, 2011), as well as by the epidemiological evidence that smokeless tobacco products contaminated with high levels of NNN cause oral cancer (Gupta, Murti, & Bhonsle, 1996; IARC, 2007; Stepanov, Hecht, Ramakrishnan, & Gupta, 2005). In summary, our results demonstrate that the carcinogenic (S)-enantiomer of NNN predominates in cigarette tobacco and smoke, moist inhibitor Tofacitinib snuff, and novel smokeless tobacco products currently marketed in the United States. Given the potential role of (S)-NNN as a causative agent for esophageal and oral cancers associated with tobacco use, these results support the importance of reduction, or ideally elimination, of NNN in tobacco products. FUNDING This study was supported by grants CA-141631, CA-81301, and CA-135884 from the U.S.

National Institutes of Health and by National Cancer Institute Contract HHSN261201000544P. DECLARATION OF INTERESTS There are no competing interests. ACKNOWLEDGMENT We thank Bob Carlson for editorial assistance.
Waterpipe tobacco smoking has in recent years become prevalent across the globe. A waterpipe consists of a head, body, water bowl, and corrugated hose. It is often smoked with a moist, sweetened, and flavored tobacco mixture known as ma��assel, with burning charcoal placed atop as a heat source. Thus, in addition to smoke constituents originating from the tobacco, waterpipe smoke also contains charcoal combustion emissions. While a common perception among users is that waterpipe is relatively safe, it has been shown to deliver to the user large quantities of polycyclic aromatic hydrocarbons, aldehydes, tar, nicotine, and carbon monoxide (Al Rashidi, Shihadeh, & Saliba, 2008; Sepetdjian, Shihadeh, & Saliba, 2008; Shihadeh & Saleh, 2005).

Also, waterpipe smoke can be a major source of furans specially 5-(hydroxymethyl)-2-furaldehyde (Schubert, Bewersdorff, Luch, & Schulz, 2012). Phenols are listed as priority pollutants by the U.S. Environmental Protection Agency due to their high toxicity (Yan & Quan, 2009). In particular, polyphenolic compounds such as catechols and hydroquinones and their methyl derivatives that are present in tobacco smoke are important tumor promoters and provoke an increase in metastasis of lung cancer (Gopalakrishna, Chen, & Gundimeda, 1994; Hoffmann, Djordjevic, & Hoffmann, 1997).

Other health impacts caused by phenolic compounds have been linked to genotoxic activities and cardiovascular effects (Fowles & Dybing, 2003; Harvey, Howe, Lynch, & Drug_discovery Rees, 2005; Leanderson & Tagesson, 1990). The generation of phenols in cigarette mainstream smoke is attributed to the distillation, depolymerization, and decomposition of tobacco components during pyrolysis. The precursors of catechol formation are the polyphenols such as quinic acid and quinic acid derivatives present in tobacco.