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Regulatory Toxicology and Pharmacology 82 (2016) 111e126

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Regulatory Toxicology and Pharmacology


journal homepage: www.elsevier.com/locate/yrtph

Influence of cigarette circumference on smoke chemistry, biological


activity, and smoking behaviour
Kevin McAdam a, *, Alison Eldridge a, Ian M. Fearon a, Chuan Liu a, Andrew Manson a,
James Murphy a, Andrew Porter b
a
Group Research & Development, British American Tobacco (BAT), Regents Park Road, Southampton, SO15 8TL, UK
b
3810 Saint Antoine West, Montreal, QC, Canada

a r t i c l e i n f o a b s t r a c t

Article history: Cigarettes with reduced circumference are increasingly popular in some countries, hence it is important
Received 28 July 2016 to understand the effects of circumference reduction on their burning behaviour, smoke chemistry and
Received in revised form bioactivity. Reducing circumference reduces tobacco mass burn rate, puff count and static burn time, and
8 September 2016
increases draw resistance and rod length burned during puff and smoulder periods. Smoulder temper-
Accepted 11 September 2016
Available online 12 September 2016
ature 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
Keywords:
Cigarette
smoke toxicants. However, volatile aldehydes, particularly formaldehyde, show a distinctly non-linear
Circumference relationship with circumference and increases in the ratios of aldehydes to tar and nicotine have been
Smoulder observed as the circumference decreases. Mutagenic, cytotoxic and tumorigenic specific activities of
Smoke yields smoke condensates (i.e. per unit weight of condensate) decrease as circumference decreases. Recent
Bioactivity studies suggest that there is no statistical difference in mouth-level exposure to tar and nicotine among
Formaldehyde smokers of cigarettes with different circumferences. Commercially available slim cigarettes usually have
Slim 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.
Crown Copyright © 2016 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction composition of the smoke which can affect its specific biological
activity, which is the activity per unit weight of the smoke or one of
Although cigarette rods are generally cylindrical in shape they its components such as nicotine. Understanding these relationships
can, and have, been made in a variety of lengths and circumfer- is important both when interpreting chemical and biological assays
ences. Reasons for adopting different dimensions include cost, associated with circumference changes and in understanding
marketing objectives and government regulations. However smoker behaviour or smoker perception studies.
changing the cigarette dimensions may affect the smoke formation Although experimental cigarettes have been made with cir-
and transport processes within the cigarette rod which in turn cumferences ranging from as low as 10 mm up to 70 mm (Perfetti
could affect the yields of both mainstream (MS) and sidestream (SS) and Norman, 1986; Luke, 1986; Norman et al., 1988; Lewis, 1989;
smoke (Norman, 1999). There are also potential changes to the White and Perfetti, 1992), the dimensions of commercial products
are limited by cigarette manufacturing machine constraints, prod-
uct performance standards and consumer acceptability. Traditional
king size cigarettes have circumferences of 24e25 mm, while
Glossary and abbreviations: BAT, British American Tobacco; MLE, Mouth level slimmer styles of cigarette can have circumferences that range from
exposure; HCI, Health Canada Intense smoking regime; MS, Mainstream (smoke);
14 to 24 mm. While the nomenclature is not standardised, ciga-
NFDPM, Nicotine-free dry particulate matter; SS, Sidestream (smoke); TPM, Total
particulate matter. rettes with circumferences between 22 and 24 mm are often
* Corresponding author. termed “slim”, those between 19 and 22 mm are referred to as
E-mail address: Kevin_McAdam@bat.com (K. McAdam).

http://dx.doi.org/10.1016/j.yrtph.2016.09.010
0273-2300/Crown Copyright © 2016 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
4.0/).
112 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

demi-slims and those in the range 14e19 mm are termed “super example, smoke chemistry or bioactivity. However some studies of
slim”. There are also a few “wide” cigarettes on the market with smoke toxicants from commercial low circumference cigarettes are
circumferences of 27e28 mm, which are considerably larger than also reviewed in section 9.3.
traditional king size cigarettes. Cigarettes of different circumfer- Historically, the effects of cigarette rod circumference have been
ence can be made with or without filters and are generally found well studied (e.g. Arany-Fuzessery et al., 1982; Gugan, 1966;
commercially in lengths of 80e85 mm, 90e100 mm and 120 mm. Muramatsu, 1981; 2005; Resnik et al., 1977; Yamamoto, 1981)
Reduced circumference cigarettes have been marketed for well with the first investigations, which focused on nicotine yields,
over sixty years. Early examples include the plain end and filter dating back to 1936 (Wenusch, 1936). Further research coincided
versions of the Homa cigarette brand which were first produced by with the commercialisation of lower circumference cigarettes in
the Iranian Tobacco Company in the early 1950s and 1960s, the 1950s, and with the introduction of the Cigarette Safety Act in
respectively, and had circumferences of 19.75 mm (Reemstma, the mid-1980s when cigarette circumference was one of the vari-
1987). In 1973 Lugton (1973) described a large number of com- ables studied in attempts to understand ignition propensity of
mercial brands from around the world including Players No 6 Filter, cigarettes. A new phase, currently ongoing, involves analysing
marketed as a lower cost alternative brand in the UK with a total market trends towards slimmer cigarettes, as well as research into
length of 66 mm and a circumference of 23.2 mm, as well as plain- reduced toxicant prototype cigarettes (Dittrich et al., 2014). In
end cigarettes from Kenya with even lower circumferences: reference to the latter aspect, reducing circumference has been one
21.9 mm for King Stork, 20.8 mm for Crescent and Star and 18.1 mm of a number of cigarette design parameters that have been inves-
for Ten Cents. Samfield (1991) described an Egyptian brand, King tigated as a potential route towards harm reduction (Branton et al.,
George V from the mid-1950s, with a circumference of 17.4 mm. 2011a; Branton et al., 2011b; Liu et al., 2011; McAdam et al., 2011;
In the US, Virginia Slims with a circumference of 23 mm and a McAdam et al., 2012).
length of 100 mm were introduced in 1968, and the first brand
marketed as a “super slim”, Capri, was launched in 1987 and had a
circumference of 17 mm.
Currently, reduced circumference cigarette products are 2. Physical properties of the cigarette
becoming more popular in certain areas of the world. Markets with
the highest share of slim products are South Korea, Indonesia, Circumference is one of several variables that can be altered
Kazakhstan and Iran where they are predominantly smoked by during cigarette design and, as will be seen in this review, it has an
adult males (Park, 2009). In the European Union, research by the impact on cigarette physical properties as well as smoke chemistry
European Commission has shown that the market share of reduced and bioactivity.
circumference cigarettes grew significantly within a declining EU There are two major physical changes that occur when cigarette
cigarette market from ~3.6% in 2006 to ~6% in 2012 (EC, 2013). This circumference is reduced. The first, perhaps self-evident, is that at a
is consistent with global trends where sales of reduced circumfer- constant packing density (the density of tobacco in the cigarette
ence cigarettes have been reported to have grown ten times faster rod) and tobacco rod length, the tobacco weight is reduced in
than the overall market in the past five years (EC, 2013). The lack of proportion to the volume reduction, or cross-sectional area. The
association between smoking prevalence rates and market share of second is that resistance to draw, or pressure drop, increases in
slim (<7.5 mm diameter, <23.6 mm circumference) cigarettes has inverse proportion to the reduced cross-sectional area at a constant
been confirmed by studies of smoking data in up to 96 countries for volumetric flow. In mathematical terms the pressure drop along a
the years 1996, 2006 and 2012 (Slater, 2016). After accounting for tobacco rod can be described (Schneider and Schluter, 1987) by a
socio-economic and cultural confounding factors, the correlation modified Kozeny-Carman equation (Carman, 1956). The Kozeny-
between smoking prevalence and market share of slim cigarettes Carman equation is used in the field of fluid dynamics to calcu-
for males was only significant (at P < 0.1) for one of the years (2012), late the pressure drop of a fluid flowing through a packed bed of
and, for females, there were no significant correlations for any of solids under lamina flow. For a tobacco rod the equation can be
the years. written as:
Given the increasing interest in slim circumference cigarettes, h . i
this review examines the effects of changing cigarette circumfer- PD ¼ K ðrP =rT Þ2 ð1  rP =rT Þ3 F=A
ence on cigarette physical properties, burn rates, combustion h . i .
temperatures, MS and SS smoke chemistry, smoke toxicity and ¼ K ðrP =rT Þ2 ð1  rP =rT Þ3 F4p C 2
smoking behaviour. In this review we have made use of both peer-
reviewed papers published in the open literature as well as un- Where K is an empirical factor related to the tobacco particle shape
published tobacco industry documents, sourced from the Legacy and tortuosity of the spaces between the particles, F is the flow rate
Documents database. Also note that all the unpublished industry of air drawn through the rod, A is the cross-sectional area of the
documents (except a reference to Mouth Level Exposures on the cigarette, C is the circumference, rP is the packing density and rT is
BAT website) can be easily identified since they include a link to the the density of the tobacco shreds.
Legacy website and the link is always preceded by “industry doc- The equation shows that pressure drop is inversely proportional
uments” or “legacy”. to the cross sectional area, or square of circumference, and it is also
The review focuses mainly on the effects of circumference very sensitive to the packing density of the blend, rP. Several au-
change alone, so that the influence of confounding design variables thors (Norman, 1999; Hook, 1985) have pointed out that many of
can be avoided. These data are mostly available from experimental the early studies of the effects of circumference change either failed
studies performed by tobacco industry laboratories in which series to adequately control packing density (e.g. Wenusch, 1936), or
of cigarettes with only changes in circumference were designed and deliberately altered packing density to obtain a constant pressure
tested. However commercial, low circumference cigarettes are drop. Since pressure drop affects ventilation into the smoke stream
designed to be acceptable to smokers and other design features through the paper or filter as well as the filtration of smoke par-
such as levels of filter ventilation, tobacco packing density or paper ticulate along the rod (Norman, 1999) some of the early studies
porosity may also change. It is beyond the scope of this review to relating cigarette circumference to other cigarette physical prop-
assess the interaction of other variables with circumference on, for erties and smoke yields may not be reliable.
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 113

