Scholarly article on topic 'Influence of cigarette circumference on smoke chemistry, biological activity, and smoking behaviour'

Influence of cigarette circumference on smoke chemistry, biological activity, and smoking behaviour Academic research paper on "Chemical sciences"

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{Cigarette / Circumference / Smoulder / "Smoke yields" / Bioactivity / Formaldehyde / Slim}

Abstract of research paper on Chemical sciences, author of scientific article — Kevin McAdam, Alison Eldridge, Ian M. Fearon, Chuan Liu, Andrew Manson, et al.

Abstract Cigarettes with reduced circumference are increasingly popular in some countries, hence it is important to understand the effects of circumference reduction on their burning behaviour, smoke chemistry and bioactivity. Reducing circumference reduces tobacco mass burn rate, puff count and static burn time, and increases draw resistance and rod length burned during puff and smoulder periods. Smoulder temperature increases with decreasing circumference, but with no discernible effect on cigarette ignition propensity during a standard test. At constant packing density, mainstream (MS) and sidestream (SS) tar and nicotine yields decrease approximately linearly with decreasing circumference, as do the majority of smoke toxicants. However, volatile aldehydes, particularly formaldehyde, show a distinctly non-linear relationship with circumference and increases in the ratios of aldehydes to tar and nicotine have been observed as the circumference decreases. Mutagenic, cytotoxic and tumorigenic specific activities of smoke condensates (i.e. per unit weight of condensate) decrease as circumference decreases. Recent studies suggest that there is no statistical difference in mouth-level exposure to tar and nicotine among smokers of cigarettes with different circumferences. Commercially available slim cigarettes usually have changes in other cigarette design features compared with cigarettes with standard circumference, so it is difficult to isolate the effect of circumference on the properties of commercial products. However, available data shows that changes in cigarette circumference offer no discernible change to the harm associated with smoking.

Academic research paper on topic "Influence of cigarette circumference on smoke chemistry, biological activity, and smoking behaviour"

Accepted Manuscript

Influence of cigarette circumference on smoke chemistry, biological activity, and smoking behaviour

Kevin McAdam, Alison Eldridge, Ian M. Fearon, Chuan Liu, Andrew Manson, James Murphy, Andrew Porter

PII: S0273-2300(16)30258-6

DOI: 10.1016/j.yrtph.2016.09.010

Reference: YRTPH 3670

To appear in: Regulatory Toxicology and Pharmacology

Received Date: 28 July 2016 Revised Date: 8 September 2016 Accepted Date: 11 September 2016

Please cite this article as: McAdam, K., Eldridge, A., Fearon, I.M., Liu, C., Manson, A., Murphy, J., Porter, A., Influence of cigarette circumference on smoke chemistry, biological activity, and smoking behaviour, Regulatory Toxicology and Pharmacology (2016), doi: 10.1016/j.yrtph.2016.09.010.

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1 Influence of cigarette circumference on smoke chemistry,

2 biological activity, and smoking behaviour

4 Authors: Kevin McAdam13, Alison Eldridge1, Ian M. Fearon1, Chuan Liu1, Andrew

5 Manson1, James Murphy1, Andrew Porter2,

7 1 Group Research & Development, British American Tobacco (BAT), Regents Park

8 Road, Southampton SO15 8TL, UK.

9 2 3810 Saint Antoine West, Montreal, QC, Canada

10 3 Corresponding author:

12 Abstract

13 Cigarettes with reduced circumference are increasingly popular in some countries,

14 hence it is important to understand the effects of circumference reduction on their

15 burning behaviour, smoke chemistry and bioactivity. Reducing circumference reduces

16 tobacco mass burn rate, puff count and static burn time, and increases draw resistance

17 and rod length burned during puff and smoulder periods. Smoulder temperature

18 increases with decreasing circumference, but with no discernible effect on cigarette

19 ignition propensity during a standard test. At constant packing density, mainstream (MS)

20 and sidestream (SS) tar and nicotine yields decrease approximately linearly with

21 decreasing circumference, as do the majority of smoke toxicants. However, volatile

22 aldehydes, particularly formaldehyde, show a distinctly non-linear relationship with

23 circumference and increases in the ratios of aldehydes to tar and nicotine have been

24 observed as the circumference decreases. Mutagenic, cytotoxic and tumorigenic

25 specific activities of smoke condensates (i.e. per unit weight of condensate) decrease as

26 circumference decreases. Recent studies suggest that there is no statistical difference in

27 mouth-level exposure to tar and nicotine among smokers of cigarettes with different

28 circumferences. Commercially available slim cigarettes usually have changes in other

29 cigarette design features compared with cigarettes with standard circumference, so it is

30 difficult to isolate the effect of circumference on the properties of commercial products.

31 However, available data shows that changes in cigarette circumference offer no

32 discernible change to the harm associated with smoking.

34 Keywords:

35 Cigarette, circumference, smoulder, smoke yields, bioactivity, formaldehyde, slim

37 1. Introduction

38 Although cigarette rods are generally cylindrical in shape they can, and have, been

39 made in a variety of lengths and circumferences. Reasons for adopting different

40 dimensions include cost, marketing objectives and government regulations. However

41 changing the cigarette dimensions may affect the smoke formation and transport

42 processes within the cigarette rod which in turn could affect the yields of both

43 mainstream (MS) and sidestream (SS) smoke (Norman 1999). There are also potential

44 changes to the composition of the smoke which can affect its specific biological activity,

45 which is the activity per unit weight of the smoke or one of its components such as

46 nicotine. Understanding these relationships is important both when interpreting chemical

47 and biological assays associated with circumference changes and in understanding

48 smoker behaviour or smoker perception studies.

49 Although experimental cigarettes have been made with circumferences ranging from as

50 low as 10 mm up to 70 mm (Perfetti & Norman, 1986; Luke, 1986; Norman et al., 1988;

51 Lewis, 1989; White & Perfetti, 1992), the dimensions of commercial products are limited

52 by cigarette manufacturing machine constraints, product performance standards and

53 consumer acceptability. Traditional king size cigarettes have circumferences of 24 to 25

54 mm, while slimmer styles of cigarette can have circumferences that range from 14 to 24

55 mm. While the nomenclature is not standardised, cigarettes with circumferences

56 between 21 and 23 mm are often termed "slim", those between 19 and 21 mm are

57 referred to as demi-slims and those in the range 14 to 19 mm are termed "super slim".

58 There are also a few "wide" cigarettes on the market with circumferences of 27 to 28

59 mm, which are considerably larger than traditional king size cigarettes. Cigarettes of

60 different circumference can be made with or without filters and are generally found

61 commercially in lengths of 80 to 85 mm, 90 to 100 mm and 120 mm.

62 Reduced circumference cigarettes have been marketed for well over sixty years. Early

63 examples include the plain end and filter versions of the Homa cigarette brand which

64 were first produced by the Iranian Tobacco Company in the early 1950s and 1960s,

65 respectively, and had circumferences of 19.75 mm (Reemstma, 1987). In 1973 Lugton

66 (1973) described a large number of commercial brands from around the world including

67 Players No 6 Filter, marketed as a lower cost alternative brand in the UK with a total

68 length of 66 mm and a circumference of 23.2 mm, as well as plain-end cigarettes from

69 Kenya with even lower circumferences: 21.9 mm for King Stork, 20.8 mm for Crescent

70 and Star and 18.1 mm for Ten Cents. Samfield (1991) described an Egyptian brand,

71 King George V from the mid-1950s, with a circumference of 17.4 mm.

72 In the US, Virginia Slims with a circumference of 23 mm and a length of 100 mm were

73 introduced in 1968, and the first brand marketed as a "super slim", Capri, was launched

74 in 1987 and had a circumference of 17 mm.

75 Currently, reduced circumference cigarette products are becoming more popular in

76 certain areas of the world. Markets with the highest share of slim products are South

77 Korea, Indonesia, Kazakhstan and Iran where they are predominantly smoked by adult

78 males (Park, 2009). In the European Union, research by the European Commission has

79 shown that the market share of reduced circumference cigarettes grew significantly

80 within a declining EU cigarette market from ~3.6% in 2006 to ~6 % in 2012 (EC, 2013).

81 This is consistent with global trends where sales of reduced circumference cigarettes

82 have been reported to have grown ten times faster than the overall market in the past

83 five years (EC, 2013). The lack of association between smoking prevalence rates and

84 market share of slim (<7.5 mm diameter, <23.6 mm circumference) cigarettes has been

85 confirmed by studies of smoking data in up to 96 countries for the years 1996, 2006 and

86 2012 (Slater 2016). After accounting for socio-economic and cultural confounding

87 factors, the correlation between smoking prevalence and market share of slim cigarettes

88 for males was only significant (at P<0.1) for one of the years (2012), and, for females,

89 there were no significant correlations for any of the years.

