Tobacco Additives

6. What else can enhance addictiveness of tobacco products?

The SCENIHR opinion states:

Parts of cigarettes, like the paper and filter have technical features which affect the constitution of main-stream and side-stream smoke.

Considering the natural origin of tobacco leaves, their content will, both qualitatively and quantitatively, depend on the season, local weather conditions and geographical origin. Consumers do not like to smoke a product that changes over time, i.e. smoking a constant product is preferred. In order to produce a constant product, i.e. to mask the batch to batch variation in taste, tobacco companies use a large variety of additives in the manufacture of tobacco products. In addition, the tobacco companies strongly prefer to maintain the same TNCO values (tar, nicotine and carbon monoxide) of their products. To achieve consistency in TNCO values, tobacco producers change, amongst others, the ventilation of the products. The ventilation through the filter can be increased by punching more (or wider) ventilation holes. The ventilation of a cigarette can also be changed by using commercially available cigarette paper wraps with another grade of porosity.

Relevant technical characteristics of cigarettes are the following:

• Ventilation of the paper (paper porosity);
• Ventilation holes in the filter;
• Ventilation holes in the paper wrap;
• Packing of tobacco (dense or loose); and
• Geometry (length, diameter).

Ventilation

Large efforts have been made by the tobacco industry to investigate the effect of ventilation on the size distribution of the smoke aerosol. Depending on the size, the smoke particles enter and deposit at different levels of the airways (upper or lower airways). The purpose of this research was either to enhance the absorption of nicotine, to decrease the toxic potential of the product or to manipulate the taste of the smoke.

The main effect of ventilation is the dilution of the tobacco smoke. As such, the concentration of smoke components is reduced which not only leads to a lower dose of nicotine, but also to a lower concentration of other (toxic) components. It appears, however, that smokers compensate for the lower dose of nicotine per puff (due to increased ventilation) by increasing their puff volume, puff frequency, and deeper inhalation of the smoke (Jarvis et al. 2001, Scherer 1999). Many other smokers consciously or unconsciously block a part of the ventilation holes with their fingers so that more concentrated smoke is inhaled.
Another feature of ventilation is that it may affect the particle size and particle size distribution of the smoke aerosol, i.e. increasing the ventilation is supposed to decrease the mean particle size of the aerosol. It is difficult to assess whether an increase in ventilation indeed reduces the particle size as only few studies are reported in publicly available literature.

Technical limitations

It is difficult to determine the size of the particles and their distribution in cigarette smoke, mainly because the half-life of the particles is very short (0.1-1 sec). Rapid ageing of the aerosol results in larger particles as they have time to coalesce, i.e. a secondary aerosol containing larger particles at the expense of smaller particles is rapidly formed (Harris and Kay 1959). Therefore, only sophisticated on-line sampling and detection allows a proper measurement of the particle distribution of the smoke aerosol. Obviously, these techniques require large financial resources and highly qualified technical personnel.

A number of variables other than ventilation may affect the particle size; moisture of the cigarette (relative humidity), puff volume, puff number (e.g. first or last puff), butt length, length of the cigarette, electrostatic charges, etc. Different unities are used in the studies to express the size of the particles (mean diameter, count median aerodynamic diameter, mass median aerodynamic diameter) which hampers quantitative comparison of the data. The aerosol is produced during burning, i.e. directly behind the burning cone at the tip of the cigarette the superheated vapour condenses and forms an aerosol; the longer the aerosol stays in the cigarette, the larger the size of the particles.

Due to the number of different particle sizing methods, instrumentation and sampling and detection techniques applied, as well as differences in the cigarettes and smoking conditions, variable results are found and the results of different investigations are difficult to compare. Important limiting factors for many techniques are low time of resolution and the ageing of the smoke. Over time various methods have been developed to improve the accuracy of the measurements.

