Tobacco Documents Online

Adult mortalitv from passive smoking 259 Table A]. Annual U.S. male lung cancer deaths from passive smoking Rtlative Rtsk , Constant at '_.1 Age of Death Neversmoker Death'i Rate per 100.000 ~ Nonsmoker Population 1000's Fraction Exposed Exposed Populatton 1000's Excess Death Rate Deaths 35-39 1.8 ~ 5156 0.71 3815 1.09 42 40~-44, 2.9 ' 4136 0.72 2980 1.78 53' 45-49 4.5 3477 0.70 2440 2.80 68 iI 50-54, 7.01 3431i 0.66 2260 4.46 101 55-59 11 3423 0.63' 2155 7.15 154 60-63 16, 3489 0.59 2054 10.7 219 65-69 23 3150 0.54 1695 15.9 269 70r74 33 2443 0.45 1099 24.3 _'67' 75-79' 49 1712 0.3' 633, 38.3 24_°' 80i84 72 921, . 0.27 249' 61.1 15'' 85 - 95 516 0.08 41 96.0 39 Totals 15.9 31844 0.61 19420 8.26 1606 Appendix A Derails of death calculations Tables Al and A2 show the details of the death calculations for male lung cancer and female cancer other, than lung and are similar in all respects to Table 6 in the text except thart no d'eelining relative risk calculation is shown for male lung cancer since the evidence that was available (Hiravama. 1984a) indicated no suchAecline. In Table A3 the details are given for the development ofi the never smoker relative nsks for heart disease that were use&in the death ~ calculations. As noted in the text. the 1963' neversmoker heaR' death rates by 5-year intervals were ob- tained~bv dividing the never smoker coronary heart deaths in HammondTs (1966) appendix. Table 14, by the person years in his appendix tables 2a and2b. Reduction factors to account for the change in heart death rates between 1963 (end ofHammond7s study) and 1984 were then developed by 10:year age intervals from the age specific heart death rates in table 24 ofiHealth U.S. 1986(NCHS.1986): These reduction factors were modified for the fractions thought to be due to smoking which were taken from~a staff report of the Office of Tech- nology Assessment (OTA. 1985) to yield a combine&never smoker reduction factor. interpolated back to 5-vear age in- tervals. for application to the Hammond never smoker death rates. These modified rates. which are forenrollment age and therefore about 2 vearsyounger than age of death. were then, plotted~ agairut age of death on semi.loe graphipaper. Treli lines were then drawn through the female and the male points to yield the values in the last column of Table A3. Tables A4 and A5 are simply the details of the heart death calculations as in Tables 6. Ali. and'A2'for cancer. The deaths shown in Table 7 resulting from the corrections for misclassification were calculated from the relative risks in lines 4 of Table 5 taken as constant over the age ranee. The modification of the observed relative risks for smoker mis- classification as shown in Table 5 are based on misclassified smoker relative risks calculated as follows. Based on as vet unpublished work of Wells on misclassification it was assumed that self-reported current smoker relative risks for male and female lung cancer in the U.S. and U.K. were 11 and 7. and 4'.6 and 2.7 for male and female current smokers in Japan Table A2. Annual U.S. female deaths from cancer other than lung from passive smoking. Exposed Relative Risk Constant ati 1.16 Relative Risk f Neversmoker D R Population T bl 6 E Declining Age o Death eath ate per 100.000 a e ) ( 1000's. xcess Death Rate Deaths RR Deaths 35-39 28 5781 3.9 22.5 4.5 13211 \V 40-44 48 . 425'- 6.7 285 29 14'11 © 45-49 80 3423 11!.2 383 2 0 1--t9 ~ 50-54 125 3355 17.6 589 1.56' 1579 55-59 190 3495 26.8 937 1.30 1591 60-64 265 32-18 37.7 1219 1.18 1352 V1 65-69 355' 2912 5711 1487 1.12 11" ~ 70-74: 470 2030 68.7 1395 1.08 729 75-79 600 1472 89 0 1310 1.05 4'?1 ~ 80-a4 750 547 114.7 627 1.034 138 ~ 8-S* 900 100 14117 142 1.0:21 20 ~ Totals 256 30595 28.1 8599 11165 '