90 Given the increasing interest in slim circumference cigarettes, this review examines the

91 effects of changing cigarette circumference on cigarette physical properties, burn rates,

92 combustion temperatures, MS and SS smoke chemistry, smoke toxicity and smoking

93 behaviour. In this review we have made use of both peer-reviewed papers published in

94 the open literature as well as unpublished tobacco industry documents, sourced from the

95 Legacy Documents database. Also note that all the unpublished industry documents

96 (except a reference to Mouth Level Exposures on the BAT website) can be easily

97 identified since they include a link to the Legacy website and the link is always preceded

98 by "industry documents" or "legacy".

99 The review focuses mainly on the effects of circumference change alone, so that the

100 influence of confounding design variables can be avoided. These data are mostly

101 available from experimental studies performed by tobacco industry laboratories in which

102 series of cigarettes with only changes in circumference were designed and tested.

103 However commercial, low circumference cigarettes are designed to be acceptable to

104 smokers and other design features such as levels of filter ventilation, tobacco packing

105 density or paper porosity may also change. It is beyond the scope of this review to

106 assess the interaction of other variables with circumference on, for example, smoke

107 chemistry or bioactivity. However some studies of smoke toxicants from commercial low

108 circumference cigarettes are also reviewed in section 9.3.

109 Historically, the effects of cigarette rod circumference have been well studied (e.g.

110 Arany-Fuzessery et al., 1982; Gugan, 1966; Muramatsu, 1981 & 2005; Resnick et al.,

111 1977; Yamamoto, 1981) with the first investigations, which focused on nicotine yields,

112 dating back to 1936 (Wenusch, 1936). Further research coincided with the

113 commercialisation of lower circumference cigarettes in the 1950s, and with the

114 introduction of the Cigarette Safety Act in the mid-1980s when cigarette circumference

115 was one of the variables studied in attempts to understand ignition propensity of

116 cigarettes. A new phase, currently ongoing, involves analysing market trends towards

117 slimmer cigarettes, as well as research into reduced toxicant prototype cigarettes

118 (Dittrich et al., 2014). In reference to the latter aspect, reducing circumference has been

119 one of a number of cigarette design parameters that have been investigated as a

120 potential route towards harm reduction.

121 122 123

124 2. Physical properties of the cigarette

125 Circumference is one of several variables that can be altered during cigarette design

126 and, as will be seen in this review, it has an impact on cigarette physical properties as

127 well as smoke chemistry and bioactivity.

128 There are two major physical changes that occur when cigarette circumference is

129 reduced. The first, perhaps self-evident, is that at a constant packing density (the

130 density of tobacco in the cigarette rod) and tobacco rod length, the tobacco weight is

131 reduced in proportion to the volume reduction, or cross-sectional area. The second is

132 that resistance to draw, or pressure drop, increases in inverse proportion to the reduced

133 cross-sectional area at a constant volumetric flow. In mathematical terms the pressure

134 drop along a tobacco rod can be described (Schneider & Schluter, 1984) by a modified

135 Kozeny-Carman equation (Carman, 1956). The Kozeny-Carman equation is used in the

136 field of fluid dynamics to calculate the pressure drop of a fluid flowing through a packed

137 bed of solids under lamina flow. For a tobacco rod the equation can be written as:

140 Where A'is an empirical factor related to the tobacco particle shape and tortuosity of the

141 spaces between the particles, ^is the flow rate of air drawn through the rod, A is the

142 cross-sectional area of the cigarette, C is the circumference, pp is the packing density

143 and pt is the density of the tobacco shreds.

144 The equation shows that pressure drop is inversely proportional to the cross sectional

145 area, or square of circumference, and it is also very sensitive to the packing density of

146 the blend, pp. Several authors (Norman, 1999; Hook, 1985) have pointed out that many

147 of the early studies of the effects of circumference change either failed to adequately

PB = Kjfptf($?/{! -

148 control packing density (e.g. Wenusch, 1936), or deliberately altered packing density to

149 obtain a constant pressure drop. Since pressure drop affects ventilation into the smoke

150 stream through the paper or filter as well as the filtration of smoke particulate along the

151 rod (Norman, 1999) some of the early studies relating cigarette circumference to other

152 cigarette physical properties and smoke yields may not be reliable.

153 3. Burn rate and puff number

154 The smouldering and puffing processes in a burning cigarette have been studied

155 extensively and have been comprehensively reviewed (Baker, 1981 & 1999). During

156 free smoulder, cigarette combustion is maintained by diffusion of oxygen through the

157 charred burn-line zone of the cigarette paper into the back of the burning coal as shown

158 in Figure 1a. As the circumference is reduced and the tobacco weight per unit rod length

159 decreases, the smoulder rate is affected: the rate at which the length of tobacco rod is

160 consumed ("linear burn rate") increases while the rate at which tobacco is consumed

161 ("mass burn rate") is reduced (Ivinson, 1962; Rice, 1968; Rice et al., 1970; Lugton, 1971;

162 Resnik et al., 1977; Muramatsu, 1981; Perfetti et al., 1983; Arany-Fuzessery, 1982).

163 This is illustrated in Figure 2 which shows the linear and mass burn rates for tobacco

164 rods with circumferences ranging from 19-31 mm (Lugton, 1971). Over this range of

165 circumferences the linear burn rate is inversely proportional to the circumference while

166 the mass burn rate is directly proportional to the circumference.

167 Yi et al. (2001) developed a semi-empirical mathematical model to describe free-

168 smouldering behaviour of cigarettes. Their results for mass and linear burn rates were in

169 good agreement with experimental values obtained by Rice et al. (1970) and Resnik et

170 al. (1977). Their model also showed that mass burn rate was more sensitive to changes

171 in circumference than changes in packing density, as also found experimentally.

172 During puffing, air is drawn along the tobacco rod and through the coal (Figure 1b). At

173 the start of the puff the coal temperature increases rapidly, from about 600°C to greater

174 than 900°C, which causes the impedance to gas flow within the coal to increase. As the

175 puff proceeds, air tends to preferentially enter the burning zone of the cigarette behind

176 the paper burn line where the draw resistance is lowest (Baker, 1999). The exothermic

177 combustion of tobacco in this region causes the periphery of the tobacco rod to burn

178 down more rapidly than the central zone, resulting in an elongated coal section. At the

179 end of the puff, the periphery cools quickly and the paper burn line stops advancing. At

180 the same time the centre of the coal advances more rapidly until the coal resumes its

181 initial shape. The time between the end of the puff and the re-establishment of the coal

182 shape may take 15-20 seconds (Li et al., 2016).

183 There have been several studies of burn rates during puffing (Egerton et al., 1963;

184 Resnik, 1977; Yamamoto, 1981; Muramatsu, 1981; Perfetti et al., 1983). All the studies

185 showed that under puffing conditions decreasing the circumference of the cigarette at

186 constant tobacco density decreases the volume (and therefore mass) of tobacco

187 consumed during the puff and during the inter-puff smoulder period. Yamamoto (1981)

188 for example measured weight losses during puffing for a series of unfiltered tobacco

189 rods with circumferences in the range 20.5-27.0 mm. As the circumference decreased

190 the weight losses also decreased. Muramatsu (1981) measured the linear burn rates

191 during smoking of unfiltered tobacco rods with constant packing density and

192 circumferences ranging from 20.3 to 26.1 mm. Linear burn rates during puffing were

193 about 20 times faster than during free smoulder, while between puffs the smoulder rates

194 were about 20% slower on average than with a cigarette smouldering in a non-puffed

195 experiment. The length burned during puffing (2 second puffs) was, on average, about

196 18% greater than that between puffs (58s intervals).

197 Perfetti et al. (1983) measured burn rates during the puff and during the inter-puff

198 smoulder period. Unfiltered tobacco rods, with circumferences of 21.5 to 24.7 mm, were

199 each smoked at three puff volumes (20, 35, and 65 mL) for a 2-second duration

200 corresponding to flow rates of 10, 17.5 and 32.5 mL/s. The length of tobacco rod burned

201 during the puff increased linearly with decreasing circumference. There was a 10%

202 increase in the rod length burned per puff for the 21.5 mm rod compared with the 24.7

203 mm rod. The cross-sectional area decreased by 33% for the 21.5 mm rod compared

204 with the 24.7 mm rod, while the actual weight of tobacco burned during the puff

205 decreased by approximately 20%. Perfetti et al. also showed that increasing puff

206 volume increased the puff burn rates to a similar extent at each rod circumference, but

207 the extent of change was not proportional to the increase in puff volume. They observed

208 that with a 65 mL puff volume, and particularly for smaller circumference cigarettes, the

209 cigarette paper at the char line and along the whole length of the rod visibly constricts

210 during a puff and then relaxes afterwards. With larger puff volumes, it is likely that

211 increased proportions of the incoming air will by-pass the burning zone and enter

212 through the cigarette paper. These observations and proposed mechanism are

213 consistent with the lack of proportionality between the increase in rod length burned

214 during the puff and the increase in puff volume.

