A comparative study of the mutagenicity of various types of tobacco products

doi:10.1016/j.yrtph.2007.05.003

Regulatory Toxicology and Pharmacology

Volume 48, Issue 3, August 2007, Pages 320-330

https://doi.org/10.1016/j.yrtph.2007.05.003 Get rights and content

Abstract

Toxicological data are an important aspect of tobacco product characterization. In this study, TPM (Total Particulate Matter) (three replicates) was collected from cigarettes [five brands, ISO conditions: puff volume, 35 mL; duration, 2 s; interval, 60 s (35/2/60)], cigars (two brands, 45/2/30), cigarillos (two brands, 35/2/60), bidis (two brands, 45/2/30), and pipe tobacco (two brands, 50/2/12). TPM was extracted from the Cambridge filter pad using dimethyl sulfoxide (DMSO). Smokeless tobacco (ST) (six brands) was extracted with DMSO using an ultrasonic homogenizer. Both types of extracts were filtered and stored at −80 °C. All extracts were analyzed for humectants, water and nicotine. Mutagenic activity was assessed per OECD guideline 471 using Salmonella typhimurium TA98+S9 and TA100+S9. TA98+S9 response (specific activity expressed as revertants/mg nicotine) was greatest for the cigarette fabricated with dark, air-cured tobaccos. Average product responses with TA98+S9 based on nicotine and relative to cigarettes (excluding dark tobacco) were cigars, 242%; cigarillos, 238%; bidis, 91%; and pipe tobacco, 44%. ST response was not significant for TA98+S9. Corresponding values for TA100+S9 were cigars, 189%; cigarillos, 155%; pipe tobacco, 130%; bidis, 114% and ST, 34%. ST TA100+S9 response ranged from a low of 501 to a high of 8547 revertants/mg nicotine, depending on ST composition.

Introduction

In the latter decades of the twentieth century, US cigarette consumption began to decline on account of increased health concerns and taxes. Conversely, sales of other smoking products such as cigars increased after declining for many years (Wehlburg, 1999). Sales of smokeless tobacco products, which had also declined, increased, particularly sales of wet snuff (Surgeon General, 1986). Part of this increase in the sales of noncigarette tobacco products was believed due to consumer perceptions that smokeless tobaccos and cigars were safer than cigarettes. The US Congress mandated warning labels on smokeless tobacco products in 1986. One of those warnings was, “This product is not a safe alternative to smoking” (CDC, 2000). The basis for such warnings was evidence that use of smokeless tobacco products had been associated with oral cancer and other diseases and such products were addictive (Surgeon General, 1986). Warnings were put on cigar products in 2000 (CDC, 2000).

While most experts see little difference in the health risks associated with smoking noncigarette tobacco products versus smoking cigarettes, there has been increased debate about the health risks associated with smokeless tobacco products over the last decade as exemplified by Nilsson’s risk assessment on snuff dipping (Nilsson, 1998). One of the reasons for debate has been that there are many different kinds of smokeless tobacco products used worldwide. Traditionally, three types of smokeless tobacco products have been sold in North America: (1) chewing tobacco (looseleaf, plug, twist); (2) dry snuff; and (3) wet snuff (Surgeon General, 1986, Wahlberg and Ringberger, 1999). Each of these three types of products is different, chemically and physically, from each other and each of them differs in many respects from smokeless tobacco products made outside North America (Nilsson, 2006, Nilsson, 1998, Rodu and Jansson, 2004). Some have advocated use of smokeless tobacco products as a substitute for cigarettes for those who cannot or will not stop smoking (Levy et al., 2004). However, others feel that the health risks of such a proposition are too high and that only medicinal nicotine should be used (Hatsukami et al., 2004). While there is considerable epidemiological evidence supporting the use of certain smokeless tobacco products as has been pointed out by experts in the field (Rodu and Godshall, 2006, Nilsson, 2006, Rodu and Jansson, 2004, Bates et al., 2003), there is a lack of bioassays to distinguish smokeless tobacco products deemed less hazardous from those that could be more hazardous. In addition, it would also be desirable to have bioassays to compare the hazards of smokeless tobacco products with smoking products to assist public health officials in making policies on use of smokeless tobacco products. Furthermore, it would be desirable to be able to put the results of such bioassays on a common metric to compare all tobacco products whether smoking or not.