3. Burn rate and puff number increases rapidly, from about 600  C to greater than 900  C, which
causes the impedance to gas flow within the coal to increase. As the
The smouldering and puffing processes in a burning cigarette puff proceeds, air tends to preferentially enter the burning zone of
have been studied extensively and have been comprehensively the cigarette behind the paper burn line where the draw resistance
reviewed (Baker, 1981; 1999). During free smoulder, cigarette is lowest (Baker, 1999). The exothermic combustion of tobacco in
combustion is maintained by diffusion of oxygen through the this region causes the periphery of the tobacco rod to burn down
charred burn-line zone of the cigarette paper into the back of the more rapidly than the central zone, resulting in an elongated coal
burning coal as shown in Fig. 1a. As the circumference is reduced section. At the end of the puff, the periphery cools quickly and the
and the tobacco weight per unit rod length decreases, the smoulder paper burn line stops advancing. At the same time the center of the
rate is affected: the rate at which the length of tobacco rod is coal advances more rapidly until the coal resumes its initial shape.
consumed (“linear burn rate”) increases while the rate at which The time between the end of the puff and the re-establishment of
tobacco is consumed (“mass burn rate”) is reduced (Ivinson, 1962; the coal shape may take 15e20 s (Li et al., 2016).
Rice, 1968; Rice et al., 1970; Lugton, 1971; Resnik et al., 1977; There have been several studies of burn rates during puffing
Muramatsu, 1981; Perfetti et al., 1983; Arany-Fuzessery et al., (Egerton et al., 1963; Resnik et al., 1977; Yamamoto, 1981;
1982). This is illustrated in Fig. 2 which shows the linear and mass Muramatsu, 1981; Perfetti et al., 1983). All the studies showed
burn rates for tobacco rods with circumferences ranging from 19 to that under puffing conditions decreasing the circumference of the
31 mm (Lugton, 1971). Over this range of circumferences the linear cigarette at constant tobacco density decreases the volume (and
burn rate is inversely proportional to the circumference while the therefore mass) of tobacco consumed during the puff and during
mass burn rate is directly proportional to the circumference. the inter-puff smoulder period. Yamamoto (1981) for example
Yi et al. (2001) developed a semi-empirical mathematical model measured weight losses during puffing for a series of unfiltered
to describe free-smouldering behaviour of cigarettes. Their results tobacco rods with circumferences in the range 20.5e27.0 mm. As
for mass and linear burn rates were in good agreement with the circumference decreased the weight losses also decreased.
experimental values obtained by Rice et al. (1970) and Resnik et al. Muramatsu (1981) measured the linear burn rates during smoking
(1977). Their model also showed that mass burn rate was more of unfiltered tobacco rods with constant packing density and cir-
sensitive to changes in circumference than changes in packing cumferences ranging from 20.3 to 26.1 mm. Linear burn rates
density, as also found experimentally. during puffing were about 20 times faster than during free
During puffing, air is drawn along the tobacco rod and through smoulder, while between puffs the smoulder rates were about 20%
the coal (Fig. 1b). At the start of the puff the coal temperature slower on average than with a cigarette smouldering in a non-

Fig. 1. The burning cigarette during smouldering and puffing (after Baker, 1981).
114 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

LBR (mm/min) MBR (mg/min)


75
5.0
70

4.5 65

60

4.0
55

50
3.5
45

3.0 40
20.0 22.5 25.0 27.5 30.0 20.0 22.5 25.0 27.5 30.0
Circumference (mm)

Fig. 2. Linear (LBR) and mass (MBR) burn rates vs circumference during free smoulder of 70 mm untipped cigarettes. Data from Lugton, 1971.