260 A 1 %Le11s Table A3. Development of 1984 neversmoker, heart death rates versus age. Death rates from Hammond (1966) Age at enrolltd age Range per100.000, Females:. 1984 1984 wNeversmoker Decline. Fraction Neversmoker Hammond's heart in heart of,deciine Death Rate N.S. D.R. death rate DR's 11 due to as x of1963 corrected by age of 1963-83 smoking (smoothed) for decline death 35-39 71 49 3.5 _' 0! 48 0 . 40-44 14.1 55 7.7 4.4 45-39' 20:.3 ' 60! 12.2 10.2 37 0 50-54 35:5 63 28.7 23 55-59 104 64 66 51 01 60-64 243 64 156 113 65-69 475 64 304 240 37 0 70-731 %f 64 615 480 75-79 1648 65 1072 870 35 0 80183 2774 70 1942 ' 1550 85+ - 21 0 79 - 2770 .Ncles 35-39 T 76 0 20 48 50. 40-44 79:5 77 61 36 45-49 85.5 78 67 68 42 50 50-54 220 77 169 128 55-59 397 75 298 237 37:5 ?5 60 -6s' 741 75 556 412 65-69 1089 76 827 730 32' 25 70-74 1936 76 1472 1150 75-79 2639 77 2021 1850' 25' 10 80-84 a'373'. 81 3343 2950 85+ - 1.4 10. 86 - 3700 (Hi'rayama. 1984a): The 5% of ever smokers who were as- sumed miscliissified as never smokers were assumedito consist of 239e light current smokers and 77% long term exsmokers. The excess risks for currenr, self.reported smokers were re- duced by 2/3 to yield~ relative risks for misclassified current smokers an& by 11/12' for relative risks of misclassified exsmokers essentially as was done by Wald er al: (1986). This resulted in misclassified ever smoker relative risks of 2.4. and' 1.85 for males and4emales in the U.S. and U.K. and 1.5 and 1.25 for Japan. Worldwide misclassified smoker relative risks were then calculated to be 1.8 for males and 1.6 for femalesbased on the proportion of "western" and "eastern" cases. The false relative risks shown on lines 2 in Table 5 were then calculated using the formulae in Welis' unpublished work. For female cancer other than lung. the smoker relative risk of 1.05 was taken from Hammond (11966) and used as is since the effect is too small to make any difference. For ischemic hearr disease the ever smoker relative risks from Hammond' Table A4. Annual'U. S. female heart deaths from passive smoking. Relative Risk Relative Neversmoker Exposed Constant at 1'.23 Risk Death Rate Population Declining Age of per 100:000 (Table 6) Excess Death (Table A3) 1000's D.R. Deaths RR Deaths 35-39 2.0 5781 0.38 22 4.0 91 i0ii.t 4.4 4252 0.84 36 2.0 97' ~ 45-49' 50-51 10.0 23 3423 3355 1.91 4.4 65 148 1.32 1.17 85 114 ~ 55-59' 51 3495 9.8 3" 1.17 :65' ~ 60-64 1,13 3238' _2.1 713 1.17 548 . .~ 65-69 70-7.1 240 480 2912 2030 17.7, 97? 1385 1973 1.17 1.17 1062 1505 IiA 75-79 870 1472 180 2647 1.17 2010 80- 8a 1550 517. 33+t 1828 11.17 1374 ' ~ 85+ 2700 100 607 607 1.17 J51 ~ Totals 291 30595 31.9' 9768' 7602

Adult mortality from passive smoking Table A5: Annual l' S. male heart deaths from passive smoking Neversmoker D R Exposed P Relative Risk Constant at 1.31 Relative Risk f A eath ate 000 100 opulation (Tabl A1) E Declining ge o Death per . (Table A3) e , T000's xcess D.R. Deaths RR Deaths 35-39 20 3815 4.9 187 5.2 780 40-44 36 2980 8.9 265 3.0 879 45-49 68 2440 16.9 41!1 1'.9'- 929 50-54 128 2660 32.11 723' 1.42 951 55-59 237 2155 59.8 1289 1.28 1_'01'. 60-64 412 2051 105 2157 1.28 2009 65-69 730 1695 189 3195 1.28 297. 70-74: 1]50 1099 304 3341 1.28 3103 75-79 1850 633 500 3162 1.28 2933 80-84 2950 249 819 2039' 1.28 1887 85. 