Smoke particles

Particle size may be relevant for the absorption of nicotine into the bloodstream. Cigarette smoke particle size has generally been reported with mass median diameter (MMD) in the size range of 0.3-0.5 µm and count median diameter (CMD) in the range of 0.2-0.4 µm (Bernstein 2004, Wayne et al. 2008a). Particles larger than 1 µm are mostly trapped within the cigarette, whereas ultra-fine particles (less than 0.1 µm - nano-particle range) probably will adhere to the surface of the paper, tobacco and filter, or coagulate into larger particles (Stratton et al. 2001), see section 3.5.4. Differences in particle size found in many studies were quite small and some internal tobacco documents concluded that the measurable influence of conventional design changes was insignificant (Philip Morris 1991, Wayne et al. 2008a). Of the four variables applied by Philip Morris to change the size of the particles (filler, filter, paper and ventilation) only ventilation had any significant effect (Cox et al. 1992). In addition, butt length and puff volume affect the size of the particles. There is a clear trend of decreased size of the particles at shorter butt lengths; the average size at 20 mm was 0.29 µm and at 55 mm it was 0.34 µm. Cox et al. (1992), taking all the variables mentioned above into account, reported deviations of about 10 to 30%. Surface mean diameter increased from 0.32 to 0.42 µm when the ventilation was increased from 0 to 60%. Based on their results, Cox et al. (1992) suggested that aerosol coagulation in the cigarette rod is the main mechanism for change in particle size.

Bernstein (2004) reviewed the available data of the tobacco smoke particulates which go back to 1950s. The main findings include:

• No difference in particle size between plain (non-filter) and filter cigarettes.
• Particle size depends on puff number (e.g. first vs. last puff).
• Relative humidity of the tobacco does not affect or only marginally affects particle size.
• Aged tobacco smoke contains larger particles than fresh smoke.

Considering all the studies reviewed by Bernstein, the size of the smoke particles range roughly from 0.17 to 0.60 µm, either expressed as CMD or MMD. A study by McCusker et al. (1983) compares mass median aerodynamic diameter of ultra-low-tar, low-tar and medium-tar rated cigarettes (with and without filter). Particle size was less than 0.6 µm and not affected by the cigarette filters. Among the 10 brands tested ventilation ranged from 22 to 94%. The mass median aerodynamic diameter ranged from 0.36 µm to 0.56 µm, but did not correlate with ventilation efficiency. The number of particles was, however, reduced by 20–90% by applying the commercial filters and the particles were present in the higher puff numbers. Interestingly, blocking of the ventilation holes on the filters of ultra-low-tar cigarettes increased the particle concentration. This is explained by the longer residence time (longer transit time from cone to filter) of the newly formed particles in the cigarette rod.

As mentioned, only sophisticated on-line sampling and detection allows a proper assessment of the particle size and distribution. Moreover, the relevance of ultra-fine particles for nicotine absorption has only been taken seriously for the last two decades; therefore, most of the older studies did not focus on the presence of ultra-fine particles.

Recently, using on-line measurement of the particle size (range measured 5–1000 nm), Adam et al. (2009) reported that non-ventilated cigarettes smoked under an intense regime, which includes blocking the ventilation holes resulted in a count median diameter of 0.18 µm, whereas 70% ventilated cigarettes smoked under a milder standard smoking regime led to a diameter of 0.28 µm. The particle size of mainstream smoke of Virginia cigarettes, smoked under a standard smoking regime, was 0.22 µm and 0.25 µm at 0 and 70% ventilation, respectively. For the intense smoking regime the respective particle sizes were 0.18 and 0.22 µm. Interestingly, when the ventilation was increased from 0 to 70% the total number of particles decreased dramatically from 2.3×1012 to 0.3×1012, and the total mass of particles dropped from 17.2 to 2.3 mg (standard smoking regime). In another recent paper by Gowadia et al. (2009) the particle size (mass median aerodynamic diameter) was found to be approximately constant (0.9–1.0 µm) for three different puffing regimes. The smoke was collected in a conditioning chamber and the particle size distribution was determined by UV spectrometry.