puffed experiment. The length burned during puffing (2 s puffs) Yamamoto et al. (1984) showed that over a limited range of cir-
was, on average, about 18% greater than that between puffs (58s cumferences (21e26 mm) the puff number was directly propor-
intervals). tional to the circumference. However in this relatively narrow
Perfetti et al. (1983) measured burn rates during the puff and range of circumference Yamamoto's data also correlates equally
during the inter-puff smoulder period. Unfiltered tobacco rods, well with the square of circumference.
with circumferences of 21.5e24.7 mm, were each smoked at three
puff volumes (20, 35, and 65 mL) for a 2-s duration corresponding 4. Combustion temperatures
to flow rates of 10, 17.5 and 32.5 mL/s. The length of tobacco rod
burned during the puff increased linearly with decreasing Based on the increase in formation rates of CO and HCN at low
circumference. There was a 10% increase in the rod length burned circumferences, Yamamoto et al. (1985) speculated that the puffing
per puff for the 21.5 mm rod compared with the 24.7 mm rod. The temperature increased with decreasing circumference. However,
cross-sectional area decreased by 33% for the 21.5 mm rod this was not supported by the experiments of Robinson (1985) and
compared with the 24.7 mm rod, while the actual weight of tobacco Irwin (1988a).
burned during the puff decreased by approximately 20%. Perfetti Robinson (1985) measured coal surface temperature distribu-
et al. also showed that increasing puff volume increased the puff tions during puffing and smouldering using a scanning infra-red
burn rates to a similar extent at each rod circumference, but the thermovision system. Plain cigarettes with circumferences of 13,
extent of change was not proportional to the increase in puff vol- 20 and 29 mm, at constant packing density, were compared in this
ume. They observed that with a 65 mL puff volume, and particularly study. The peak smoulder temperatures increased linearly (by
for smaller circumference cigarettes, the cigarette paper at the char 80  C) as the circumference decreased from 29 to 13 mm. The peak
line and along the whole length of the rod visibly constricts during puffing temperatures increased from 889  C for the 29 mm ciga-
a puff and then relaxes afterwards. With larger puff volumes, it is rette to 903  C for the 20 mm cigarette, but dropped to 851  C for
likely that increased proportions of the incoming air will by-pass the 13 mm cigarette,. It was speculated that a low peak puff tem-
the burning zone and enter through the cigarette paper. These perature would be expected at higher circumferences as the air
observations and proposed mechanism are consistent with the lack flow is spread over a larger cross sectional area and the burn
of proportionality between the increase in rod length burned dur- behaviour more closely approaches the smouldering state. Rob-
ing the puff and the increase in puff volume. inson suggested that the reduction in peak puffing temperature for
The rod length and weight of tobacco burned during the puff the 13 mm cigarette was due to a higher proportion of the puff
may also be influenced by the extent of peripheral heat loss. Greater passing through the burning coal rather than through the paper at
peripheral heat loss from smaller circumference tobacco rods is the periphery of the combustion zone, suggesting different com-
expected due to the greater surface area-to-volume ratio. The faster bustion conditions for this sample.
linear burn rate which occurs with decreasing circumference also Coal surface temperatures were also reported by Irwin (1988a)
leads to a decrease in puff number. Baker (1973) reviewed several for plain end cigarettes with circumferences of 13, 17, 20, 22,
studies of the effect of circumference on puff number and these 24.75 and 29 mm. Smoulder temperatures increased linearly (by
showed that puff number was directly proportional to the weight of 95  C) as the circumference decreased from 29 to 13 mm. The peak
tobacco in the cigarette (Fig. 3) or, at constant packing density, to puffing temperatures for the 13 and 29 mm circumference ciga-
the cross sectional area. Irwin (1988a) also showed that puff rettes were not significantly different from each other but were
number was proportional to the tobacco weight burned for ciga- significantly lower than those for the 17e24.75 mm circumference
rettes with circumferences in the range 13e29 mm. Baker and cigarettes. This followed the same pattern observed by Robinson in
Irwin's data therefore showed a good correlation between the the previous study (Robinson, 1985). However Irwin noted that the
square of the circumference and the puff number. In contrast, length of the coal increased as the circumference decreased, from
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 115

15 Study
A
14 B
C
13 D

12
Puff Number
11

10

6
0.50 0.75 1.00 1.25 1.50
Tobacco Weight (g)

Fig. 3. Puff number vs tobacco weight (from Baker, 1973). A is a US blend 84 mm filter cigarette, B & C are plain-end, flue-cured blend 72 mm cigarettes, and D is a 70 mm plain-end,
flue-cured lamina cigarette.

which one could conclude that more air enters the burning zone the mock-up test (ASTM, 2004).
through the periphery of the burning zone rather than through the In 2009, Case et al. (2009) evaluated the effects of changes in the
coal as suggested by Robinson (1985). cigarette paper, tobacco and circumference on cigarette ignition
behaviour using the ASTM E2187 standard test method. They
concluded that for cigarettes with either low porosity or banded
5. Cigarette ignition propensity papers, ASTM performance was independent of cigarette circum-
ference in the range 17e26.5 mm. The same conclusion was also
The smouldering properties of cigarettes would also be ex- reached in a later study by Coburn (2010) using a parameter set that
pected to affect their ignition propensities. The science behind included tobacco type, stem level and circumference, also in the
reduced ignition propensity cigarettes was recently reviewed by range 17e26.5 mm.
Baker et al. (2016). Early studies to relate cigarette structural pa- Therefore, any influence of cigarette circumference on cigarette
rameters to their tendency to ignite furniture fabrics were con- ignition propensity is dependent on the test method used, with the
ducted by the Center for Fire Research (National Bureau of current standard test method insensitive to circumference changes.
Standards, Washington, D.C.). Using a test system consisting of a There are no available data on real-world fire incidence as a func-
bench scale furniture mock up and 32 test cigarettes with different tion of cigarette circumference.
construction parameters, it was found that reducing tobacco den-
sity, paper porosity and circumference (21 mm vs 25 mm) caused a
reduction in ignition proclivity (Gann et al., 1987; Krasny et al., 6. Smoke formation processes
1989). It was thought that reducing circumference was effective
because it reduced the weight of tobacco available to burn, as well The smoke formation and transport processes that occur in a
as reducing the contact zone responsible for heat transfer from the burning cigarette have been extensively discussed and reviewed
cigarette to the substrate. However, the test system did not give (e.g. Egerton et al., 1963; Baker, 1973, 1981, 1987; 1999; 2006;
reliable results largely due to variations in the composition of the DeLucia et al., 1978; Muramatsu, 1981; Norman, 1982; Sto € ber,
fabric used. Two simpler test systems were developed. The first 1982; Ingebrethsen, 1986; Jenkins and McRae, 1996; Muramatsu,
used a simplified “mock-up” test, which involved placing the 2005). Essentially, inside a burning cigarette a large variety of
smouldering cigarette on a cotton duck fabric covering a block of chemical and physical processes are occurring simultaneously in an
polyurethane foam. The cigarette was deemed to cause ignition oxygen-deficient environment, with temperatures up to 950  C.
when the burn line in the fabric was more than 10 mm from the The physical processes occurring during combustion can be ratio-
side of the cigarette and no ignition when the burn line was less nalized into two principal mechanistic regionsdtermed the py-
than 10 mm. The cigarette could also be classified as self- rolysis/distillation region and the combustion region or zonedthat
extinguishing when a portion of the tobacco rod remained un- exist inside the cigarette during puffing and smouldering (Fig. 1).
burnt. The second test, the cigarette extinction test method, The vast majority of smoke products are formed in the pyrolysis/
involved placing the smouldering cigarette on a stack of 3, 10 or 15 distillation region, which is immediately downstream of the heat-
layers of filter paper. This latter test measured the propensity of the producing combustion zone. As the smoke aerosol precursors,
cigarette to self-extinguish. which consist of hot vapours and nuclei, leave this region, they cool
In 2004, the American Society of Testing Materials (ASTM) and the vapours condense around the nuclei to form the smoke
adopted the cigarette extinction test (E2187-02b; hereafter E2187) aerosol. Oxides of carbon are formed by both combustion and
as the standard method for ignition propensity due to ongoing thermal decomposition of tobacco constituents, as well as a sig-
problems with obtaining consistent samples of the test fabric for nificant proportion of carbon monoxide being formed by the
116 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