215 The rod length and weight of tobacco burned during the puff may also be influenced by

216 the extent of peripheral heat loss. Greater peripheral heat loss from smaller

217 circumference tobacco rods is expected due to the greater surface area-to-volume ratio.

218 The faster linear burn rate which occurs with decreasing circumference also leads to a

219 decrease in puff number. Baker (1973) reviewed several studies of the effect of

220 circumference on puff number and these showed that puff number was directly

221 proportional to the weight of tobacco in the cigarette (Figure 3) or, at constant packing

222 density, to the cross sectional area. Irwin (1988a) also showed that puff number was

223 proportional to the tobacco weight burned for cigarettes with circumferences in the range

224 of 13 to 29 mm. Baker and Irwin's data therefore showed a good correlation between

225 the square of the circumference and the puff number. In contrast, Yamamoto (1984)

226 showed that over a limited range of circumferences (21-26 mm) the puff number was

227 directly proportional to the circumference. However in this relatively narrow range of

228 circumference Yamamoto's data also correlates equally well with the square of

229 circumference.

230 4. Combustion temperatures

231 Based on the increase in formation rates of CO and HCN at low circumferences,

232 Yamamoto (1985) speculated that the puffing temperature increased with decreasing

233 circumference. However, this was not supported by the experiments of Robinson (1985)

234 and Irwin (1988a).

235 Robinson (1985) measured coal surface temperature distributions during puffing and

236 smouldering using a scanning infra-red thermovision system. Plain cigarettes with

237 circumferences of 13, 20 and 29 mm, at constant packing density, were compared in this

238 study. The peak smoulder temperatures increased linearly (by 80°C) as the

239 circumference decreased from 29 to 13 mm. The peak puffing temperatures increased

240 from 889°C for the 29 mm cigarette to 903°C for the 20 mm cigarette, but dropped to

241 851C for the 13 mm cigarette , . It was speculated that a low peak puff temperature

242 would be expected at higher circumferences as the air flow is spread over a larger cross

243 sectional area and the burn behaviour more closely approaches the smouldering state.

244 Robinson suggested that the reduction in peak puffing temperature for the 13 mm

245 cigarette was due to a higher proportion of the puff passing through the burning coal

246 rather than through the paper at the periphery of the combustion zone, suggesting

247 different combustion conditions for this sample.

248 Coal surface temperatures were also reported by Irwin (1988a) for plain end cigarettes

249 with circumferences of 13, 17, 20, 22, 24.75 and 29 mm. Smoulder temperatures

250 increased linearly (by 95°C) as the circumference d ecreased from 29 to 13 mm. The

251 peak puffing temperatures for the 13 and 29 mm circumference cigarettes were not

252 significantly different from each other but were significantly lower than those for the 17253 24.75 mm circumference cigarettes. This followed the same pattern observed by

254 Robinson in the previous study (Robinson, 1985). However Irwin noted that the length of

255 the coal increased as the circumference decreased from which one could conclude that

256 more air enters the burning zone through the periphery of the burning zone rather than

257 through the coal as suggested by Robinson (1985).

258 5. Cigarette ignition propensity

259 The smouldering properties of cigarettes would also be expected to affect their ignition

260 propensities. The science behind reduced ignition propensity cigarettes was recently

261 reviewed by Baker et al. (2016). Early studies to relate cigarette structural parameters to

262 their tendency to ignite furniture fabrics were conducted by the Center for Fire Research

263 (National Bureau of Standards, Washington, D.C.). Using a test system consisting of a

264 bench scale furniture mock up and 32 test cigarettes with different construction

265 parameters, it was found that reducing tobacco density, paper porosity and

266 circumference (21 mm vs 25 mm) caused a reduction in ignition proclivity (Gann et al.,

267 1987, Krasny et al., 1989). It was thought that reducing circumference was effective

268 because it reduced the weight of tobacco available to burn, as well as reducing the

269 contact zone responsible for heat transfer from the cigarette to the substrate. However,

270 the test system did not give reliable results largely due to variations in the composition of

271 the fabric used. Two simpler test systems were developed. The first used a simplified

272 "mock-up" test, which involved placing the smouldering cigarette on a cotton duck fabric

273 covering a block of polyurethane foam. The cigarette was deemed to cause ignition

274 when the burn line in the fabric was more than 10 mm from the side of the cigarette and

275 no ignition when the burn line was less than 10 mm. The cigarette could also be

276 classified as self-extinguishing when a portion of the tobacco rod remained unburnt. The

277 second test, the cigarette extinction test method, involved placing the smouldering

278 cigarette on a stack of 3, 10 or 15 layers of filter paper. This latter test measured the

279 propensity of the cigarette to self-extinguish.

280 In 2004, the American Society of Testing Materials (ASTM) adopted the cigarette

281 extinction test (E2187-02b; hereafter E2187) as the standard method for ignition

282 propensity due to ongoing problems with obtaining consistent samples of the test fabric

283 for the mock-up test (ASTM, 2004).

284 In 2009, Case et al. (2009) evaluated the effects of changes in the cigarette paper,

285 tobacco and circumference on cigarette ignition behaviour using the ASTM E2187

286 standard test method. They concluded that for cigarettes with either low porosity or

287 banded papers, ASTM performance was independent of cigarette circumference in the

288 range 17- 26.5 mm . The same conclusion was also reached in a later study by Coburn

289 (2010) using a parameter set that included tobacco type, stem level and circumference,

290 also in the range 17 - 26.5 mm.

291 Therefore, any influence of cigarette circumference on cigarette ignition propensity is

292 dependent on the test method used, with the current standard test method insensitive to

293 circumference changes. There are no available data on real-world fire incidence as a

294 function of cigarette circumference.

296 6. Smoke formation processes

297 The smoke formation and transport processes that occur in a burning cigarette have

298 been extensively discussed and reviewed (e.g. Egerton et al., 1963; Baker 1973; 1981;

299 1987; 1999 & 2006; DeLucia, 1978; Muramatsu, 1981; Norman, 1982; Stober, 1982;

300 Ingebrethsen, 1986; Jenkins & McRae, 1996; Muramatsu, 2005). Essentially, inside a

301 burning cigarette a large variety of chemical and physical processes are occurring

302 simultaneously in an oxygen-deficient environment, with temperatures up to 950C. The

303 physical processes occurring during combustion can be rationalized into two principal

304 mechanistic regions—termed the pyrolysis/distillation region and the combustion region

305 or zone—that exist inside the cigarette during puffing and smouldering (Figure 1).

306 The vast majority of smoke products are formed in the pyrolysis/distillation region, which

307 is immediately downstream of the heat-producing combustion zone. As the smoke

308 aerosol precursors, which consist of hot vapours and nuclei, leave this region, they cool

309 and the vapours condense around the nuclei to form the smoke aerosol. Oxides of

310 carbon are formed by both combustion and thermal decomposition of tobacco

311 constituents, as well as a significant proportion of carbon monoxide being formed by the

312 carbonaceous reduction of carbon dioxide. A proportion of the gases formed in the coal

313 diffuse out into the SS smoke, while the remainder is drawn along the tobacco rod into

314 the MS smoke. The location of these zones has been determined by mapping internal

315 gas concentrations (Adam et al., 2009; Hertz-Schunemann et al., 2015), and by

316 measuring internal density and temperature changes (Baker 1981 & 2014; Li et al.,

317 2016).

318 The quantities and chemical composition of the MS and SS smoke are influenced by the

319 chemical make-up of the tobacco filler, the physical and chemical properties of the

320 construction materials used to design the cigarette and the combined effects of the

321 tobacco, filter parameters and paper properties on the flow characteristics occurring in

322 the burning cigarette. The smoking parameters such as puff volume, duration, and

323 frequency of puffing also determine how much of each smoke component is generated

324 and distributed into the MS and SS smoke (Baker, 1999).