4700, 31 1377 565 520 Totals 521 19420 89'3 17335 181t.s (1966) were taken as 2.3 for, males and 2.0 for females.. The excess risks were reduced by 2/3 to vield relative risks for misclassified ever smokers of approximately 1.4 for males and 1.3 for females. These were used worldwide with V4'ells' un- published formulae to calculate the false heart disease relative risks shown on lines : of Table 5. Appendix B Relatrt.e risks for all'causes of death, and for emphrsema and chronic obstructive lung disease Data relating all causes of death with passive smoking for: females have been reported for four prospective studies to• talltng 9537 cases as shown in Table B 1. The combined relative risk is 1.165 with 95% confidence limits of 1.11 to 1.22. The onlv male data available are 75 cases from Gillis et aL (1984)) with a relative risk offl 1.0 so no male analysis was made. The calculation of the total number of female deaths from all causes for passive smoking is shown in Table B2. The total., 3a.1641. is considerably larger than the total for cancer plus hean of 19.359 shown in Table 7. Some of the difference is due to uncenainties in the ealculations, but other causes of 261 death that might contribute to the all cause total. based on data in a pnvate communication from Dr. Htravama. are cerebrovascular disease, other hean disease. diabetes. and ulixr. Hirayama (private communication. also reported preli- minarilv at 5th World Conference on SmokinQ and Health. Winnipeg. 1983)provides data relating deaths from emph.- sema with passive smoking in womem Hisrelativr risk. based on 106 cases is 1.3 with 95rir confidence limits of 0:85 to'_.05. Kalandidi'et a!_ (1987) report incidence data for chronic ob• structive lung disease based on 103 cases with an adjusted relative risk of about 1.4. Lee er aC (',19861 report incidence data for chronic bronchitis from spouse exposure Based~on 17 cases the adjusted relative risk is 1.22. A,wetehted a%eraee of these three relative risks would be about 1.3i. The only neversmoker death rate we have is from Hammond (1966) for emphysema at 2 x 10-`. Assuming 76 r exposure. the excess death rate for passive smoking using Eq. (2) would be 0:55 x 10'5 and the total deaths for an.exposed population of 30.61million would~ be about' 170. Even, if this number iss doubled to take into account deaths from formsof chronic far obstructive lung disease other than emphysema. it u stillT below the total for cancer and ischemic heart dtsease. Table BL. Female relative risks for all causes of death from passive smoking. l All Exposures Mantel Trend Locale Tota Cases RR 95% C.L. 1•tail p Cohort Studies: Hiravama (1987) Japan 9106 1.17• 1.12=1.23' 0:(ItKK)1i Gillis a at.' (198t), Scotland 102 1.45 0.91-2.30 Garland et a!. (1985) California 79 1.06 0.65-1.73' Vandenbroucke et at. (1983)" Holland 250 0.79 0.57-1.09' Combined Chon: 9537 1.165 'Dr. Hiravama (private communication):provided the data necessary to calculate these items., 'Data from 25 vear follow up: Relative risk w•asA!89 (0.50-1.62)ifor 1,5 vear follow up. This stud% is weak in,that exsmokmg women,were tncluded among the "nonsmokers." and nonsmoking women,exposed to exsmoker husbands were included in the "nonexposed " The weakness of the study, is emphasized in that the smoking women had a lower overall death rate (33.a'~/rYthan thc nonexposed nonsmokers (38, l1: )_

