wAi, tt,'u I t i e E sthan aitur 00 exposure to tobacco SMGke-:WW,0Ut PHO, h) so was-the thickness of the epithc) it1::1. C) 1he numbcr t?f,1:1itt',ai!i Lhtl Sr"p was,~cxposed Lo tobacco with YN,0 as r-OM 1) ar a Wth- -ve 302058920 BATCo document for Province of British Columbia 19 April 1999 3. In further evaluating the protectivc- cf1ects of MMO guinei pifis have been exposed t;' heavy co;acvntratL~t, of acrolein for about 5 ninutes. Thereafter Lhe AAimml-bm,,e bne-n -:rcnt-re frcqu-,citly, perorally-tip to 80 hou-,;& after L~,c end of Lhc exposuru. After that zi---- the ani~iials were sacrified and t"-chca, ~rvnchi anl lUll,,S W,:~rL hi.S~C- Pathologically examined. There w3s in mort c-asL'S a statistically &:L-nificai: A dif,forence in the degree of infl.-i-mration in Cie tissue indicating a stron,3 protecti-ve errL-et Of F-30. 302058921 BATCo document for Province of British Columbia 19 April 1999