326 7. Smoke aerosol studies and smoke particle size

327 The particle size distribution of the smoke aerosol influences several important smoke

328 properties such as its interaction with filters and deposition in the human respiratory tract

329 (Stober, 1982; Ingebrethsen, 1986). The undiluted smoke from the burning zone of the

330 cigarette consists of a highly concentrated cloud of liquid particles with number

331 concentrations of about 1010 cm-3 and with diameters ranging from below 0.1 pm to

332 above 1.0 pm. As the smoke moves along the tobacco rod the smoke particles tend to

333 coagulate, which results in a higher average particle diameter, and a smaller number

334 concentration. The faster the particles move down the tobacco rod the less time they

335 have for coagulation and the smaller will be the average particle size. Since for a given

336 puff volume the flow rate along the tobacco rod increases with decreasing

337 circumference, it would be expected that particle sizes would be smaller at lower

338 circumference. Other factors such as particle formation, filtration, and evaporation may

339 also have an effect, but are thought to be less significant.

340 Jones and Richardson (1971) compared particle size distributions in smoke from 19 and

341 31 mm circumference cigarettes using a conifuge, as a size separating sampling device.

342 Cigarettes were smoked under standard puffing conditions which meant that flow rates

343 along the 19 mm cigarette were 2.7 times faster than along the 31 mm cigarette.

344 However there was no significant difference in mean smoke particle size (0.26 - 0.29

345 pm) between the two cigarettes calculated from the number distribution. However,

346 increasing the puff flow rate from 1.5 to 83 mL/sec (a factor of 55) decreased the mean

347 particle size by only 46%, suggesting that particle size is fairly insensitive to

"in "in i

348 circumference. The number concentrations were all in the range 1x10 to 2x10 mL

349 but the range in experimental error prevented any trends being observed.

350 Fiebelkorn & Robinson (1988) used a laser spectrometer to characterize the smoke

351 aerosols from two series of cigarettes, differing in blend type with circumferences of 13,

352 17, 20, 22, 24.75 and 29 mm. For both series of cigarettes the count median diameters

353 of the particles decreased consistently as circumference was reduced: from 0.206 pm (at

354 29 mm) to 0.143 pm (at 13 mm) for the flue-cured product and from 0.207 pm (at 29

355 mm) to 0.153 pm (at 13 mm) for the blended products. The results for the number

356 concentrations did not show a clear trend with circumference. For the flue-cured series,

357 for example, number concentrations increased from 1.56x109 mL-1 for the 29 mm

358 product to 2.82x109 mL-1 for the 22 mm product and then decreased to 1.88x109 mL-1 for

359 the 13 mm product. The apparent reduction in particle numbers at the lower

360 circumferences was ascribed, at least in part, to the inability of the spectrometer to

361 detect particles smaller than 0.1 pm, which comprised an increasing proportion of

362 particles at lower circumferences. Fiebelkorn and Robinson confirmed the importance of

363 flow rate on particle size by adjusting the puff volumes for each circumference to give a

364 common flow rate of 35.9 mL sec-1. Apart from a lower mean number concentration for

365 the 13 mm circumference cigarette, the mean particle sizes and concentrations were

366 very similar. These changes in particle sizes with circumference are consistent with the

367 higher flow rates and decreased coagulation through the slimmer cigarettes. They also

368 indicate perhaps that the laser spectrometer technique is more sensitive than the

369 conifuge in measuring particle size.

370 Egilmez compared smoke aerosol properties from four commercial US brands (Egilmez,

371 1987) with similar tar deliveries (8 mg/cig) using a laser spectrometer. Two brands had

372 circumferences of 25 mm and the other two had circumferences of 23 mm and 17 mm.

373 The ultra-slim, 17 mm product had smoke particles with count and mass median

374 diameters of 0.17 pm and 0.27 pm respectively, compared with the three other brands

375 which had similar count and mass median diameters of 0.19 pm and 0.31 pm

376 respectively. Since the brands differed in other construction parameters it was not

377 possible to attribute the smaller mean smoke particle size of the ultra-slim product to

378 circumference alone.

379 8. MS smoke yields

380 Reducing circumference affects both particulate and gas phase yields by reducing the

381 total amount of tobacco burnt; this means it will take less time for the tobacco rod to burn

382 and will result in fewer puffs. In the case of particulate smoke yields however this is

383 partially off-set by a reduction in the filtration efficiency of the tobacco rod and filter, if

384 present, due to the increased velocity of the smoke stream (Norman, 1999). For gas

385 phase components the decrease in area of the paper and the higher flow rates along the

386 rod will result in less diffusional losses. An additional factor affecting smoke yields is the

387 decrease in "dead volume" that occurs as the circumference is reduced. For example, it

388 can be calculated that the dead volume for the first puff of an 84 mm cigarette will

389 change from approximately 17% of a 35 mL puff at 30 mm circumference to

390 approximately 4% of a 35 mL puff at 15 mm circumference - this reflects the proportion

391 of smoke generated within a puff that does not leave the rod during the puff in which it is

392 generated. Smoke retained within the rod in this way can condense out onto tobacco or

393 join the SS plume escaping the cigarette.

394 8.1 MS tar, nicotine and CO yields

395 There have been a number of published and unpublished industry studies that have

396 reported yields of the tar (also termed nicotine-free dry particulate matter or NFDPM),

397 nicotine and CO from cigarettes with different circumferences (Supplementary Table 1).

398 Unfortunately many of the studies cannot be used to investigate the effect of

399 circumference alone on smoke yields. Some did not use a standard machine smoking

400 regime such as the ISO puffing parameters (2 second, 35 mL puff, once a minute)

401 (Ivinson, 1962), some only reported total particulate matter rather than tar (NFDPM)

402 (Lugton, 1971), and some used cigarette samples that did not control parameters other

403 than circumference, such as packing density (Wenusch, 1936) or filter pressure drop

404 (Reynolds & Maya, 1970). Figures 4-6 show the yields of tar, nicotine and CO from

405 three series of cigarettes (Irwin, 1989c; Izak, 1993) made with different blends, with

406 circumferences in the range 13-29 mm and the same tobacco packing densities within

407 each series. There were strong positive linear correlations between the yields and

408 circumferences. In the case of CO there were indications that at the highest

409 circumferences the yields appear to be reaching a plateau. Similar results were reported

410 by Debardeleben et al. (1978) for CO from cigarettes with circumferences in the range

411 23-26 mm. The levelling-off of the CO yields for the higher circumference cigarettes was

412 ascribed in part to increased CO diffusion.

413 Yamamoto et al. (1984) also found linear correlations between tar and nicotine yields

414 and circumference for two sets of filter cigarettes made with either a US blend or Virginia

415 tobacco, and having circumferences in the range 21.1 - 25.8 mm. They measured the

416 amounts of tar and nicotine trapped in the 20 mm filter and 10 mm tobacco butt

417 remaining after smoking, and confirmed that the amounts of trapped tar and nicotine as

418 a proportion of the total yields decreased with decreasing circumference as a result of

419 the increased smoke velocity. Both Lugton (1971) and Yamamoto et al. (1984) also

420 showed that the MS yields of tar and nicotine were directly related to the weight of

421 tobacco lost during puffing for cigarettes with circumferences from 21 - 26 mm and 19 -

422 31 mm, respectively.

423 Perfetti et al. (1983) studied puff-by-puff and total deliveries of tar and nicotine from

424 unfiltered tobacco rods with circumferences in the range of 21.5 to 24.7 mm and

425 constant packing densities. The major conclusions were that a 13% decrease in rod

426 circumference (24.7 to 21.5 mm), corresponding to a 25% reduction in rod weight,

427 resulted in a 10% decrease in puff count and reductions in yields of (FTC Federal Trade

428 Commission) tar and nicotine of 15% and 17%, respectively.

429 8.2 The nicotine/tar ratio

430 The study by Perfetti et al. (1983), referred to above, showed a small decrease (2.8%) in

431 nicotine/tar ratio as the circumference decreases from 24.7 to 21.5 mm. Robinson

432 (1987) found a 32% reduction in the nicotine/TPM ratio when circumference was

433 reduced from 29 to 13 mm. Robinson ascribed the increase in nicotine/TPM with

434 circumference to the lower flow rate in the wider rods which "enabled the aerosol to

435 absorb the nicotine more effectively". Other studies have not shown a consistent

436 relation between circumference and nicotine/tar ratios. Both Izak (1993) and Irwin

437 (1988a) found nicotine/tar ratios that increased with circumference above 20 mm but

438 also increased as circumference was reduced below 20 mm.

439 8.3 Machine smoking regime

440 Greig and Wan (2005) compared MS tar, nicotine and CO deliveries from super slim (17

441 mm) and standard (24.6 mm) circumference products when smoked under two different

442 smoking regimes: ISO - one 35 mL, 2 s puff per minute (ISO, 2012); and a modified

443 intense regime - two 55 mL, 2 s puffs per minute, vents open. There were no statistically

444 significant differences between the ratios of tar, nicotine and CO deliveries under the two

445 different smoking regimes for the super slim and standard circumference products.