carbonaceous reduction of carbon dioxide. A proportion of the smaller than 0.1 mm, which comprised an increasing proportion of
gases formed in the coal diffuse out into the SS smoke, while the particles at lower circumferences. Fiebelkorn and Robinson
remainder is drawn along the tobacco rod into the MS smoke. The confirmed the importance of flow rate on particle size by adjusting
location of these zones has been determined by mapping internal the puff volumes for each circumference to give a common flow
gas concentrations (Adam et al., 2009; Hertz-Schünemann et al., rate of 35.9 mL s1. Apart from a lower mean number concentration
2015), and by measuring internal density and temperature for the 13 mm circumference cigarette, the mean particle sizes and
changes (Baker, 1981; Li et al., 2016). concentrations were very similar. These changes in particle sizes
The quantities and chemical composition of the MS and SS with circumference are consistent with the higher flow rates and
smoke are influenced by the chemical make-up of the tobacco filler, decreased coagulation through the slimmer cigarettes. They also
the physical and chemical properties of the construction materials indicate perhaps that the laser spectrometer technique is more
used to design the cigarette and the combined effects of the to- sensitive than the conifuge in measuring particle size.
bacco, filter parameters and paper properties on the flow charac- Egilmez compared smoke aerosol properties from four com-
teristics occurring in the burning cigarette. The smoking mercial US brands (Egilmez, 1987) with similar tar deliveries (8 mg/
parameters such as puff volume, duration, and frequency of puffing cig) using a laser spectrometer. Two brands had circumferences of
also determine how much of each smoke component is generated 25 mm and the other two had circumferences of 23 mm and 17 mm.
and distributed into the MS and SS smoke (Baker, 1999). The ultra-slim, 17 mm product had smoke particles with count and
mass median diameters of 0.17 mm and 0.27 mm respectively,
7. Smoke aerosol studies and smoke particle size compared with the three other brands which had similar count and
mass median diameters of 0.19 mm and 0.31 mm respectively. Since
The particle size distribution of the smoke aerosol influences the brands differed in other construction parameters it was not
several important smoke properties such as its interaction with possible to attribute the smaller mean smoke particle size of the
filters and deposition in the human respiratory tract (Sto €ber, 1982; ultra-slim product to circumference alone.
Ingebrethsen, 1986). The undiluted smoke from the burning zone of
the cigarette consists of a highly concentrated cloud of liquid par- 8. MS smoke yields
ticles with number concentrations of about 1010 cm3 and with
diameters ranging from below 0.1 mm to above 1.0 mm. As the Reducing circumference affects both particulate and gas phase
smoke moves along the tobacco rod the smoke particles tend to yields by reducing the total amount of tobacco burnt; this means it
coagulate, which results in a higher average particle diameter, and a will take less time for the tobacco rod to burn and will result in fewer
smaller number concentration. The faster the particles move down puffs. In the case of particulate smoke yields however this is partially
the tobacco rod the less time they have for coagulation and the off-set by a reduction in the filtration efficiency of the tobacco rod
smaller will be the average particle size. Since for a given puff and filter, if present, due to the increased velocity of the smoke
volume the flow rate along the tobacco rod increases with stream (Norman, 1999). For gas phase components the decrease in
decreasing circumference, it would be expected that particle sizes area of the paper and the higher flow rates along the rod will result
would be smaller at lower circumference. Other factors such as in less diffusional losses. An additional factor affecting smoke yields
particle formation, filtration, and evaporation may also have an is the decrease in “dead volume” that occurs as the circumference is
effect, but are thought to be less significant. reduced. For example, it can be calculated that the dead volume for
Jones and Richardson (1971) compared particle size distribu- the first puff of an 84 mm cigarette will change from approximately
tions in smoke from 19 to 31 mm circumference cigarettes using a 17% of a 35 mL puff at 30 mm circumference to approximately 4% of a
conifuge, as a size separating sampling device. Cigarettes were 35 mL puff at 15 mm circumference e this reflects the proportion of
smoked under standard puffing conditions which meant that flow smoke generated within a puff that does not leave the rod during the
rates along the 19 mm cigarette were 2.7 times faster than along the puff in which it is generated. Smoke retained within the rod in this
31 mm cigarette. However there was no significant difference in way can condense out onto tobacco or join the SS plume escaping
mean smoke particle size (0.26e0.29 mm) between the two ciga- the cigarette.
rettes calculated from the number distribution. However,
increasing the puff flow rate from 1.5 to 83 mL/s (a factor of 55) 8.1. MS tar, nicotine and CO yields
decreased the mean particle size by only 46%, suggesting that
particle size is fairly insensitive to circumference. The number There have been a number of published and unpublished in-
concentrations were all in the range 1  1010 to 2  1010 mL1 but dustry studies that have reported yields of the tar (also termed
the breadth of the experimental error prevented any trends being nicotine-free dry particulate matter or NFDPM), nicotine and CO
observed. from cigarettes with different circumferences (Supplementary
Fiebelkorn and Robinson (1988) used a laser spectrometer to Table 1). Unfortunately many of the studies cannot be used to
characterize the smoke aerosols from two series of cigarettes, investigate the effect of circumference alone on smoke yields. Some
differing in blend type with circumferences of 13, 17, 20, 22, 24.75 did not use a standard machine smoking regime such as the ISO
and 29 mm. For both series of cigarettes the count median di- puffing parameters (2 s, 35 mL puff, once a minute) (Ivinson, 1962),
ameters of the particles decreased consistently as circumference some only reported total particulate matter rather than tar
was reduced: from 0.206 mm (at 29 mm) to 0.143 mm (at 13 mm) for (NFDPM) (Lugton, 1971), and some used cigarette samples that did
the flue-cured product and from 0.207 mm (at 29 mm) to 0.153 mm not control parameters other than circumference, such as packing
(at 13 mm) for the blended products. The results for the number density (Wenusch, 1936) or filter pressure drop (Reynolds and
concentrations did not show a clear trend with circumference. For Maya, 1970). Figs. 4e6 show the yields of tar, nicotine and CO
the flue-cured series, for example, number concentrations from three series of cigarettes (Irwin, 1989c; Izac, 1993) made with
increased from 1.56  109 mL1 for the 29 mm product to different blends, with circumferences in the range 13e29 mm and
2.82  109 mL1 for the 22 mm product and then decreased to the same tobacco packing densities within each series. There were
1.88  109 mL1 for the 13 mm product. The apparent reduction in strong positive linear correlations between the yields and circum-
particle numbers at the lower circumferences was ascribed, at least ferences. In the case of CO there were indications that at the highest
in part, to the inability of the spectrometer to detect particles circumferences the yields appear to be reaching a plateau. Similar
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 117

35 Irwin, 1989c (FC)


Irwin, 1989c (US)
Izak , 1993
30

25

Tar (mg/cigarette)
20

15

10

5
15 20 25 30
Circumference (mm)

Fig. 4. Tar vs circumference with linear regressions for three series of cigarettes. The data used from Irwin, 1989c are for NFDPM measured using flue-cured (FC) and US blend (US)
cigarettes. The data from Izac, 1993 are for FTC tar measured using US blend cigarettes.

results were reported by DeBardeleben et al. (1978) for CO from cigarettes with circumferences in the ranges 21 to 26 mm and
cigarettes with circumferences in the range 23e26 mm. The 19e31 mm, respectively.
levelling-off of the CO yields for the higher circumference cigarettes Perfetti et al. (1983) studied puff-by-puff and total deliveries of
was ascribed in part to increased CO diffusion. tar and nicotine from unfiltered tobacco rods with circumferences
Yamamoto et al. (1984) also found linear correlations between in the range 21.5e24.7 mm and constant packing densities. The
tar and nicotine yields and circumference for two sets of filter major conclusions were that a 13% decrease in rod circumference
cigarettes made with either a US blend or Virginia tobacco, and (24.7e21.5 mm), corresponding to a 25% reduction in rod weight,
having circumferences in the range 21.1e25.8 mm. They measured resulted in a 10% decrease in puff count and reductions in yields of
the amounts of tar and nicotine trapped in the 20 mm filter and (FTC Federal Trade Commission) tar and nicotine of 15% and 17%,
10 mm tobacco butt remaining after smoking, and confirmed that respectively.
the amounts of trapped tar and nicotine as a proportion of the total
yields decreased with decreasing circumference as a result of the 8.2. The nicotine/tar ratio
increased smoke velocity. Both Lugton (1971) and Yamamoto et al.
(1984) also showed that the MS yields of tar and nicotine were The study by Perfetti et al. (1983), referred to above, showed a
directly related to the weight of tobacco lost during puffing for small decrease (2.8%) in nicotine/tar ratio as the circumference

3.0 Irwin, 1988a (FC)


Irwin, 1988a (US)
Izak , 1993

2.5
Nicotine (mg/cigarette)

2.0

1.5

1.0

0.5

15 20 25 30
Circumference (mm)

Fig. 5. Nicotine vs circumference with linear regressions for three series of cigarettes. The data from Irwin, 1988a are for flue-cured (FC) and US blend (US) cigarettes. The data from
Izac, 1993 are for US blend cigarettes.
118 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

