SRE/AIW/18.4.74 DARK TOBACCO CIGARETTES Summary Although a number of studies have been undertaken, there is relatively little information on dark tobacco cigarettes. Apart from the interest in cigar tobaccos, this may be partly due to the local 'native' nature of dark tobaccos, which are often produced from local, or locally naturalised, seed lines. Mouse-skin studies show that condensate from dark tobaccos, including cigar tobacco manufactured into cigarettes, are at least as tumorigenic and often more tumorigenic than that from flue-cured Burley and oriental tobaccos. Following a long-term inhalation experiment, assessed on the basis of the severity of laryngeal lesions in hamsters, Dontenwill concluded that smcke from a "black" cigarette was biologically very much less active than smoke from the reference cigarette; the latter being a 'standard' German blend. It should be noted, however, that the reduction in biological activity could be accounted for almost e-.ntirelv by a lower accumulated dose from the "black" cigarette due to a shorter exposure time 'and the lower delivery of smoke. A similar reason may also be advanced for the marked reductions found for filter tip versions of the reference blend. Because of the publicity which has surrounded the work of Passey and his colleagues, this must also be included in a bonsideration of dark tobacco cigarettes. Nevertheless, the studies, which were undertaken under poor experimental conditions, have been severely criticised and do not add materially to our knowledge of dark tobacco cigarettes. In conclusion, the hypothesis that smoke from dark cigarettes is "safer" than that from flue-cured or blended cigarettes is certainly not supported by the results of the mouse-skin painting experiments and the Dontenwill inhalation study appears to provide only shaky supporting evidence. On the present evidence, it is 1~; suggested that any concept of a lower risk attached to dark C:) cigarettes canr in a given population, only be associated with a reduced level of inhalation faccuumulated dose) from such products. r\-) BATCo document for Province of British Columbia 2 November 1999 DARK TOBACCO CIGARETTES a) . Study of Ciqar Tobacco Condensate Following reports from Croninger (1) and Homburger (2), which suggested, but did not prove statistically, that cigar smoke condensate was more carcinogenic than that from cigarette smoke, Davies and Day (3) re-examined the position. The results obtained after 116 weeks showed that the condensate from the cigar was more carcinogenic than that of the cicarette manufactured from cigar tobacco or from flue-cured tobacco. There was no significant difference in carcinogenicity to mouse-skin of the condensates from the two cigarettes. The differences in mortality rates were small and the results were not affected by age-standardisation. b) Comparison of Tobacco Types In a further TRC experiment, a number of different types of tobacco, including an air-cured fermented (Paraguay) tobacco, --yere examined. The tumorigenic ratios and 95% confidence limits for the condensates from the various cigarettes compared with the flue-cured "control" (T4) were: SaiPple T16 Air-cured fermented 1.38 (1.14 - 1.65) T17 Burley 1.07 (0.89 - 1.29) T18 Oriental 1.11 (0.92 - 1.33) T19 indian sun-cured 1.55 (1.29 - 1.90) T20 Indian flue-cured 1.22 (1.02 - 1.47) These results show that condensate fro-m air-cured fermented tobacco is more tumorigenic than the flue-cured control. Condensate from Indian sun-cured is also more tumorigenic, while that from Indian flue-cured tobacco is just significantly more tumorigenic than the control. The differences for Burley and Oriental tobaccos are not significant. Subsequently, Imperial Tobacco Ltd. have compared condensates from Gauloises and other continental brands with Embassy cigarettes. Full details are not available, but at 92 weeks, it was clear that condensate from Gauloises Caporal plain CD CD 110 NJ CD BATCo document for Province of BritiSh Columbia 2 November 1999 -2- was very much more tumorigenic than that of Embassy filter. The ranking was : Gauloises'> Belga Rouge -filter > Nazionali Esportazione Embassy c) Inhalation Study Dontenivill et al. (4) In this long-term experiment, smoke from a "black" cigarette manufactured from a blend of Burley (15%), Maryland (6%), and dark tobaccos was compared with a "standard" German blend and various other cigarettes. Comparison of the various cigarettes was based on the seveje laryngeal changes found following exposure of hamsters to 30 cigarettes twice a day for up to two years. On this basis, smoke from the "black" cigarette was found to have only 33% (stage 5) or 12% (stage 6) of the activity of the reference cigarette, ie. a 67-88% reduction in activity . Apart from the absence of suitable methods for the analysis of such experiments, two main fac-,~crs should be considered in attempting to put these reslilts into perspective. 