WDEUBTtyl/46D I November 1989 CARCINOGENS IN TOBACCO This review has been based on the summary of information provided in the 1989 US Surgeon General's report, "Reducing the health consequences of smoking - 25 years of progress". Where necessary reference has been made to the probable sources of the data in view Of Sortie apparent errors in the levels quoted. In addition, it should also be understood Iha( the use of the term "carcinogen" in this context should be qualified. It is not surprising that in view of the 2500 + compounds so far identified in tobacco, a few should be found to be carcinogenic when administered in isolation in experimental animals. Many substances have been designated as carcinogens under such conditions, but for only a very small proportion has this finding been generally agreed to be relevant to human experience. Although a substantial number of carcinogenic substances has been identified in tobacco smoke. relatively few have been found in tobacco. It follows that the majority of tobacco smoke carcinogens are formed by combustion/pyrolysis inechanisms when tobacco is smoked as cigarettes or other smoking articles. A recent summary of carcinogens found in tobacco and Mainstream cigarette smoke is given in Table 7 of the attached sectionof a prepublication version of the U.S. Surgeon General's 1989 report. Table 7 illustrates the point made in the previous paragraph, for example the listed polycyclic aromatic hydrocarbons (PAPI) do not occur naturally in tobacco or other plant materials, but are formed when these are burned. The source references for the data in Table 7 are not given, but it is likely that tile quoted 0.1 - 90 ng per gram range for tobacco benzo (a) pyrene (13P) refers to results for U.S. snuff brands, see Table I of the allached paper by Hoffmann et al (JNCl, 79. 1281-1286. 1987). The authors comment that during the processing of snuff, especially during curing, the tobacco can be contaminated with traces of PAH. In another paper by these authors (JNCI, 76, 435-437. 1986) this contamination is attributed to fire-curing or flue-curing. The former seems more likely, becausp during fire-curing tobacco comes into direct contact with wood smoke. Titus for tobacco ptepared by the more common air and flue-curing methods, BP levels are likely to be very low, subject only to air pollution. N-nitrosamines are found in cured tobacco at levels which vary widely depending on tobacco type, curing process and subsequent tobacco treatments. The Surgeon General's data again seerns to reflect snuff values as indicated by results ill the attached paper "N-nitrosaniines in tobacco caicinogeilesis" (Banbury Report 12, 1982). Generally, lower levels are found in cigarette tobaccos as shown by the attached table, "Table 1 N-nitrosamines in commercial tobacco products" taken from page 748 of CD C) "N-nitroso compounds: occurrence, biological effects and relevance to human cancer" 110 co CYN 00 C711 BATCO document for Province of BritiSh Columbia 28 October 1999 published by (lie IARC, 1984. Note also that both tile Baribury and IARC references givedata for anotherN-nitrosamirie, N-nitrosoarialabine (NAT) riot listed bythe Surgeon General. The Banbury paper (page 219) also contains the statement:- *Our major interest in the tobacco-specific nitrosamines is based on the fact that these compounds are the only known organic carcinogens in processed tobacco . ...... However, the later Surgeon General's report also records three aldellydes, 1,1,-dimethylhydrazine and ethyl carbaniate in Table 7. The aidehyde data are once again derived from snuff samples and [fie JNCI 1907 reference discussed earlier. From that reference it is clear that tile acetaldellyde results are in units of pg/gram, not mg/gram as given by the Surgeon General's report. Generally the literature has paid little attention to the levels of these substances in tobacco probably because of [tie higher levels in tobacco SITloke. The 1, 1 -dinietllylhydrazine data in the Surgeon General's report are taken from a paper bySchmeltzetal. (Cancer Letters, 2,125-132,1977). However, based on the original reference the units should be ng/graf7i, not pg/gram. A U.S. commercial blend and a flue-cured Virginia tobacco gave levels of 60 and 147 ng/gram respectively. The Surgeon General's table does not include the result for a Burley tobacco - none was detected. The ethyl carbarnate results in the Surgeon General's Table 7 also originate with Schmeltz et at (Journal of Analytical Toxicology, 2. 265-268, 1978). Two samples of Burley leaf, with and without maleic hydrazide treatment, gave results of 310 and 375 ng/grain respectively. Table 7 of the Surgeon General's report also cites seven inorganic "compounds". Hydrazine results have probably been taken from a paper by Hecht el at (DHEW Publication No. (NIH) 76-1221, pages 191-202, 1976). Maleic hydrazide treated Burley tobacco gave the highest level (51 ng/cigarette) compared to 22 ng/cigarette for untreated, hand-suckered Burley tobacco. (Maleic hydrazide is an anti-suckering agent). Treated and untreated flue-cured tobaccos showed no difference in hydrazine content (12 and 14 ng respectively). A U.S. Commercial cigarette contained 30 ng. Table IV of the same reference quotes tobacco level ranges for arsenic, nickel, chromium, cadmium, lead and polonium-21 0 which in most cases are of tile same order of magnitude as those cited by the Surgeon General. The latter's polonium-21 0 range is probably taken from snuff samples analysed by Hoffmann et al, see Table I of the 1987 JNCI paper cited earlier. C:) %10 c0 0 I. 00 C11 4-PI BATCo document for Province of BritiSh Columbia 28 October 1999 Finally, it should be noted that with over 2,550 known compounds in unadulterated tobacco (see the extract from the Surgeon General's report) and with variable criteria for demonstration of a substance's carcinogenicity, it is not possible to produce a definitive list on this subject. The attached Table 7 of the Surgeon General's report is, however, a very recent attempt to do this and has been used as the central basis of this note. ,~, 1) 1 )-- W.D.E. Irwin C~p 1.0 Co 01% cc C7% Cr% BATCO doCuMent for Province of BritiSh COIUMbia 28 October 1999