22.5 Irwin, 1988a (FC)


Irwin, 1988a (US)
Izak , 1993
20.0

17.5

CO (mg/cigarette)
15.0

12.5

10.0

7.5

5.0

15 20 25 30
Circumference (mm)

Fig. 6. CO vs circumference with quadratic regressions for three series of cigarettes. The data from Irwin, 1988a are for flue-cured (FC) and US blend (US) cigarettes. The data from
Izac, 1993 are for US blend cigarettes.

decreases from 24.7 to 21.5 mm. Robinson (1987) found a 32% (Lugton, 1971; Dittrich et al., 2014), cadmium (Irwin, 1989c),
reduction in the nicotine/TPM ratio when circumference was ammonia (Parrish et al., 1989; Siu et al., 2012; Dittrich et al., 2014),
reduced from 29 to 13 mm. Robinson ascribed the increase in organic volatiles (Lugton, 1971; Irwin, 1989c; Randolph and Parrish,
nicotine/TPM with circumference to the lower flow rate in the 1988; Dittrich et al., 2014) and nitrosamines (Irwin, 1988b; 1989b;
wider rods which “enabled the aerosol to absorb the nicotine more Izac, 1993; Dittrich et al., 2014). The effects of circumference on
effectively”. Other studies have not shown a consistent relation these toxicants are summarised in Supplementary Table 1. The
between circumference and nicotine/tar ratios. Both Izac (1993) yields of the majority of toxicants, including nitrosamines, NO,
and Irwin (1988a) found nicotine/tar ratios that increased with phenols, B[a]P, HCN and cadmium, decrease with decreasing ciga-
circumference above 20 mm but also increased as circumference rette circumference in an approximately linear fashion, although
was reduced below 20 mm. yields of NO, HCN and phenols are fairly level at circumferences
greater than 25 mm.
8.3. Machine smoking regime Carbonyl yields, particularly those of formaldehyde, show
distinctly non-linear relationships with circumference. The MS
Greig and Wan (2005) compared MS tar, nicotine and CO de- formaldehyde yields from experimental studies covered by this
liveries from super slim (17 mm) and standard (24.6 mm) review are summarised in Supplementary Table 2. Fig. 7 shows
circumference products when smoked under two different smok- acetaldehyde and formaldehyde yields from 3 studies (Irwin,
ing regimes: ISO - one 35 mL, 2 s puff per minute (ISO, 2012); and a 1989c; Izac, 1993; Yamazaki and Saito, 1978). The yields have
modified intense regime - two 55 mL, 2 s puffs per minute, vents been normalised to those at 17 mm (acetaldehyde) and 25 mm
open. There were no statistically significant differences between (formaldehyde) circumferences to simplify comparisons between
the ratios of tar, nicotine and CO deliveries under the two different studies. Acetaldehyde yields (Irwin, 1989c; Izac, 1993) decreased
smoking regimes for the super slim and standard circumference with circumference but showed a distinctly steeper decline for
products. circumferences below 24 mm. Irwin (1989c) found that formalde-
Perfetti et al. (1983) measured tar and nicotine yields from hyde yields increased slightly as circumferences decreased from 29
different circumference cigarettes smoked at 20, 35 and 60 mL puff to 22 mm, but then decreased as circumferences decreased from 20
volumes. Total per cigarette yields were calculated from individual to 13 mm. Yamazaki and Saito (1978) found no clear trend of
puff by puff deliveries, and the results showed no consistent ratios formaldehyde yields from cigarettes within the narrower circum-
between yields at different puff volumes across the circumference ference range of 23e26 mm.
range 21.5e24.7 mm. The anomalous behaviour of the aldehydes has also been noted
by Case et al. (2005) who reported higher formaldehyde yields for
9. MS smoke toxicants 17 mm vs 25 mm circumference products, and by Parrish et al.
(1989) who observed higher formaldehyde, acetaldehyde and
There have been a number of reports describing the effects of acrolein yields at 20 mm circumference than at 17 and 25 mm.
circumference changes on the yields of various smoke toxicants However it should be noted that these latter two studies used
including carbonyls (Yamazaki and Saito, 1978; Irwin, 1989c; cigarettes that differed in filter efficiencies as well as circumference.
Parrish et al., 1989; Izac, 1993; Case et al., 2005; Dittrich et al., Dittrich et al. (2014) described a series of prototype, reduced-
2014), phenols (Lugton, 1971; Irwin, 1988a, 1989a, 1989c; Dittrich toxicant cigarettes which included three 7 mg ISO NFDPM yield
et al., 2014), nitric oxide (NO) (Irwin, 1988a, 1989c; Izac, 1993; cigarettes manufactured at 17, 21 and 24.6 mm circumferences but
Dittrich et al., 2014), hydrogen cyanide (HCN) (Irwin, 1988a; with the same tobacco blend and packing density. Changes were
1989c; Izac, 1993; Dittrich et al., 2014), benzo[a]pyrene (B[a]P) made to the cigarette paper, filter pressure drop and ventilation
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 119

2.00 Acetaldehyde (Irwin)


Acetaldehyde (Izak)
Formaldehy de (Irwin)
1.75 Formaldehy de (Yamazaki)

Normalised aldehyde yields


1.50

1.25

1.00

0.75

0.50
15 20 25 30
Circumference (mm)

Fig. 7. Relative yields of acetaldehyde and formaldehyde vs circumference using data from Irwin, 1989c; Izac, 1993 and Yamazaki and Saito, 1978. Yields are normalised to 17 mm
circumference (acetaldehyde) and to 25 mm (formaldehyde).

levels to offset the effect of tobacco weight and maintain the 9.2. Toxicant/tar ratios
NFDPM specification. The cigarettes were smoked under Health
Canada Intense (HCI) conditions and MS yields of tar, nicotine, CO Commercial cigarettes are usually designed to yield a given
and 44 smoke toxicants (those mandated to be reported to Health amount of tar (NFDPM) under standard smoking conditions, so it is
Canada) were measured. For all toxicants except pyridine, nitric of interest to compare the ratios of the toxicant to tar. These ratios
oxide and formaldehyde the yields either diminished as circum- would indicate changes in the balance of the smoke chemistry
ference decreased or the differences between yields were not sig- which could be relevant to explaining differences, if any, in bio-
nificant. Pyridine showed a maximum yield at 21 mm logical activity, which are usually expressed as specific activities e.g.
circumference while nitric oxide showed a minimum yield at as activity per unit weight of tar.
21 mm. Of all the toxicants, only formaldehyde yields increased Ratios of toxicant to tar from Irwin (1989c) were calculated and
monotonically as circumference decreased. plotted against circumference. These are shown in Figs. 9 and 10.
The involvement of free-radicals in cell transformation pro- Ratios of CO, CO2, NO, HCN, acetaldehyde and dimethylfuran to tar
cesses has led to the proposal of various mechanisms by which were not significantly correlated with circumference, while ratios
free-radicals in cigarette smoke may be involved in disease pro- of phenols, catechol, and cadmium to tar decreased with decreasing
cesses related to smoking (Church and Pryor, 1985). Free radical circumference (but only significantly for cadmium). In contrast,
concentrations in TPM were measured by Matkin (1988) for plain- ratios of acrolein and formaldehyde to tar increased significantly
end, US blend cigarettes with circumferences of 13, 17, 20, 22, 24.75 with decreasing circumference.
and 29 mm. Whole smoke from the 3rd puff was collected in a Similarly, for the dataset generated by Dittrich et al. (2014) all
quartz cell and free radical concentrations were estimated from the the toxicant/NFDPM ratios for the 7 mg NFDPM products, except for
chemiluminescence of the smoke using a photomultiplier detector. formaldehyde/NFDPM, either decreased with decreasing circum-
Free radical concentrations in the TPM decreased by approximately ference or had maxima or minima at 21 mm. Only formaldehyde/
28% as circumference decreased from 29 to 13 mm. There was no NFDPM showed a monotonic increase as the circumference
explanation for this trend. decreased.
Irwin (1989c) pointed out that as the cigarette circumference
decreased, the ratio of the circumference to the cross-sectional area
9.1. Toxicant yields per gram of tobacco increased, allowing a greater proportion of the tobacco to be in
contact with the incoming air during a puff. Irwin hypothesized
When expressed on a per gram of tobacco burnt basis, Izac that a larger proportion of oxidation reactions, including formation
(1993) found that yields of CO, NO, HCN, water and total alde- of formaldehyde, would be facilitated as the circumference was
hydes increase as the circumference decreases, while TSNA and systematically decreased.
nicotine yields per unit weight of tobacco have no clear relationship To test whether more formaldehyde would be produced in a
with circumference. Irwin (1989c) similarly found that yields of more oxidizing environment, Irwin (1989c) investigated a standard
aldehydes, CO, NO, HCN, phenols and cadmium per unit weight of circumference (25 mm) cigarette smoked in three atmospheres
tobacco increase as circumference is decreased. Fig. 8 shows Irwin's containing 17%, 21% and 25% oxygen in nitrogen (v/v). He found
data for the yields per unit weight of tobacco for formaldehyde, that the yield of tar and nicotine decreased sharply as the level of
acrolein and acetaldehyde normalised to the yield at 29 mm. Yields oxygen in the atmosphere increased, due to much faster burning of
per unit weight of tobacco increase as circumference decreases for the cigarette and a reduced puff count. The ratio of formaldehyde
all three aldehydes but the effect is much stronger for formalde- yield to tar yield increased systematically as the level of oxygen
hyde than for acrolein or acetaldehyde. increased, supporting his hypothesis that MS formaldehyde yields
120 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

