This significant decrease relative to the levels measured in the original version of Marlboro Snus resulted in the lower amount of NNN + NNK present in a single since portion of Marlboro Snus, even as the size of the pouches increased over time (Table 1). It should be noted that while the users of smokeless tobacco products that are sold in loose form, such as many varieties of moist snuff, can select the size of the portion used for a single application; in the case of packaged smokeless products, the manufacturer controls the dose, and the increase of the constituent level per single pouch will most likely lead to an increase in the consumers�� exposure to these constituents. Other product characteristics, such as moisture content and tobacco particle size, can affect the degree of constituent extraction from the tobacco pouch and its absorption through the oral mucosa.

For example, the observed increase in the moisture content of Marlboro Snus (Table 1) can facilitate the extraction of nicotine and potentially NNN and NNK from the large-pouch version of this product. Tobacco particle size is not measured in our laboratory; therefore, we cannot comment on potential changes of this parameter. Individual consumer characteristics such as pH of saliva and patterns of use are also important determinants of individual exposure to nicotine and TSNA from a smokeless tobacco product. The results of biomarker-based studies might become available in the future, allowing comparison of the relative intake of nicotine and/or NNN and NNK from Camel Snus and Marlboro Snus pouches of various sizes.

The lack of a specifically designed study to compare the amounts of constituents in pouches of various sizes is the major limitation of this report. The constituent levels analyzed here were originally measured for different studies, without the intention of comparing products purchased in various years. Therefore, there is a large variation in the number of available samples for each pouch size and/or year of purchase. Nevertheless, the number of samples was sufficient to conduct statistically meaningful comparisons among pouches of different sizes. In summary, we report here our observation of an increase in nicotine content per single pouch of Camel Snus and Marlboro Snus, and an increase in TSNA content in Camel Snus pouches, as a result of an increase in pouch sizes for both products between 2006 and 2010.

While the health consequences of these changes are still to be understood, the observed tendency implies that unaware consumers might be exposed to even higher levels of these constituents, as the new oral tobacco products are being further modified in the AV-951 future. This finding stresses the importance of tobacco product regulation, ingredient disclosures, and the provision of accurate information to consumers, so that they can make informed decisions.