262 ge Range Nevetsmoker Death Rates (rom Hammond (19661 at enrolled age per T00.000 35-39 136 .t0-4t 178 45-49 254 50-54 352 55-59 561 60-64 867, 65-69 1492 70+-74 2585 75-79 4790 80-8s 8J08 85+ - A. J Wells Table B_. Annual US. female deaths from all causes from passive smoking. Decrement due to heart death rate 1963-84 per 100.000 Corrected Neversrnoker death rate at enrolled age per 100.000 3.6 132.4 6.4 17;1'.6 8.2 245,8 16.8 335:.' 38 523 87 780 171 13211 346 2239 576 4214 832 7576 -- - Totals Deaths per million total population Lee er al: (1986) report data on chronic bronchitis life long nonsmoking in males exposed,to a smoking spouse. Based on nine cases the ad)usted relative risk was 0.34. However. for general' exposure (a' cases) a positive relative risk was ob- served. No analysis of these data was attempted. heversmoker: death rate t d P l9 io F Relative Risk Constant at.1.165 correc e to age of death per 100.000 opu t n exposed 1000's raction of population exposed Excess D R. Deaths 120 5781 0,94 17.1 991 155 J'-s, 0.92 21.2 9a-t 212 3323 0;89' 30.5' Ioi-t 300 3355 0.87 43.3 la5'_ 445 3495 0.81 6-t15 _254 675 3228 077 98':8 31901 1070 2912 0.70 1583, .1609 1830 2030 0.59 275.2 5596 3250 1472' 0:49' 496.1 7303 6000 547 0:29' 9-t-t.8 5168 10!000' 100 0.10 1623 1623 30595 1]1 7 31]6-t 143 Appendix C Rate difference mode!'for assessing female ischemic hearr deaths from passive smoking A rate difference or absolute risk model was investigated for female ischemic heart disease in order to compare it to the relative risk models in ability to translate experience from one type of culture to another. Female ischemic heart disease was chosen because considerable data exist and because heart disease is the largest contributor to total deaths. Also. the relative risk model seems already to be welCestablished for lung cancer (Wald ct al:. 1986; Blot and Fraumeni. 1986) so a comparison~in another disease category appeared to be ap- propriate. Data from the four: cohort studies (see Table 4) were com- bined using the direct pooling equations described on page 183 in Rothman (1986). The two case/control studies were omitted. Although their combined rate difference was essen- tially the same as that for the cohort studies, no good way could be found ao combine it with that from the cohort studies. Death rates for exposed and not exposed populations were obtained by dividing the observed deaths in each category by person years which were equated to the mid-point populations multiplied'bythe years offoll'owup. The rate difference was then obtained by subtracting the nonexposed death rate from the exposed death rate. Vanances and weights were calculated by Rothman's formulae., The combined rate difference was obtained by summing the weighted rate differences and di- viding by the sum of the weights. Confidence limits (95%): were equated',to the rate difference =1.96 (variance)°=. The results of these calculations are summarizcd'in Table Cl. The cohort data were also combined using Program 7 of Rothman and Boice (1982) ,', with results essentiallv,idemical to those shown in Table C1 for direct pooling. The relative heterogeneity of the relative nsks ('RR) vs.,the rate differences (RD) can be approximated; by considering the range of RR- 1 versus the range of RD: The range of RR-1 is from 0;16 to 2.6 for a factor of. 163. The range of~ the rate differences is 3.7 to 262 'or a factor of 71. The ratio for the two large studies, Helsingeral: (1988) land Hiravama (1984b), for RR-I': is 0:2d" 0.16 = 1.5 and for RD is 20.7/3.7 = 5.6. The 95"c confidence limits for the rate ratio combination is tighter