Fig. 8. Aldehyde yields per unit weight of tobacco burnt vs circumference. Yields are normalised to those at 29 mm circumference. Data from Irwin, 1989c.

are related to the amount of oxidation occurring. Irwin's (1989c) measurable levels of formaldehyde adducted to DNA in the white
results are consistent with pyrolysis results of Torikai et al. blood cells of smokers and that these were significantly higher than
(2003), who demonstrated that the addition of oxygen (or oxi- those seen in non-smokers, in both cohorts the actual levels were in
dizers) to tobacco significantly increased the pyrolytic formation of the low femtomolar range. It is difficult to determine whether such
formaldehyde (Baker, 2006). low concentrations could have carcinogenic effects and further,
It could also be speculated that the finding of lower concen- without knowledge of the smoking intensity (e.g. number of ciga-
trations of condensate free radicals at lower circumferences rettes smoked per day) in the smoker group it is also difficult to
(Matkin, 1988) might also be related to increased oxidation. gauge the significance of this finding. It is also important to note
Although, as described above, in some studies MS formaldehyde that increased levels of the related cigarette smoke constituent
levels have been shown to be higher in smoke from slim format acetaldehyde have not been detected in the blood of smokers
cigarettes, the toxicological and health implications of this are (McLaughlin et al., 1990). There are differing reports about the ef-
unclear. Although formaldehyde is a known carcinogen, it has not ficiency of aldehyde uptake by smokers. Seeman et al. (2002) re-
yet been demonstrated that, following smoking, it reaches suffi- ported that acetaldehyde was not retained in the lungs and was in
cient levels in the body to have pathological effects. There are very fact mostly exhaled, whereas St. Charles et al. (2013) reported
few data that demonstrate levels of formaldehyde in the blood of almost quantitative retention of formaldehyde and acetaldehyde
smokers. While data published by Wang et al. (2009) demonstrated during puffing. Seeman et al. also suggested that inhaled aldehydes

Fig. 9. Ratios of CO, CO2, HCN, phenols and Cd to NFDPM vs circumference. Data from Irwin, 1988a & 1989c.
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 121

Fig. 10. Ratios of aldehydes, dimethylfuran and catechol to NFDPM vs circumference. Data from Irwin, 1988a & 1989c.

would be quickly metabolised by aldehyde dehydrogenases in the specific nitrosamines (NNN, NAT and NAB) and 4-aminobiphenyl
cells of the lungs (Seeman et al., 2002). Potentially, similar effects and 2-aminonaphthalene. All the other toxicants were either
could explain the extremely low levels of formaldehyde seen in the significantly lower than, or not significantly different to, the bench
blood of smokers. Further studies are required therefore to deter- mark. Toxicant yields from one of the super slim brands were also
mine the actual exposure of smokers of both regular format and compared to those from a single market brand with the same
slim cigarettes to formaldehyde in order to be able to determine length, filter type and blend type but with a circumference of
any pathological consequences of such exposure. 25 mm. In contrast to the bench mark comparison, the super slim
cigarette gave higher yields of formaldehyde, pyridine, acetamide
and phenol per unit tar than the 25 mm circumference cigarette
9.3. Toxicant yields from commercial super slim cigarettes
under ISO smoking conditions, but equal or lower toxicant ratios for
all toxicants under HCI smoking conditions.
As has been stressed previously in this review, when deter-
mining the effect of circumference on smoke composition it is
important to ensure that other cigarette parameters are kept con- 10. SS smoke chemistry
stant. This is unlikely for commercial cigarettes which may have
many different specifications in addition to circumference. One SS yields of tar, nicotine, CO and CO2 decrease with decreasing
approach to avoid this problem is to generate an “average” smoke circumference (Perfetti et al., 1983; Chao, 1985; Case et al., 1987;
composition per unit weight of tar from a large number of different Izac, 1993). These reductions are strongly correlated with the
products, and compare the test product with this average. This is weights of the tobacco in the cigarette rod (Warren, 1987), which, at
the essence of the “benchmark” approach used by Health Canada to constant packing density, are also proportional to the square of the
estimate the yields of 31 toxicants from Canadian products based circumference. The data of Perfetti et al. (1983) from cigarettes with
on their tar deliveries (Health Canada, 2000). The Canadian circumferences of 21.5e24.7 mm, and Chao (1985) from cigarettes
benchmark is generated from the toxicant yields of a minimum of with circumferences of 13e22 mm show strong linear correlations
28 brands obtained under both ISO and HCI smoking conditions. Siu between the square of the circumference and SS tar and SS nicotine.
et al. (2012) compared the toxicant/tar ratios generated from the Table 1 shows the relationship between the smoke yields of tar,
2010 Canadian benchmark with ratios measured for six super slim nicotine CO and CO2 in MS smoke (MS) and SS for non-filtered
(17 mm circumference) brands (Health Canada, 2014). Since the cigarettes of constant packing density across a range of circumfer-
other benchmark Canadian cigarettes have circumferences of ences using data from Perfetti et al. (1983). All MS and SS yields
24.5 ± 1.0 mm this comparison was expected to show the effect of decrease with decreasing circumference, but the ratios of SS/MS
reduced circumference on toxicant/tar ratios. Four of the six super yields decrease only very slightly with decreasing cigarette
slim brands had flue-cured blends and two had US style blends. circumference.
Two of the flue-cured blends had charcoal filters and the other There have been several studies of smoke toxicants in SS. Izac
cigarettes had standard cellulose acetate filters. Under ISO smoking (1993) reported TSNA yields per unit weight of tobacco for ciga-
conditions the toxicant/tar ratios for all six super slim products rettes with circumferences in the range 17e27 mm. For NAT and
were either significantly lower than the benchmark, including NNN, SS yields per g tobacco were independent of circumference.
acetaldehyde (4/6 brands), butyraldehyde (4/6 brands) and pro- For NNK, yields per g tobacco peaked at 24 mm circumference and
pionaldehyde (4/6 brands), or were not significantly different from were lower at other circumferences.
the benchmark, including formaldehyde (6/6 brands). Under HCI Parrish et al. (1989) measured SS yields of benzene, toluene and
smoking the super slim brands had significantly greater yields of the volatile aldehydes for two sets of cigarettes made at 17, 20 and
ammonia (6/6), nicotine (4/6) and formaldehyde (4/6). In addition 24.8 mm circumference. One set was made with conventional
the two US blended products had higher yields of the tobacco cigarette paper and the other with a low SS paper containing
122 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