446 Perfetti et al. (1983) measured tar and nicotine yields from different circumference

447 cigarettes smoked at 20, 35 and 60 mL puff volumes. Total per cigarette yields were

448 calculated from individual puff by puff deliveries, and the results showed no consistent

449 ratios between yields at different puff volumes across the circumference range 21.5-24.7

450 mm.

451 9. MS smoke toxicants

452 There have been a number of reports describing the effects of circumference changes

453 on the yields of various smoke toxicants including carbonyls (Yamazaki & Saito, 1978;

454 Irwin, 1989c; Parrish et al., 1989; Izak, 1993; Case et al., 2005; Dittrich et al., 2014),

455 phenols (Lugton, 1971; Irwin, 1988a; Irwin, 1989a; Irwin, 1989c; Dittrich et al., 2014),

456 nitric oxide (NO) (Irwin, 1988a; Irwin, 1989c; Izak, 1993; Dittrich et al., 2014), hydrogen

457 cyanide (HCN) (Irwin, 1988a & 1989c; Izak,1993; Dittrich et al., 2014), benzo[a]pyrene

458 (B[a]P) (Lugton, 1971; Dittrich et al., 2014), cadmium (Irwin, 1989c), ammonia (Parrish

459 et al., 1989; Siu et al., 2013; Dittrich et al., 2014), organic volatiles (Lugton, 1971; Irwin,

460 1989c; Randolph & Parrish, 1988; Dittrich et al., 2014) and nitrosamines (Irwin, 1988b &

461 1989b; Izak, 1993; Dittrich et al., 2014). The effects of circumference on these toxicants

462 are summarized in Supplementary Table 1. The yields of the majority of toxicants,

463 including nitrosamines, NO, phenols, B[a]P, HCN and cadmium, decrease with

464 decreasing cigarette circumference in an approximately linear fashion, although yields of

465 NO, HCN and phenols are fairly level at circumferences greater than 25 mm.

466 Carbonyl yields, particularly those of formaldehyde, show distinctly non-linear

467 relationships with circumference. The MS formaldehyde yields from experimental studies

468 covered by this review are summarised in Supplementary Table 2. Figure 7 shows

469 acetaldehyde and formaldehyde yields from 3 studies (Irwin, 1989c; Izak, 1993;

470 Yamazaki & Saito, 1978). The yields have been normalised to those at 17 mm

471 (acetaldehyde) and 25 mm (formaldehyde) circumferences to simplify comparisons

472 between studies. Acetaldehyde yields (Irwin, 1989c; Izak 1993) decreased with

473 circumference but showed a distinctly steeper decline for circumferences below 24 mm.

474 Irwin (1989c) found that formaldehyde yields increased slightly as circumferences

475 decreased from 29 to 22 mm, but then decreased as circumferences decreased from 20

476 to 13 mm. Yamazaki & Saito (1978) found no clear trend of formaldehyde yields from

477 cigarettes within the narrower circumference range of 23 to 26 mm.

478 The anomalous behaviour of the aldehydes has also been noted by Case et al. (2005)

479 who reported higher formaldehyde yields for 17 mm vs 25 mm circumference products,

480 and by Parrish et al. (1989) who observed higher formaldehyde, acetaldehyde and

481 acrolein yields at 20 mm circumference than at 17 and 25 mm. However it should be

482 noted that these latter two studies used cigarettes that differed in filter efficiencies as

483 well as circumference.

484 Dittrich et al. (2014) described a series of prototype, reduced-toxicant cigarettes which

485 included three 7 mg ISO NFDPM yield cigarettes manufactured at 17, 21 and 24.6 mm

486 circumferences but with the same tobacco blend and packing density. Changes were

487 made to the cigarette paper, filter pressure drop and ventilation levels to offset the effect

488 of tobacco weight and maintain the NFDPM specification. The cigarettes were smoked

489 under Health Canada Intense (HCI) conditions and MS yields of tar, nicotine, CO and 44

490 smoke toxicants (those mandated to be reported to Health Canada) were measured.

491 For all toxicants except pyridine, nitric oxide and formaldehyde the yields either

492 diminished as circumference decreased or the differences between yields were not

493 significant. Pyridine showed a maximum yield at 21 mm circumference while nitric

494 oxide showed a minimum yield at 21 mm. Of all the toxicants, only formaldehyde yields

495 increased monotonically as circumference decreased.

496 The involvement of free-radicals in cell transformation processes has led to the proposal

497 of various mechanisms by which free-radicals in cigarette smoke may be involved in

498 disease processes related to smoking (Church & Pryor, 1985). Free radical

499 concentrations in TPM were measured by Matkin (1988) for plain-end, US blend

500 cigarettes with circumferences of 13, 17, 20, 22, 24.75 and 29 mm. Whole smoke from

501 the 3rd puff was collected in a quartz cell and free radical concentrations were estimated

502 from the chemiluminescence of the smoke using a photomultiplier detector. Free radical

503 concentrations in the TPM decreased by approximately 28% as circumference

504 decreased from 29 to 13 mm. There was no explanation for this trend.

505 9.1 Toxicant yields per gram of tobacco

506 When expressed on a per gram of tobacco burnt basis, Izak (1993) found that yields of

507 CO, NO, HCN, water and total aldehydes increase as the circumference decreases,

508 while TSNA and nicotine yields per unit weight of tobacco have no clear relationship with

509 circumference. Irwin (1989c) similarly found that yields of aldehydes, CO, NO, HCN,

510 phenols and cadmium per unit weight of tobacco increase as circumference is

511 decreased. Figure 8 shows Irwin's data for the yields per unit weight of tobacco for

512 formaldehyde, acrolein and acetaldehyde normalised to the yield at 29 mm. Yields per

513 unit weight of tobacco increase as circumference decreases for all three aldehydes but

514 the effect is much stronger for formaldehyde than for acrolein or acetaldehyde.

515 9.2 Toxicant /tar ratios

516 Commercial cigarettes are usually designed to yield a given amount of tar (PMWNF)

517 under standard smoking conditions, so it is of interest to compare the ratios of the

518 toxicant to tar. These ratios would indicate changes in the balance of the smoke

519 chemistry which could be relevant to explaining differences, if any, in biological activity,

520 which are usually expressed as specific activities e.g. as activity per unit weight of tar.

521 Ratios of toxicant to tar from Irwin (1989c) were calculated and plotted against

522 circumference. These are shown in Figures 9 and 10. Ratios of CO, CO2, NO, HCN,

523 acetaldehyde and dimethylfuran to tar were not significantly correlated with

524 circumference, while ratios of phenols, catechol, and cadmium to tar decreased with

525 decreasing circumference (but only significantly for cadmium). In contrast, ratios of

526 acrolein and formaldehyde to tar increased significantly with decreasing circumference.

527 Similarly, for the dataset generated by Dittrich et al. (2014) all the toxicant/NFDPM ratios

528 for the 7 mg NFDPM products, except for formaldehyde/NFDPM, either decreased with

529 decreasing circumference or had maxima or minima at 21 mm. Only

530 formaldehyde/NFDPM showed a monotonic increase as the circumference decreased.

531 Irwin (1989c) pointed out that as the cigarette circumference decreased, the ratio of the

532 circumference to the cross-sectional area increased, allowing a greater proportion of the

533 tobacco to be in contact with the incoming air during a puff. Irwin hypothesized that a

534 larger proportion of oxidation reactions, including formation of formaldehyde, would be

535 facilitated as the circumference was systematically decreased.

536 To test whether more formaldehyde would be produced in a more oxidizing environment,

537 Irwin (1989c) investigated a standard circumference (25 mm) cigarette smoked in three

538 atmospheres containing 17%, 21% and 25% oxygen in nitrogen (v/v). He found that the

539 yield of tar and nicotine decreased sharply as the level of oxygen in the atmosphere

540 increased, due to much faster burning of the cigarette and a reduced puff count. The

541 ratio of formaldehyde yield to tar yield increased systematically as the level of oxygen

542 increased, supporting his hypothesis that MS formaldehyde yields are related to the

543 amount of oxidation occurring. Irwin's (1989c) results are consistent with pyrolysis

544 results of Torikai et al. (2003), who demonstrated that the addition of oxygen (or

545 oxidizers) to tobacco significantly increased the pyrolytic formation of formaldehyde

546 (Baker, 2006).

547 It could also be speculated that the finding of lower concentrations of condensate free

548 radicals at lower circumferences (Matkin, 1988) might also be related to increased

549 oxidation.