1. Cellulose acetate cr paper filter versions of the reference cigarette also led to a cunsiderable reduction in activity; 56-60% (stage 5) and 76-99% (stage 6) respectively. 2. The condensate from the "black" cigarette was nearly 40% lower than that from the reference cigarette and the exposure time was also 20% lowe:c. Similarly, condensate deliveries from the filter cigarettes were 30 and 33% lower than that of the reference ciaarette. Since the above reduction in condensate delivery and exposure tiine for the "black" cigarette compared with the re-Eerence cigarette obviously reduce the total accumulated dose to the respiratory system, it is considered that the mar!-ed reduction in biological response should be treated with considerablg=' caution. BATCo document for Province of British Columbia 2 November 1999 -3- Other Inhalation Studies Passey et al. (5) In two experiments, groups of 12 rats were exposed to smoke under what can only be considered ;,.s poc.,- experimental conditions. In one experiment, cigarette smoke .:as compared with smoke from cigarettes manufactured from cigar tobacco (TRC C2). A commercial cigar tobacco cigarette (Calypso) and a cigarette manufactured from Burley tobacco (TRC T17) were included in the second experiment. The rats exposed to smoke from flue-cured tobacco died early and with enlarged and severely diseased lungs. The conclusions drawnwere that smoke from flue-cured . cigarettes is more dangerous to man and to animals than that from air-cured tobaccos and that this is related to the method of curing (and the sugar content) of the tobaccos. These experiments have been criticised severely because the pathological findings of the rats which died suddenly could be related to an inflammatory condition not regularly encountered in man: Passey himself stated that chronic respiratory disease and bronchiectasis were endemic in the strain of rats used Zor their studies. Passey also undertook some limited mouse-skin painting experiments. Passey's studies have become linked to lung cancer (because of a limited mouse-skin study) and also to a theory of lung cancer induction advanced by Braven and Fenner M: the lattcr because of Passay's contention that the sugar conLe-nt of the tobacco was an important factor. In the same review (6), it is argued that, although the studies of Passey may conceivably have some relevance to chronic inflammatory lung disease in man, there are no grounds for regarding them as relevant to lung cancer. The link with sugar content and Braven and Fenner's work is also criticised, since there is no evidence that cystein offers protection from cancer iniucing effects of chemical agents. SRE/AIW/19.4.74 %) NJ N-) BATCo document for Province of BritiSh Columbia 2 November 1999 1 . Croninger, A.B. et al. 2. Homburger, F. et al 3. Davies R.F. et al. 4. Donten-dill, W. et al. 5. Passey, R.D. et al 6. Editorial 7. Braven, J. et al. 8. Fenner, M.L. et al. Cancer ReL. 1956. 18, 1263 J. Natn. Cancer Inst. 1963, 31, 1445 Br. J. Cancer, 1969, 23, 363 J. Natn. Cancer Inst. 1973, 51, 1781 Br. med. J. 1971, IV, 198 Lancet, 1973, 187 Br. J. Cancer, 1967, 21, 623 Br. J. Cancer, 1968, 22, 474 C-D CD -0 110 BATCo document for Province of BritiSh Columbia 2 November 1999 APPENDIX Details of Cigarettes and Cig-ars used in TRC Cigar Study Table 1 Code L,~ngth Circum Weight I Butt Puff NVWSC (4) Leng Lin No. (mm) (mm) (g) (mm) (mg) CIM 83 33.7 1.86 25 19.8 37.8 C2(1) 70 25.1 0.94 20 8.4 19.4 T4 (3 70 25.3 1.09 20 10.9 26.3 (1) Composite blend cigar tobacco; granulated wrapper and binder of natural leaf. (2) Blend as C1 cut at 50 cpi for cigarette manufacture (3) Composite blend of flue-cured tobacco. (4) Non volatile whole smoke condensate. :zmoking conditions : Duff volume 25 ml duration 2 seconds one puff per minute Table 2 Summary of results from Dontenwill Inhalation Study Sample Condensate Relative Laryngeal Changes ExDosure Relative Potency Factor Dry Factor Stage 5 Stage 6 (mg/cig) Ccntrol (1) 33.7 1.0 1.0 1.0 1.0 "Black" (2) 20.9 0.62 0.8 0.33 0.12 Control 23.5 0.70 1.0 0.44 0.06 Acetate Filter Control 22.7 0.67 1.1 0.40 0.24 Paper Filter (1) German blend: 551. flue-cured, 35% oriental and 10% Burley (2) Black cigarette: 15% Burley, 6% Maryland, 6% Java, 19% cigar tobacco, 54% other dark tobacco (-n BATCo document for Province of British Columbia 2 November 1999