than for the rate difference combination_ ,#lso, the Hiravama study dom- inates the rate difference aggregation muchlmore than inithe rate ratio aggregation. providing 64% of the combined weight (last column of Table Cl) in the rate difference case vs. only 17 0 of the combined weight in the rate ratio case. Table C1. Rate difference c alculations for fe male i schemic heart disease. T Relative Risk from Table 3. Rate difference x 10'' Wn¢hts fo RD ~ RD x ~ h otal Cases RR 95% C.L. RD 95Pr C.L. r x 10-" weig t x 10- yN~' Cohort Studies: Hirayama (d98sb) 394 1.16 0.9- 1.4 3.7 -2.1- 9.6 11110 41 a Gillis er al. (19fi3) : 21 3.6 0.9-13'.8 169.1 30.7-307.6 2 31 Garlan&er al. (1985) 19 3.5 0;9-13,6 262.2 36.0-188.4 0 & 2.0 Hetsin¢ n a!: (19681 988 1.25' 1.1- 1.4 :0:7 -0.2- 41.6 88 IR.2 Combined Cohort 1522' 1.23 1.1- l.l 5 1 -0:2- 11.1 1201 65 0 ~

Adult mortality from passive smoking Table D1. Regionaliparticle deposition from mouth breathing of side stream smoke Fraction of inhaled Aero- Relative particle mass deposued` dvrta i V l M m c diameter Cube of Relative o ume (Weight) ass Distribution mouth trachro• µm diameter eonantration' per 0.liam , 'ii throat, bronchial alveolar 263 F1ass deposited as r~ of totall mass inhaled' 0.20 .008'. 1.5 0.006 0.3 0 0 0.13 0.0a 0.25 .016 6.5 0.051 2.4' 0 0 0.1?' 0:29 0.30 .0.7 10I0, 0.135 6A 0 0 0.115 0:74 0.35 .043 13:0 0:280 13.2 0 0 0.108 1 43 0 40 .064 13.01 0;i 16 19.6 0' 0 0.10 1.96 0.45 .091 6.5 0;296 14.0 0! 0 0.105 1.41 0.50 .125 3.5 032S 15.5 01 0 0.11 1.71 0.60 .216 1.25 0.270 12.7 0 0 0.115 1 .4b. 0.70 .343 0.5' 0.17~_ 8.1'. 0 0 0.12 0.97 0.80 .51L 0.25 0.128 6.0 0 0 0.13 0_78 0:90 .729 0.05 0.036 1.7 0 0 0.14 0.24 1.00 1.0 0 0 0 0 0 0.15 0(K) :.1!18 99.9 11.08 •From Hiller rr a!. (19821. Fig. 1., 'From ~Hevder (1984).,Table 1. 250 cm'fsecond mean flo%% ' rate. 4 second breathing cvcle. This domination of the rate difference model by the Jap• anese study is evident from some rouch death calculations. Use of the combined rate difference (5;a x 10") with the exposed female population from Table A4: (30.6 million)) yields total deaths of L6fi2 compared with 9.768 calculate& from the constant rate ratio modell VJhen the rate differences are plotted against age of death~and weighted accordinglv it is found that the "westertr " rate differences increase sharply with age whereas the Japanese rate difference stays constant at about 4 x 10'. Constructing a weighted average of these ••western-' and ' eastern" death rates for each of the 5 vear age ranges and multiplying h}• the corresponding exposed pop- ulations yields a total of about 2.100 deaths compared with 7.602 in the second relative risk modell Use of the Japanese data alone vield's about 1.200 deaths. Use of oniv the "west- ern" data (Gillis er al.. 1994: ',Garland ei . al.. 1988: Helsing ett al: ) at a constant, rate difference yields 7,950~deaths while use of "western~' data with the rate difference van•ine with age yield5 about 30.000 deaths. Thus. the death caltulations using rate differences are quite vofatile, Also. it is evidentt that with the rate differences it is not feasible to carrn- over the "eastern° experience. in ischemic hearr disease at least, for use in a"western" setting.. Accordmglt. it' was concluded that the absolute risk model' is not as suited to combining risks for passive smoking asthe relative risk models. Table D3: Regional ~ particle deposition from nose breathing of sidestream smoke. Aero- i Fraction of inhaled particle mass deposited" Mass deposited as K of total mass dynam c Mass diameter distribution mouth ttachco- inhaled µm % . nose throat bronchiai alveolar nose alveolar 0:20 0:3 0 0 0 0.19 0.00 0.06 0125 2.4 0.005 0 0 0.172 0.01 0.41 030 6.4 0.01 0 0 0.155 0.06 0.99 0.35 13.2 0.015 0 0 0.13R 0.20 1.82 040 19.6 0.02 0 0 0.12 0.39 2.35 0.45 14.0 0.03' 0 0 0.11-2 0.42 1.70 ~ 0.50 15.5 0.04 0 0 0.125 0.62 1.94 0.60 12.7 0.05 0 0 0.1_R 0;6,t 163 0.70 8.11 0.06 0 0 0.13 0.49 1 05 0 80 6 0 077 0 0 0 0:13; 0!46 (1!Rn', L . 