550 Although, as described above, in some studies MS formaldehyde levels have been

551 shown to be higher in smoke from slim format cigarettes, the toxicological and health

552 implications of this are unclear. Although formaldehyde is a known carcinogen, it has not

553 yet been demonstrated that, following smoking, it reaches sufficient levels in the body to

554 have pathological effects. There are very few data that demonstrate levels of

555 formaldehyde in the blood of smokers. While data published by Wang et al. (2009)

556 demonstrated measurable levels of formaldehyde adducted to DNA in the white blood

557 cells of smokers and that these were significantly higher than those seen in non-

558 smokers, in both cohorts the actual levels were in the low femtomolar range. It is difficult

559 to determine whether such low concentrations could have carcinogenic effects and

560 further, without knowledge of the smoking intensity (e.g. number of cigarettes smoked

561 per day) in the smoker group it is also difficult to gauge the significance of this finding. It

562 is also important to note that increased levels of the related cigarette smoke constituent

563 acetaldehyde have not been detected in the blood of smokers (McLaughlin et al., 1990).

564 There are differing reports about the efficiency of aldehyde uptake by smokers. Seeman

565 et al (2002) reported that acetaldehyde was not retained in the lungs and was in fact

566 mostly exhaled, whereas St. Charles et al (2013) reported almost quantitative retention

567 of formaldehyde and acetaldehyde during puffing. Seeman et al also suggested that

568 inhaled aldehydes would be quickly metabolised by aldehyde dehydrogenases in the

569 cells of the lungs (Seeman et al., 2002). Potentially, similar effects could explain the

570 extremely low levels of formaldehyde seen in the blood of smokers. Further studies are

571 required therefore to determine the actual exposure of smokers of both regular format

572 and slim cigarettes to formaldehyde in order to be able to determine any pathological

573 consequences of such exposure.

574 9.3 Toxicant yields from commercial super slim cigarettes

575 As has been stressed previously in this review, when determining the effect of

576 circumference on smoke composition it is important to ensure that other cigarette

577 parameters are kept constant. This is unlikely for commercial cigarettes which may have

578 many different specifications in addition to circumference. One approach to avoid this

579 problem is to generate an "average" smoke composition per unit weight of tar from a

580 large number of different products, and compare the test product with this average. This

581 is the essence of the "benchmark" approach used by Health Canada to estimate the

582 yields of 31 toxicants from Canadian products based on their tar deliveries (Health

583 Canada, 2000). The Canadian benchmark is generated from the toxicant yields of a

584 minimum of 28 brands obtained under both ISO and HCI smoking conditions. Siu et al.

585 (2013) compared the toxicant/tar ratios generated from the 2010 Canadian benchmark

586 with ratios measured for six super slim (17 mm circumference) brands. Since the other

587 benchmark Canadian cigarettes have circumferences of 24.5±1.0 mm this comparison

588 was expected to show the effect of reduced circumference on toxicant/tar ratios. Four of

589 the six super slim brands had flue-cured blends and two had US style blends. Two of

590 the flue-cured blends had charcoal filters and the other cigarettes had standard cellulose

591 acetate filters. Under ISO smoking conditions the toxicant/tar ratios for all six super slim

592 products were either significantly lower than the benchmark, including acetaldehyde (4/6

593 brands), butyraldehyde (4/6 brands) and propionaldehyde (4/6 brands), or were not

594 significantly different from the benchmark, including formaldehyde (6/6 brands). Under

595 HCI smoking the super slim brands had significantly greater yields of ammonia (6/6),

596 nicotine (4/6) and formaldehyde (4/6). In addition the two US blended products had

597 higher yields of the tobacco specific nitrosamines (NNN, NAT and NAB) and 4598 aminobiphenyl and 2-aminonaphthalene. All the other toxicants were either significantly

599 lower than, or not significantly different to, the bench mark. Toxicant yields from one of

600 the super slim brands were also compared to those from a single market brand with the

601 same length, filter type and blend type but with a circumference of 25 mm. In contrast to

602 the bench mark comparison, the super slim cigarette gave higher yields of

603 formaldehyde, pyridine, acetamide and phenol per unit tar than the 25 mm

604 circumference cigarette under ISO smoking conditions, but equal or lower toxicant ratios

605 for all toxicants under HCI smoking conditions.

606 10. SS smoke chemistry

607 SS yields of tar, nicotine, CO and CO2 decrease with decreasing circumference (Perfetti

608 et al., 1983; Chao, 1985; Case et al., 1987; Izak, 1993). These reductions are strongly

609 correlated with the weights of the tobacco in the cigarette rod, which, at constant packing

610 density, are also proportional to the square of the circumference. The data of Perfetti et

611 al. (1983) from cigarettes with circumferences of 21.5-24.7 mm, and Chao (1985) from

612 cigarettes with circumferences of 13-22 mm show strong linear correlations between the

613 square of the circumference and SS tar and SS nicotine.

614 Table 1 shows the relationship between the smoke yields of tar, nicotine CO and CO2 in

615 MS smoke (MS) and SS for non-filtered cigarettes of constant packing density across a

616 range of circumferences using data from Perfetti et al. (1983). All MS and SS yields

617 decrease with decreasing circumference, but the ratios of SS/MS yields decrease only

618 very slightly with decreasing cigarette circumference.

619 There have been several studies of smoke toxicants in SS. Izak (1993) reported TSNA

620 yields per unit weight of tobacco for cigarettes with circumferences in the range 17-27

621 mm. For NAT and NNN, SS yields per g tobacco were independent of circumference.

622 For NNK, yields per g tobacco peaked at 24 mm circumference and were lower at other

623 circumferences.

624 Parrish et al. (1989) measured SS yields of benzene, toluene and the volatile aldehydes

625 for two sets of cigarettes made at 17, 20 and 24.8 mm circumference. One set was

626 made with conventional cigarette paper and the other with a low SS paper containing

627 magnesium hydroxide (Mg(OH)2) filler. Benzene and toluene SS yields decreased

628 linearly with the weight of tobacco in the cigarette (and with the square of

629 circumference). However formaldehyde, acetaldehyde, acrolein and butyraldehyde all

630 gave distinctly non-linear correlations with tobacco weight. Plots of acetaldehyde,

631 formaldehyde and acrolein are shown in Figure 11. The reason for the non-linearity is

632 unknown, but Irwin's hypothesis (Irwin 1989c) of increased smoke oxidation at low

633 circumferences would be consistent with these results.

634 Dittrich et al. (2014) described a series of prototype cigarettes which demonstrated a

635 number of different approaches for reducing toxicant yields. Included in this study were

636 three 1 mg ISO NFDPM yield cigarettes manufactured at 17, 21 and 24.6mm

637 circumferences but with the same tobacco blend, packing density, paper type and filter

638 tow. These were smoked under ISO smoking conditions and the SS yields of 44 smoke

639 toxicants (those mandated to be reported to Health Canada) were measured. The SS

640 yields of all the toxicants, except for formaldehyde, decreased with decreasing

641 circumference. Formaldehyde yields increased as circumference decreased from 24.6

642 to 21 mm before decreasing to their lowest level at 17mm circumference.

643 11. Biological activity

644 Whole smoke and/or condensate from cigarettes with different circumferences have

645 been subjected to a number of different tests for bioactivity. These have included in vitro

646 mutagenic and clastogenic testing of the condensate (Izac, 1993; Irwin, 1989c; Massey

647 & Barnes, 1987; Massey & Godden, 1987; Massey, 1989 & 1991; Mladjenovic et al.,

648 2013; Coggins et al., 2013), testing for acute toxicity of whole smoke and condensate

649 using micro-organisms (Lugton, 1971; Coggins et al., 2013), in vivo tumorigenicity

650 testing of condensate using mouse skin painting (Lugton, 1971; Clapp et al., 1977;

651 Dontenwill et al., 1977; Smith, 1990) and whole smoke using inhalation toxicology

652 (Smith, 1990).

653 11.1 In vitro mutagenicity and clastogenicity tests

654 There have been several reports of the effect of circumference change on the Ames test

655 which determines the mutagenicity of condensate to different strains of Salmonella

656 Typhimurium bacteria (Massey & Godden, 1987; Irwin, 1989c; Massey, 1989; Izac,

657 1993; Mladjenovic et al., 2013; Coggins, 2013). The bacteria are exposed to various

658 dilutions of smoke condensate, which is collected either on a Cambridge filter or in an

659 impaction trap.

660 The activity of the condensate is usually reported on a per unit weight of condensate

661 basis and is then referred to as "specific activity". However, in some cases, activities are

662 reported on a unit tar (NFDPM) basis. Both of these normalisation approaches decouple

663 the impact of different quantities of smoke in the assays, allowing any influence of

664 circumference to be clearly observed.