There are no indications that use of smokeless tobacco products has been associated with smoking-related nonneoplastic lung disease such as chronic obstructive pulmonary disease (Anczak and Nogler, 2003). Furthermore, there is no environmental tobacco smoke (ETS) generated by use of smokeless tobacco. The debate has been focused on the relationships between smokeless tobacco use and various cancers. At least one expert has related all associations between smokeless tobacco and cancer to the tobacco specific nitrosamines (TSNAs) in the products (Nilsson, 2006). However, the TSNA levels in contemporary, commercial smokeless tobacco products as well as mainstream cigarette smoke are thought to be too low to contribute to the mutagenicity as measured by the Ames assay especially in the presence of nicotine (Brown et al., 2001, Grasso et al., 1996, Deaton, 1987). On the other hand, extracts of smokeless tobacco products have been found to be mutagenic (Nair et al., 2004, Niphadkar et al., 1996, Stamm et al., 1994, Jansson et al., 1991, Guttenplan, 1987). Some authors have reported correlations between results of various in vitro assays for mutagenicity such as the Ames Salmonella/microsome mutagenicity assay with the results on rodent carcinogenicity studies (Mortelmans and Zeiger, 2000, Kim and Margolin, 1999a). Thus, there have been numerous reports over the years of the Ames assay being used to determine and compare the mutagenicity of tobacco smoke condensates as noted in the reviews by DeMarini, 2004, Massey, 2002. In addition, and as noted above, several researchers had determined the Ames activity of extracts of smokeless tobacco products. However, none of these studies had been designed to compare conventional cigarette products, with other contemporary smoking products as well as contemporary smokeless tobacco products available in the North American market. In the study reported herein, a number of smoking and smokeless tobacco products were obtained and characterized both chemically and with the Ames assay. Furthermore, the results from the Ames assay have been put on a per-unit nicotine basis to permit comparison of smoking and smokeless products on a per unit nicotine basis.

Section snippets

Experimental

Smoking products evaluated included several types of filtered cigarettes (dark air-cured, blended, flue-cured), cigarillos, cigars, bidis (made in India), and pipe tobacco. Three types of smokeless tobacco products were evaluated: (1) pouched and loose wet snuff typical of products sold in US and Canada; (2) tableted and loose dry snuff reportedly made with specially cured, low-nitrosamine tobaccos; and (3) two types of smokeless tobacco products from India. The first of these was a gutkha,

Results

The results for the mainstream smoke chemical analyses are shown in Table 1. The results obtained are typical for the products analyzed. The TPM from the dark tobacco cigarette and from the CIM-7 flue-cured reference cigarette did not contain detectable glycerin or propylene glycol. This is consistent with what is known about the products. Likewise, the lack of propylene glycol in the TPM from the KY2R4F reference cigarette is consistent with the published formulation.

The results for the

Discussion

Mutagenicity generally is not an acceptable attribute for a product intended for human consumption. However, some foods and beverages (e.g., broiled meat and coffee) show some evidence of mutagenic activity (Sugimura, 2000). It may be argued that nutrition is essential for life and some foods need to be cooked to minimize the levels of pathogens and toxins, and mutagens arising from such cooking may not present an unreasonable risk of disease. On the other hand, items consumed for pleasure,

Conclusions

Our initial objective for this work was to characterize the mutagenic response for a range of smoked and smokeless tobacco products. We found, although it is far from a perfect solution, that we could compare the mutagenic potency of mainstream smoke condensate from smoking articles with that of smokeless tobacco products if we based our comparisons on mutagenic potency expressed on a nicotine basis. Thus, we were able to compare the mutagenicity of TPM, measured in terms of revertants per

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^☆: Presented, in part, at the 58th Tobacco Science Research Conference, 19–22 September 2004, Winston-Salem, North Carolina, USA.

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A comparative study of the mutagenicity of various types of tobacco products☆

Abstract

Introduction

Section snippets

Experimental

Results

Discussion

Conclusions

Food Chem. Toxicol.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Prev. Med.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Mutat. Res.

Regul. Toxicol. Pharmacol.

Food Chem. Toxicol.

Toxicology

Cancer Lett.

Mutat. Res.

J. Food Prot.

Tobacco cessation in primary care: maximizing intervention strategies

Clin. Med. Res.

In vitro antimicrobial activity of dimethylsulfoxide

Appl. Microbiol.

European Union policy on smokeless tobacco: a statement in favour of evidence based regulation for public health

Tob. Control

The reducing property of tobacco smoke. 2. The influence of smoking vehicle with particular reference to pipe

Beiträge zur Tabakforschung

Foods pyrolysis and risk of toxicity [French]

Cah. Nutr. Diet.

The effectiveness of Salmonella strains TA100, TA102, and TA104 for detecting mutagenicity of some aldehydes and peroxides

Mutagenesis

Mainstream and sidestream yields of “tar”, nicotine and CO from various types of cigars when smoked under a variety of conditions

Tob. Sci. Res. Conf.