The particle size of waterpipe smoke was shown to be somewhat smaller than that of cigarette smoke. Monn et al. (2007) reported waterpipe smoke particle median diameter of 40 nm in a full smoking set containing charcoal, tobacco and water; the smoke of the heated tobacco alone ranged from 10 nm to 200 nm while the burning of charcoal was mostly responsible for the particles smaller than 50 nm. Fromme and colleagues found two phases of particle emission during a waterpipe session; when the charcoal was lit, the particle diameter was around 100 nm and during the smoking session it decreased to 17 nm (Fromme et al. 2009). Daher et al. (2010) found similar particle sizes to the Monn study in side-stream smoke from waterpipes, which were significantly smaller than particle sizes in side-stream smoke from cigarettes with a median diameter of 139 nm and a large number of particles smaller than 100 nm.

Deposition of particles

Although the size of the particle is an important factor for the deposition in the lung, the relationship between particle size and deposition in the lung is complex and factors other than size alone, such as respiration rate, depth of inhalation and flow rate, affect lung deposition (Sarangapani and Wexler 2000).

In figure 1 the relative deposition of particles (dependent on the aerodynamic diameter) in humans is depicted. Particles larger than 1 µm will mainly deposit in the extra-thoracic region. Smaller particles will deposit in different regions, but the general statement that smaller particles deposit deeper in the lung is not entirely true. Very small particles (a few nm) will mainly deposit in the extra-thoracic region. Peak alveolar deposition is around 30-20 nm and becomes less important at sizes less than 8-9 nm (ICRP 1994, Oberdörster et al. 2005). The question whether the ultra-fine particle size is relevant for mainstream tobacco smoke is unanswered. From a theoretical point of view removal of ultra-fine particles is to be expected due to adherence to the surface of the paper or to the tobacco and filter, or due to coagulation into larger particles (Stratton et al. 2001) (see section 3.5.3), however this needs to be confirmed experimentally.

Other points of concern in the inhalation of ultra-fine particles are the translocation of these particles: (1) from the lumen of the lung to the circulation; and (2) from the olfactory nerve endings in the nose to the brain. These two events have been described for several solid nanoparticles in the lungs of animals and humans (Kreyling et al. 2002, Nemmar et al. 2002), and in the noses of rodents (Oberdörster et al. 2002). These phenomena have not been shown for tobacco smoke derived particles which are not solid nanoparticles (although combustion derived particles have been studied in the lung); therefore, only theoretical/hypothetical considerations can be made (which fall outside the scope of this opinion).

Light cigarettes as an example of cigarettes with high ventilation
The best known application of changing ventilation is the development of light cigarettes. Light cigarettes have been marketed as products with a lower health risk as they should deliver less tar and other toxic compounds in the smoke inhaled. As will be described in detail in section 3.10.1 many smokers of light cigarettes inhale the smoke deeper and increase the number of puffs, so the health risks are probably not lower than for smokers of regular cigarettes (Frost et al. 1995). Animal studies have shown that self-administration of a low dose of nicotine at a high frequency gives a more reinforcing effect as compared to self-administration of a higher dose at a low frequency (in this comparison total dose self-administered is the same) (Harris et al. 2008, Harris et al. 2009, O’Dell et al. 2007).

Conclusions on technical characteristics
A number of technical characteristics of cigarettes influence the content of different substances in the smoke and the size of smoke particles. The so-called TNCO values (tar, nicotine and CO) are determined by, amongst other things, ventilation (paper, filter), the packing of the tobacco and the geometry of the cigarettes. Smokers usually compensate for a lower dose of nicotine by increasing puff volume and frequency, and by deeper inhalation. Data obtained in animal studies suggest that cigarettes with high ventilation (often described as “light” or “low tar”) may favour addiction to nicotine in the smokers of these products, because of an increased smoking frequency. The particle size of smoke aerosol of commercial cigarettes is around 0.4 to 2 µm. A large fraction of ultrafine particles (<0.1 µm) probably adheres to the surface of the paper or the filter, or coagulates into larger particles, and will thus not be present in the smoke as such. The small smoke particles (submicron meter range) will enter the lower airways and alveoli, while larger particles (micron meter range) will be deposited increasingly in the upper airways. Considering the manufacturing of cigarettes, the change of the technical characteristics of cigarettes may affect the mean particle size and, therefore, the distribution of the smoke aerosol. However, based on the limited publicly available information, it seems that exposure to nicotine cannot be substantially increased by altering the particle size of the smoke aerosol.