665 Studies have consistently shown reductions in specific activity with reducing

666 circumference using both TA98 and TA100 strains of bacteria (Izak, 1993; Coggins,

667 2013). For example, Massey (1989) determined specific Ames activities (strain TA98

668 with S9 activation) of condensates from flue-cured and US-style cigarettes with

669 circumferences of 13, 17, 20, 22, 24.75 and 29 mm. Specific mutagenic activities fell by

670 49% and 39% for the flue-cured and US blended series, respectively, when the

671 circumference was reduced from 29 to 13 mm. Part of the reason for the reduced

672 activity may be due to the higher flow rates through the cigarette, which result in less

673 effective filtration of the more volatile, and less mutagenic, smoke components by the

674 tobacco rod and filter (Robinson, 1987). Massey (1989) tested the magnitude of this

675 effect by modifying the puff volume drawn through the cigarettes in order to produce

676 equal linear air flow at all circumferences. This resulted in the cigarettes with

677 circumferences of 22-29 mm having specific activities that were not significantly

678 different. However the lowest circumference cigarettes (13 and 17 mm) still had

679 significantly lower specific activities than those with higher circumference. Massey

680 speculated that at very low circumferences the higher ratios of circumference to cross-

681 sectional area may provide more oxygen during puffing as suggested by Irwin (1989c) to

682 explain the relatively higher formaldehyde/tar ratios for lower circumference cigarettes.

683 This is supported by findings that increased oxygen in the combustion zone results in

684 condensate with reduced Ames activity (Massey, 1989).

685 Mladjenovic et al. (2013) compared the Ames mutagenicities of 11 Canadian cigarette

686 brands using Salmonella strains TA98, YG1041 and YG5185. The cigarettes had

687 different blends, filter types, ventilation levels and circumferences. Five brands were

688 super slim with circumferences of 16.8 ±0.2 mm and 6 brands had circumferences of

689 24.5 ±1.0 mm. After taking into account the differences in blend types it was concluded

690 that the super slim brands had significant lower mutagenicities than the 24.5 mm

691 products.

692 The influence of circumference on the clastogenic activity of smoke condensate (i.e. the

693 number of chromosome aberrations per mg of condensate) in human lymphocytes has

694 also been investigated (Massey, 1991). The specific activity of a flue-cured 13-mm

695 cigarette condensate was less than that of a 24.75 mm cigarette condensate of the

696 same blend composition.

697 11.2 In vitro cytotoxicity tests

698 The effect of circumference on the acute toxicity of smoke was investigated using a

699 number of short term tests involving microorganisms applied to smoke from cigarettes

700 with circumferences of 19, 22, 25, 28 and 31 mm (Lugton, 1971). The paramecium

701 hanging-drop test measures vapour phase toxicity and involves passing successive

702 puffs of smoke past a water droplet containing the ciliate (BAT, 1969a). The number of

703 puffs required to kill the ciliate is recorded. In this test, no significant difference was

704 observed between cigarettes of different circumference implying no difference between

705 toxicities of each puff.

706 The Tetrahymena solution test measures the cytotoxicity per cigarette of various

707 dilutions of whole smoke in aqueous solutions of tetrahymena vorax (BAT, 1969b). The

708 lowest circumference cigarettes had smoke with lower cytotoxicities in line with the TPM

709 yields. The Tetrahymena particulate-phase test measures the specific cytotoxicity of the

710 tar (BAT, 1970). It involves treating Petri dishes containing Tetrahymena vorax with

711 different concentrations of tar in acetone. The compounds responsible for this

712 cytotoxicity are thought to be chemically different from those that kill the microorganism

713 when whole smoke is employed. Tar from the lowest circumference cigarettes showed a

714 significantly lower specific activity than from the highest circumference cigarettes.

715 The chorioallantoic membrane test was used to examine the toxicity of smoke

716 condensate by measuring the thickness of the chorioallantoic membrane of fertile hens'

717 eggs after smoke condensate had been applied for 4 days (BAT, 1969c). There were no

718 significant differences in specific activity between smoke condensates from different

719 circumference cigarettes. However, on a per cigarette basis, the smoke condensate from

720 cigarettes of smaller circumference were significantly less active than from the larger

721 products, which reflects the lower weights of condensate from these cigarettes.

722 More recently, Coggins (Coggins, 2013) reported the results of the neutral red uptake

723 assay on the condensates from cigarettes with circumferences of 17, 21 and 23.9 mm.

724 Relative to the 27.1 mm circumference (control) cigarette, the specific toxicities (1/EC50)

725 on a per weight of smoke condensate basis decreased from 1.22 for the 23.9 mm

726 cigarette, to 0.99 for the 21 mm cigarette and to 0.83 for the 17 mm cigarette.

727 In general, data from Ames tests and from other in vitro toxicological tests indicate that

728 as the circumference of a cigarette decreases (yielding lower cigarette smoke

729 condensate deliveries), the toxicological activity of the smoke decreases above and

730 beyond the amount of smoke generated by these cigarettes.

731 11.3 In vivo tests

732 A few studies have assessed the effect of circumference on the tumorigenicity of smoke

733 using mouse skin painting (Clapp et al., 1977; Dontenwill et al., 1977; Smith, 1990).

734 In a study by the Tobacco Research Council (Smith; 1990), a decrease in tumour-

735 forming specific activity was found for smoke condensate from cigarettes of 19 mm

736 circumference as compared with condensate from products of 25.3 mm and 31.5 mm

737 circumference. There was no difference between the condensates from the 25.3 and

739 Clapp et al. (1977) found that the specific activities of condensates from 23 mm

740 cigarettes were less active than those from 25.4 mm cigarettes. This was found for both

741 100% tobacco cigarettes and for blends with tobacco substitute (NSM).

742 Dontenwill et al. (1977) compared tumorigenicities of condensates from cigarettes with

743 circumferences of 21.7 mm, 25.5 mm and 28.9 mm. Condensate from the 21.7 mm

744 cigarette was significantly lower in specific activity than that from the 25.5 mm cigarette.

745 Condensates from the 25.5 mm and 28.9 mm product were not significantly different.

746 11.4 Inhalation toxicity

747 Smith (1991) reported inhalation toxicological testing of cigarette smoke from cigarettes

748 with circumferences of 13, 17, 20, 25 and 29 mm circumference. The 6-week inhalation

749 study on rats involved exposing the animals to 7.9-8.6 mg/L of TPM on a twice daily

750 basis. There were no consistent differences in response between the treatment groups.

751 Overall, it seems clear that as cigarette circumference decreases, the specific

752 tumorigenic activity of cigarette smoke also decreases. However the specific toxicity of

753 the smoke during inhalation is not affected by circumference.

754 12. Mouth level exposure studies

755 As described above, many studies have documented lower MS smoke yields of a wide

756 range of chemicals in cigarette smoke from slim format cigarettes. However, this does

757 not necessarily mean that smoking these cigarettes reduces either the human exposure

758 to these chemicals or modifies the risks associated with smoking. Although a person's

759 mouth level exposure to smoke can be determined from puff duplicators, analysis of

760 discarded butts after human smoking is a much less invasive and more rapid technique.

761 A more recent improvement in butt analysis is the part filter analysis method in which

762 only the mouth-end portion of the filter, downstream of the ventilation holes, is used for

763 analysis (BAT, 2016). In this portion, the filtration efficiency is relatively constant

764 irrespective of typical puff flow rates of humans and also minimizes butt length effects

765 (e.g. nicotine condensation) on filtration efficiency. Therefore, the estimations of human

766 smoking cigarette yields are better correlated to human smoking conditions than

767 previous whole-filter methods (St. Charles et al., 2009).

768 In the first of two studies of slim cigarettes performed using this technique, Ashley et al.

769 (2011) examined mouth level exposure (MLE) to tar and nicotine in cohorts of Romanian

770 smokers of king size cigarettes with circumferences of either 25 mm (conventional) or 17

771 mm (super slims). No significant differences were found between the MLE to 'tar' and

772 nicotine in smokers of the conventional and slim cigarette over a range of different ISO

773 tar yields (1 mg, 4 mg and 7 mg ISO tar per cigarette). This suggested that cigarette

774 circumference had no influence on smokers' exposure to tar or nicotine. In a second and

775 similar follow-up study performed in Russia (Ashley et al., 2014), MLE to tar was found

776 to be similar for smokers of 1 mg ISO tar yield products, but lower for smokers of 4 mg

777 and 7 mg super slim cigarettes, compared to conventional format cigarettes. MLE to

778 nicotine was lower in smokers of 4 mg super slim compared to conventional cigarettes,

779 but not for other tar bands. The results for both the Romanian and Russian studies are

780 summarised in Table 2. These studies demonstrate that smokers' exposure to tar and

781 nicotine are either similar or lower in smokers of slim format cigarettes when compared

782 to those seen in smokers of conventional cigarettes. It must be noted however that this

783 does not imply any difference in disease risk associated with smoking different styles of

784 cigarette and further studies would be required in order to evaluate such differences in

785 risk, if any.