0.90 . 1.7 . 0.093 0 0 0:137 0!16 0;23 #" 1.00 0.0 0.11 0 0 0:1a 0.(10 0,(uiI ~ 3.45 1'_.99 °From Table D1!. ~ "From Hevden(1984). Table 2. 250 cm',second'mean.OoM rate. .4 secondbreathtng cycle..

264 A J MctIA Table D3. Smoke Particle deposition patterns in direct and passive smoking Direct Smokintt Passive Smoking Direm, Passisc Entry site Particulate inhaled per day. me. Mouth :a0 tiose 2.8 86 Particle Size inhaled. µm 0 7 0.4 Particle size exhaled.,µm 07 04 Retained in nose, 5r 0 3.5 Retained in mouth. i7', 25 0 Retained in tracheerbronchial reaion. % 35 0 Retained in near alveolar reeion_ % 19 0 Retained in deep alveolarregion. 4c 9 13 Totallretained. °k 90 16.5 Particulate retained. total. mg. 192, 046 177 Particulate retained. alveolar. mg. 48 0.36 133 Particulate retained. deep alveolar. mg. 2-1 0.36 61 Appendix D Dose considerarions As noted in the text. there is a wide difference between the observed'disease ratio between passive and active smokers and the ratio of cigarette smoke particulate retained by, each. Also, the cancer sites appear to differ. On the assumption that part of these differences may be due to differences in deposition sites between passive smoking and active smoking, calculations were carried out to try to pinpoint these differ- ences. The calt:ulations for passive smoking are reasonably straightforward. Stober (1984) has summarized all the uncer- tainties in this type of calculation. Nevertheless, the best ap- proa& appears to be to use the data of Hiller et al. (1982) for the particle size range of side stream smoke, centering around 0:4 µm, and the mathematical lung modellof Heyder (1983), for inert particles. Integration of these two data sets yields a distribution of deposited weights by particle size for mouth breathing (see Table D1) which. when summed: vields exactlv the total': deposition observed by Hiller et al:. (1982) indicating that the Heyder modeliholds for passive smoking. The same inhaled particle size distribution camthenbe applied to Hevder's nose breathing case (see Table D2) which yields nasal deposition of 3.5c%e and deposition in the alveolar region of the lUng of 13:04c. The model predicts zero deposition for both the mouth,throat and the tracheo-bronchial regions. From the depositiomcurves of Gerrity er aG (1979) (Fig. 2) for iron oxide extrapolated to a particle size of 0.25 µm.(which is eq uivalent to an aerodynamic diameter of 0.4 µm ) it appears that all of the lung deposition from passive smoking probably occurs deep in the alveolar region at generation 19 or beyond. Black and Pritchard (1984) have determined the half-time for alveolar retention for direct cigarette smoke to be 17 hours indicating that the smoke particles dissolve and clear into the blood or lymph system. There is every reason to believe that the passive smoke particles clear the same way. With direct smoking there has so far been no model de- veloped'that explains the observed phenomena, namely that the inhaled particle size is about 0.7' µm, that 70% to 809c of the inhaled