Table 1 and the SS yields of 44 smoke toxicants (those mandated to be


Yields and ratios of sidestream (SS) and mainstream (MS) tar, nicotine, CO and CO2 reported to Health Canada) were measured. The SS yields of all the
for non-filtered cigarettes with constant packing density. Data from Perfetti et al.,
1983.
toxicants, except for formaldehyde, decreased with decreasing
circumference. Formaldehyde yields increased as circumference
Analyte Circumference (mm) decreased from 24.6 to 21 mm before decreasing to their lowest
21.5 22.8 23.7 24.7 level at 17 mm circumference.
MS
Tar (mg/cig) 24.1 25.7 26.2 28.3
11. Biological activity
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 Whole smoke and/or condensate from cigarettes with different
Puff Number 7.5 7.7 8.0 8.3 circumferences have been subjected to a number of different tests
SS for bioactivity. These have included in vitro mutagenic and clasto-
Tar (mg/cig) 18.8 20.4 22.5 25.4
Nicotine (mg/cig) 2.96 3.37 3.78 4.33
genic testing of the condensate (Izac, 1993; Irwin, 1989c; Massey
CO (mg/cig) 36.9 38.5 44 47.5 and Barnes, 1987; Massey and Godden, 1987; Massey, 1989; 1991;
CO2 (mg/cig) 309 337 389 420 Mladjenovic et al., 2013; Coggins et al., 2013), testing for acute
SS/MS ratios toxicity of whole smoke and condensate using micro-organisms
Tar 0.78 0.79 0.86 0.90
(Lugton, 1971; Coggins et al., 2013), in vivo tumorigenicity testing
Nicotine 1.93 2.03 2.12 2.34
CO 1.02 1.00 1.14 1.16 of condensate using mouse skin painting (Lugton, 1971; Clapp et al.,
CO2 22.9 21.9 25.5 26.1 1977; Dontenwill et al., 1977; Smith, 1990) and whole smoke using
All cigarettes had a packing density of 0.287 g cm3. MS yields were measured under
inhalation toxicology (Smith, 1990).
standard FTC conditions. SS yields were measured by the so-called “fishtail chim-
ney” method (Coresta, 2011).
11.1. In vitro mutagenicity and clastogenicity tests

There have been several reports of the effect of circumference


magnesium hydroxide (Mg(OH)2) filler. Benzene and toluene SS change on the Ames test which determines the mutagenicity of
yields decreased linearly with the weight of tobacco in the cigarette condensate to different strains of Salmonella Typhimurium bacteria
(and with the square of circumference). However formaldehyde, (Massey and Godden, 1987; Irwin, 1989c; Massey, 1989; Izac, 1993;
acetaldehyde, acrolein and butyraldehyde all gave distinctly non- Mladjenovic et al., 2013; Coggins et al., 2013). The bacteria are
linear correlations with tobacco weight. Plots of acetaldehyde, exposed to various dilutions of smoke condensate, which is
formaldehyde and acrolein are shown in Fig. 11. The reason for the collected either on a Cambridge filter or in an impaction trap.
non-linearity is unknown, but Irwin's hypothesis (Irwin, 1989c) of The activity of the condensate is usually reported on a per unit
increased smoke oxidation at low circumferences would be weight of condensate basis and is then referred to as “specific ac-
consistent with these results. tivity”. However, in some cases, activities are reported on a unit tar
Dittrich et al. (2014) described a series of prototype cigarettes (NFDPM) basis. Both of these normalisation approaches decouple
which demonstrated a number of different approaches for reducing the impact of different quantities of smoke in the assays, allowing
toxicant yields. Included in this study were three 1 mg ISO NFDPM any influence of circumference to be clearly observed.
yield cigarettes manufactured at 17, 21 and 24.6 mm circumfer- Studies have consistently shown reductions in specific activity
ences but with the same tobacco blend, packing density, paper type with reducing circumference using both TA98 and TA100 strains of
and filter tow. These were smoked under ISO smoking conditions bacteria (Izac, 1993; Coggins et al., 2013). For example, Massey

4000 SS Formaldehy de Control


SS Formaldehy de Test
SS A cetaldehy de Control
SS A cetaldehy de Test
SS A crolein Control
Aldehyde yields (ug/cigarette)

3000 SS A crolein Test

2000

1000

0
400 500 600 700 800 900 1000
Tobacco Weight (mg/cigarette)

Fig. 11. SS yields of formaldehyde, acetaldehyde and acrolein vs tobacco weight. Data from Parrish et al., 1989. “Control” cigarettes have conventional paper. “Test” cigarettes have
low-SS Mg(OH)2 papers.
K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126 123

