De Minimus Non Curat Lex - Virtual Thresholds for Cancer Initiation by Tobacco Specific Nitrosamines - Prospects for Harm Reduction by Smokeless Tobacco

Abstract

Whereas the impact of tobacco specific nitrosamines in smokers is obscured by the presence of numerous other carcinogens and promoters, for smokeless tobacco virtually all the carcinogenic potential is associated with 4-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). In some countries exposure to smokeless tobacco with extremely high nitrosamine concentrations have been found to induce cancers in the head-neck region, whereas three recent large epidemiological studies failed to detect any such risk with respect to Swedish low-nitrosamine snuff. This review deals with quantitative aspects of DNA adduct formation from NNN and NNK in relation to the background levels ubiquitously found in healthy humans without known exposures to either tobacco or alkylating agents. The lack of significant increases of pro-mutagenic O6-methylations and DNA pyridyloxobutylations seen in smokers, as well as the negative outcome of the Swedish epidemiological studies, can be expected on basis of extrapolation of the dose response relationships found in rodents to actual exposures to NNK and NNN in Swedish snuff or from smoking. Sweden has the lowest prevalence of male smokers and smoking related diseases in the Western World, which has been ascribed to the fact that more than 20% of the grown up male population uses snuff. Smokeless tobacco represents an inexpensive and effective alternative to nicotine delivering products like nicotine patch, spray or gum. Considering that all other tobacco products are freely marketed, the ban on low-nitrosamine snuff in all countries in EU except Sweden is difficult to defend on either medical or ethical grounds.

Systematic review of the relation between smokeless tobacco and cancer in Europe and North America

“…Furthermore, details such as the type of ST used, and duration and frequency of use, are often not considered. The products used vary by country and over time, and increased risks seen in older studies for some cancers may not reflect the risks of more modern products, with reduced nitrosamine levels [ 128 ]. For most cancers, the number of effect estimates available is really too limited to allow a very detailed examination of variation in risk by such factors as type of product used, current or former use, country and sex.…”

Potential carcinogenic effects of cigarette smoke and Swedish moist snuff on pancreas: a study using a transgenic mouse model of chronic pancreatitis

“…In our study, during the 15-month observation period, we did not detect more advanced preneoplastic or neoplastic lesions in the pancreas of Elastase-IL-1b mice treated with tobacco. Although Snus intake in these mice was comparable with those of Snus users, 19,48,49 the amount of tobacco intake in TS-treated mice may be lower than found in human cigarette smokers. Given the fact that most human pancreatic ductal adenocarcinoma occurs after the fifth decade of life, our study, similar to others, is potentially limited by the length of the observation period in mice, and a possible need for exposure to a higher concentration of tobacco carcinogens.…”

Ramuan “Puree” Sebagai Alternatif Subtitusi Rokok; Studi Fenomenologi Kearifan Lokal Masyarakat Angata, Konawe Selatan

“…Di Eropa Tengah dan Timur tingginya penggunaan nikotin tanpa asap terdapat pada produk permen karet nikotin, serta semprotan nikotin, yang terdaftar sebagai produk farmasi merupakan alternatif murah dan ekonomis. Tembakau dengan kadar nitrosamine rendah, yang secara kinetis nikotin lebih mirip dengan merokok, menawarkan kemungkinan lain untuk terapi pengganti nikotin untuk berhenti merokok 7 .…”