smoke is retained, that 15 to 359'e is retained in the mouth, and that the exhaled~panicle size is also about 0.7 µm; The Heyder modeli at 0l7 µm, would predict total retentiomof only 12%. To achieve 75% retention, the Heyder model would require an effective particle size of 6.5 µm, Main streamismoke is knowmto agglomerate. but if it agglomerated to 6.5 µm, the exhaled' smoke. according to the He.der modeli, would be about 6 µm, much too, large compared to that observed. Mitchell (1962) observed that direct smoke particles grow in the mouth to about 1.15~µmi and that the smoke exhaled from the lung after a S second retention period had a mass median diameter size of 0.65 µm. Let us assume that the 0.65 µm part of'the smoke follows Hevder's model an&thar209c of the total smoke inhaled was exhaled', all from the 0;65 µm fraction. The inhaled part of the smoke corre- sponding with the 0.65 µm part exhaled would have the same particle size and would deposit about 12%. deep in the al- veolar region.. This is 1'217c of 22.7ro of the total smoke in- haled'~ or 2.7% of the total inhaled smoke. The balance of the inhaled smoke (77%) would have a larger average particle size„about 1.3 µm. Black and Pritchard (198-1)lfound. based on clearance data, thatthe rates of alveolar c+eposition to alveolar plus tracheo-bronchial deposition, in, direct smoking is 0.36. Also, as noted, some amount, say 25% of the total inlet smoke should deposit in the mouth and throat. all of which would have to come from thislarger size fraction.,Sum- marizing these numbers, of the 100 -'0 -'5 = 55cc of total smoke particulate that reaches the lun¢ and is non ex- haled, 0~64 x 55, = 35% deposits in the tracheo•bronchial region and 0.3& x 55 = 20% deposits in the alveolar region, We have already accounted for 3% of the alveolar deposition from the 0:65 µm particles. The remaining 17% would come from the largerparticles.,Based on the alveolar/tracheo-bron- chial split and using the curves of Gerrity er al: (1979) it would be expected that about 2/3 of the alveolar deposit or l1,rr, would deposit in the "near° alveolar region, generations 16- 18, and 6% in the "deep" alveolar region., generations 19- 21, for a total "deep" alveolar deposition of 9%. These cal- culations are summarized in Table D3. Just what the mechanisms are for so much direct smoke deposition remains unclear. Certainly impaction and sedi- mentatiom(thc Heyder model) do not account for it. Stober (196-t)isuggests that electricallcharges in the newly generated smoke particles (see Melandri er al:, 1983) mav aceounv for some of it. Another possible mechanism is the cloud settling phenomenon as described by Fuchs(196J). Whatever the mechanism, a reasonably clear idea of the regionalI deposition patterns from direct and passive smoking

Adult mortalirkfnm passn•e smoking can be obtained as shown in Table D3. The nasal deposition from passive smoking could account for the observed nasal sinus cancer. Also. if the observation of Balin er aL (1986) is correct that there is a direct passage for toxics from the nose to~ the brain, it could also account for the observed brainn cancer. Ih the deep alveolar region the ratio of direet to pas- :h` sive deposition is much closer to the inhaled'ratio ~than to the "total retained" ratio. It is from the deep alveolar region thac the smoke particles are solubilized and clearedGnto the blbo& and lymph systems possibly to cause cancers of the liver, breast and endocrine glands, leukemia. h•mphoma and ar- terial plaques.