787 Conclusions

788 This review of academic and industry-based studies has shown that decreasing cigarette

789 circumference influences the physical properties of the cigarette and, as a result, the

790 nature of the smoke produced. Tobacco weight, mass burn rate, puff count and static

791 burn time decrease with decreasing circumference, while draw resistance and the length

792 of rod burned during puff and smoulder periods increase. In addition, the average smoke

793 particle size decreases with cigarette circumference due to the faster flow rate along the

794 cigarette and shorter time available for particle coagulation. Overall, deliveries of

795 individual MS and SS smoke constituents, including free radical species, tend to

796 decrease as circumference is reduced, except for formaldehyde, which, in some cases,

797 increases relative to tar as circumference decreases. In terms of bioactivity, in vitro

798 specific mutagenic, cytotoxic and tumorigenic activities decrease as circumference

799 decreases in the range 29 to 13 mm. The specific toxicities of the smoke to the rodent

800 respiratory tract are not sensitive to circumference changes. The increases in

801 formaldehyde relative to tar and the reduction in some of the specific bioactivities of the

802 condensate with decreasing circumference appear to be related at least in part to a more

803 oxidising burning zone. Recent studies on MLE to smoke amongst smokers of slim and

804 conventional circumference products found that exposure to tar and nicotine was either

805 lower in smokers of 17 mm circumference cigarettes compared with smokers of

806 conventional 25 mm circumference cigarettes or not significantly different. It must be

807 emphasized that although reduced circumference is a cigarette design feature that can

808 be used in conjunction with other parameters to help reduce certain MS and SS smoke

809 toxicants and some measures of bioactivity, there is no evidence that slim cigarettes per

810 se are any less harmful than cigarettes with higher circumferences.

811 812

814 BAT - British American Tobacco

815 M LE - Mouth level exposure

816 HCI - Health Canada Intense smoking regime

817 MS - Mainstream (smoke)

818 NFDPM - Nicotine-free, dry particulate matter

819 SS - Sidestream (smoke)

820 TPM - Total particulate matter

822 Declaration of interest

823 K. McAdam, A. Eldridge, I.M. Fearon, C. Liu, A. Manson, J. Murphy and C. Proctor are

824 employees of British American Tobacco (Investments) Ltd. A. Porter is a paid consultant

825 for British American Tobacco (Investments) Ltd. Preparation of the manuscript was

826 funded by British American Tobacco (Investments) Ltd.

828 Figure captions

829 Figure 1. The burning cigarette during smouldering and puffing (after Baker, 1981)

830 Figure 2. Linear (LBR) and mass (MBR) burn rates vs circumference during free

831 smoulder of 70 mm untipped cigarettes. Data from Lugton, 1971.

832 Figure 3. Puff number vs tobacco weight (from Baker, 1973). A is a US blend 84 mm

833 filter cigarette, B & C are plain-end, flue-cured blend 72 mm cigarettes, and D is a 70

834 mm plain-end, flue-cured lamina cigarette.

835 Figure 4. Tar vs circumference with linear regressions for three series of cigarettes. The

836 data used from Irwin, 1989c are for NFDPM measured using flue-cured (FC) and US

837 blend (US) cigarettes. The data from Izak, 1993 are for FTC tar measured using US

838 blend cigarettes.

839 Figure 5. Nicotine vs circumference with linear regressions for three series of cigarettes.

840 The data from Irwin, 1988a are for flue-cured (FC) and US blend (US) cigarettes. The

841 data from Izak, 1993 are for US blend cigarettes.

842 Figure 6. CO vs circumference with quadratic regressions for three series of cigarettes.

843 The data from Irwin, 1988a are for flue-cured (FC) and US blend (US) cigarettes. The

844 data from Izak, 1993 are for US blend cigarettes.

845 Figure 7. Relative yields of acetaldehyde and formaldehyde vs circumference using

846 data from Irwin, 1989c; Izak, 1993 and Yamazaki & Saito, 1978. Yields are normalised

847 to 17 mm circumference (acetaldehyde) and to 25 mm (formaldehyde).

848 Figure 8. Aldehyde yields per unit weight of tobacco burnt vs circumference. Yields are

849 normalised to those at 29 mm circumference. Data from Irwin, 1989c.

850 Figure 9. Ratios of CO, CO2, HCN, phenols and Cd to NFDPM vs circumference. Data

851 from Irwin, 1988a & 1989c.

852 Figure 10. Ratios of aldehydes, dimethylfuran and catechol to NFDPM vs circumference.

853 Data from Irwin, 1988a & 1989c.

854 Figure 11. SS yields of formaldehyde, acetaldehyde and acrolein vs tobacco weight.

855 Data from Parrish et al., 1989. "Control" cigarettes have conventional paper. "Test"

856 cigarettes have low-SS Mg(OH)2 papers.

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1200 1201

Table 1. Yields and ratios of sidestream (SS) and mainstream (MS) tar, nicotine, CO and CO2 for non-filtered cigarettes with constant packing density. Data from Perfetti et al., 1983.

Circumference (mm) a

21.5 22.8 23.7 24.7

Tar (mg/cig) 24.1 25.7 26.2 28.3

Nicotine (mg/cig) 1.53 1.66 1.78 1.85

CO (mg/cig) 13.5 15.4 15.3 16.1

CO2 (mg/cig) 36.2 38.5 38.7 40.8

Puff Number_7.5_7.7_8.0_83

Tar (mg/cig) 18.8 20.4 22.5 25.4

Nicotine (mg/cig) 2.96 3.37 3.78 4.33

CO (mg/cig) 36.9 38.5 44 47.5

CO2 (mg/cig)_309_337_389_420_

SS/MS ratios

Tar 0.78 0.79 0.86 0.90

Nicotine 1.93 2.03 2.12 2.34

CO 1.02 1.00 1.14 1.16

CO2 22.9 21.9 25.5 26.1

All cigarettes had a packing density of 0.287 g cm-3. MS yields were measured under standard FTC conditions. SS yields were measured by the so-called "fishtail chimney" method (Coresta, 2011).

Table 2. Mouth level exposures (MLE) to tar and nicotine for cigarettes with 24.6 and 17 mm circumferences. Data from Ashley et al., 2011 & 2014.

Study ISO NFDPM (mg/cig) Circumference (mm) MLE to tar (mg/cig) MLE to nicotine (mg/cig)

1 17.0 7.1 ±2.1c 0.70±0.19c

4 24.6 11.9±2.9b 1.04±0.28b

Romania 4 17.0 10.5±2.2b 1.00±0.20b

7 24.6 16.3±4.2a 1.40±0.33a

7 17.0 15.2±3.7a 1.36±0.33a

1 24.6 8.9±3.4d 0.98±0.35cd

1 17.0 9.4±3.2d 0.86±0.28d

Russia 4 4 24.6 17.0 16.7±5.1b 13.5±4.2c 1.53±0.48a 1.18±0.35bc

7 24.6 19.5±6.2a 1.43±0.50a

7 17.0 16.8±4.9b 1.33±0.38ab

All cigarettes were 83±4mm in length and had carbon filters.

Values with same alphabetical character are not significantly different (P<0.05)

a. G moulder


Successive coal shapes over a 15 second period

b, Puffing

Lighit gases diffusing out i

Sidestream i smoke

i Sidestream

A CombuDlior zone B Pyrolysis and distillation zone




Circumference (mm)

22.5 -| 20.0 17.5 H

* 15.0 H

^ 12.5H £

° 10.°H

7.5 5.0H

• ^^ —•

> ''''

/ ■ / X


Irwin, 1988a (FC) Irwin, 1988a (US) Izak, 1993

15 20 25

Circumference (mm)


{/) T3

aj V e

? 1.25-


i— Acetaldehyde (Irwin)

— Acetaldehyde (Izak)

' - Formaldehyde (Irwin)

— Formaldehyde (Yamazaki)

Circumference (mm)

• acetaldehyde

■ acrolein


—A - formaldehyde

— catechol

• SS Formaldehyde Control

■ SS Formaldehyde Test

—♦-- SS Acetaldehyde Control

- SS Acetaldehyde Test

—►-- SS Acrolein Control

SS Acrolein Test


• Reducing cigarette circumference reduces puff count and increases draw resistance.

• Nicotine and most smoke toxicant yields decrease with decreasing circumference.

• Ratios of mainstream formaldehyde to tar increase as circumference decreases.

• Specific smoke condensate biological activity reduces as circumference decreases.

• Among smokers mouth-level exposures are not significantly affected by circumference.