(1989) determined specific Ames activities (strain TA98 with S9 chorioallantoic membrane of fertile hens’ eggs after smoke
activation) of condensates from flue-cured and US-style cigarettes condensate had been applied for 4 days (BAT, 1969c). There were no
with circumferences of 13, 17, 20, 22, 24.75 and 29 mm. Specific significant differences in specific activity between smoke conden-
mutagenic activities fell by 49% and 39% for the flue-cured and US sates from different circumference cigarettes. However, on a per
blended series, respectively, when the circumference was reduced cigarette basis, the smoke condensate from cigarettes of smaller
from 29 to 13 mm. Part of the reason for the reduced activity may circumference were significantly less active than from the larger
be due to the higher flow rates through the cigarette, which result products, which reflects the lower weights of condensate from
in less effective filtration of the more volatile, and less mutagenic, these cigarettes.
smoke components by the tobacco rod and filter (Robinson, 1987). More recently, Coggins (Coggins et al., 2013) reported the results
Massey (1989) tested the magnitude of this effect by modifying the of the neutral red uptake assay on the condensates from cigarettes
puff volume drawn through the cigarettes in order to produce equal with circumferences of 17, 21 and 23.9 mm. Relative to the 27.1 mm
linear air flow at all circumferences. This resulted in the cigarettes circumference (control) cigarette, the specific toxicities (1/EC50) on
with circumferences of 22e29 mm having specific activities that a per weight of smoke condensate basis decreased from 1.22 for the
were not significantly different. However the lowest circumference 23.9 mm cigarette, to 0.99 for the 21 mm cigarette and to 0.83 for
cigarettes (13 and 17 mm) still had significantly lower specific ac- the 17 mm cigarette.
tivities than those with higher circumference. Massey speculated In general, data from Ames tests and from other in vitro toxi-
that at very low circumferences the higher ratios of circumference cological tests indicate that as the circumference of a cigarette
to cross-sectional area may provide more oxygen during puffing as decreases (yielding lower cigarette smoke condensate deliveries),
suggested by Irwin (1989c) to explain the relatively higher form- the toxicological activity of the smoke decreases above and beyond
aldehyde/tar ratios for lower circumference cigarettes. This is the amount of smoke generated by these cigarettes.
supported by findings that increased oxygen in the combustion
zone results in condensate with reduced Ames activity (Massey, 11.3. In vivo tests
1989).
Mladjenovic et al. (2013) compared the Ames mutagenicities of A few studies have assessed the effect of circumference on the
11 Canadian cigarette brands using Salmonella strains TA98, tumorigenicity of smoke using mouse skin painting (Clapp et al.,
YG1041 and YG5185. The cigarettes had different blends, filter 1977; Dontenwill et al., 1977; Smith, 1990).
types, ventilation levels and circumferences. Five brands were su- In a study by the Tobacco Research Council (Smith, 1990), a
per slim with circumferences of 16.8 ± 0.2 mm and 6 brands had decrease in tumour-forming specific activity was found for smoke
circumferences of 24.5 ± 1.0 mm. After taking into account the condensate from cigarettes of 19 mm circumference as compared
differences in blend types it was concluded that the super slim with condensate from products of 25.3 mm and 31.5 mm circum-
brands had significant lower mutagenicities than the 24.5 mm ference. There was no difference between the condensates from the
products. 25.3 and 31.5 mm cigarettes.
The influence of circumference on the clastogenic activity of Clapp et al. (1977) found that the specific activities of conden-
smoke condensate (i.e. the number of chromosome aberrations per sates from 23 mm cigarettes were less active than those from
mg of condensate) in human lymphocytes has also been investi- 25.4 mm cigarettes. This was found for both 100% tobacco ciga-
gated (Massey, 1991). The specific activity of a flue-cured 13-mm rettes and for blends with tobacco substitute (NSM).
cigarette condensate was less than that of a 24.75 mm cigarette Dontenwill et al. (1977) compared tumorigenicities of conden-
condensate of the same blend composition. sates from cigarettes with circumferences of 21.7 mm, 25.5 mm and
28.9 mm. Condensate from the 21.7 mm cigarette was significantly
11.2. In vitro cytotoxicity tests lower in specific activity than that from the 25.5 mm cigarette.
Condensates from the 25.5 mm and 28.9 mm product were not
The effect of circumference on the acute toxicity of smoke was significantly different.
investigated using a number of short term tests involving micro-
organisms applied to smoke from cigarettes with circumferences of 11.4. Inhalation toxicity
19, 22, 25, 28 and 31 mm (Lugton, 1971). The paramecium hanging-
drop test measures vapour phase toxicity and involves passing Smith (1991) reported inhalation toxicological testing of ciga-
successive puffs of smoke past a water droplet containing the ciliate rette smoke from cigarettes with circumferences of 13, 17, 20, 25
(BAT, 1969a). The number of puffs required to kill the ciliate is and 29 mm circumference. The 6-week inhalation study on rats
recorded. In this test, no significant difference was observed be- involved exposing the animals to 7.9e8.6 mg/L of TPM on a twice
tween cigarettes of different circumference implying no difference daily basis. There were no consistent differences in response be-
between toxicities of each puff. tween the treatment groups.
The Tetrahymena solution test measures the cytotoxicity per Overall, it seems clear that as cigarette circumference decreases,
cigarette of various dilutions of whole smoke in aqueous solutions the specific tumorigenic activity of cigarette smoke also decreases.
of tetrahymena vorax (BAT, 1969b). The lowest circumference cig- However the specific toxicity of the smoke during inhalation is not
arettes had smoke with lower cytotoxicities in line with the TPM affected by circumference.
yields. The Tetrahymena particulate-phase test measures the spe-
cific cytotoxicity of the tar (BAT, 1970). It involves treating Petri 12. Mouth level exposure studies
dishes containing Tetrahymena vorax with different concentrations
of tar in acetone. The compounds responsible for this cytotoxicity As described above, many studies have documented lower MS
are thought to be chemically different from those that kill the smoke yields of a wide range of chemicals in cigarette smoke from
microorganism when whole smoke is employed. Tar from the slim format cigarettes. However, this does not necessarily mean
lowest circumference cigarettes showed a significantly lower spe- that smoking these cigarettes reduces either the human exposure
cific activity than from the highest circumference cigarettes. to these chemicals or modifies the risks associated with smoking.
The chorioallantoic membrane test was used to examine the Although a person's mouth level exposure to smoke can be deter-
toxicity of smoke condensate by measuring the thickness of the mined from puff duplicators, analysis of discarded butts after
124 K. McAdam et al. / Regulatory Toxicology and Pharmacology 82 (2016) 111e126

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)

Romania 1 17.0 7.1 ± 2.1c 0.70 ± 0.19c


4 24.6 11.9 ± 2.9b 1.04 ± 0.28b
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
Russia 1 24.6 8.9 ± 3.4d 0.98 ± 0.35cd
1 17.0 9.4 ± 3.2d 0.86 ± 0.28d
4 24.6 16.7 ± 5.1b 1.53 ± 0.48a
4 17.0 13.5 ± 4.2c 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±4 mm in length and had carbon filters.


a,b,c,d
Values within a study with same alphabetical character are not significantly different (P < 0.05).

human smoking is a much less invasive and more rapid technique. cases, increases relative to tar as circumference decreases. In terms
A more recent improvement in butt analysis is the part filter of bioactivity, in vitro specific mutagenic, cytotoxic and tumorigenic
analysis method in which only the mouth-end portion of the filter, activities decrease as circumference decreases in the range 29 to
downstream of the ventilation holes, is used for analysis (BAT, 13 mm. The specific toxicities of the smoke to the rodent respira-
2016). In this portion, the filtration efficiency is relatively con- tory tract are not sensitive to circumference changes. The increases
stant irrespective of typical puff flow rates of humans and also in formaldehyde relative to tar and the reduction in some of the
minimizes butt length effects (e.g. nicotine condensation) on specific bioactivities of the condensate with decreasing circumfer-
filtration efficiency. Therefore, the estimations of human smoking ence appear to be related at least in part to a more oxidizing
cigarette yields are better correlated to human smoking conditions burning zone. Recent studies on MLE to smoke amongst smokers of
than previous whole-filter methods (St. Charles et al., 2009). slim and conventional circumference products found that exposure
In the first of two studies of slim cigarettes performed using this to tar and nicotine was either lower in smokers of 17 mm circum-
technique, Ashley et al. (2011) examined mouth level exposure ference cigarettes compared with smokers of conventional 25 mm
(MLE) to tar and nicotine in cohorts of Romanian smokers of king circumference cigarettes or not significantly different. It must be
size cigarettes with circumferences of either 25 mm (conventional) emphasized that although reduced circumference is a cigarette
or 17 mm (super slims). No significant differences were found be- design feature that can be used in conjunction with other param-
tween the MLE to ‘tar’ and nicotine in smokers of the conventional eters to help reduce certain MS and SS smoke toxicants and some
and slim cigarette over a range of different ISO tar yields (1 mg, measures of bioactivity, there is no evidence that slim cigarettes per
4 mg and 7 mg ISO tar per cigarette). This suggested that cigarette se are any less harmful than cigarettes with higher circumferences.
circumference had no influence on smokers' exposure to tar or
nicotine. In a second and similar follow-up study performed in Declaration of interest
Russia (Ashley et al., 2014), MLE to tar was found to be similar for
smokers of 1 mg ISO tar yield products, but lower for smokers of K. McAdam, A. Eldridge, I.M. Fearon, C. Liu, A. Manson, J. Murphy
4 mg and 7 mg super slim cigarettes, compared to conventional and C. Proctor are employees of British American Tobacco (In-
format cigarettes. MLE to nicotine was lower in smokers of 4 mg vestments) Ltd. A. Porter is a paid consultant for British American
super slim compared to conventional cigarettes, but not for other Tobacco (Investments) Ltd. Preparation of the manuscript was
tar bands. The results for both the Romanian and Russian studies funded by British American Tobacco (Investments) Ltd.
are summarised in Table 2. These studies demonstrate that
smokers' exposure to tar and nicotine are either similar or lower in Appendix A. Supplementary data
smokers of slim format cigarettes when compared to those seen in
smokers of conventional cigarettes. It must be noted however that Supplementary data related to this article can be found at http://
this does not imply any difference in disease risk associated with dx.doi.org/10.1016/j.yrtph.2016.09.010.
smoking different styles of cigarette and further studies would be
required in order to evaluate such differences in risk, if any.
Transparency document

13. Conclusions Transparency document related to this article can be found


online at http://dx.doi.org/10.1016/j.yrtph.2016.09.010.
This review of academic and industry-based studies has shown
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