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Global surveillance of oral tobacco products: total nicotine, unionised nicotine and tobacco-specific N-nitrosamines
  1. Stephen B Stanfill1,
  2. Gregory N Connolly2,
  3. Liqin Zhang1,
  4. Lily T Jia3,
  5. Jack E Henningfield4,
  6. Patricia Richter5,
  7. Tameka S Lawler1,
  8. Olalekan A Ayo-Yusuf6,
  9. David L Ashley1,
  10. Clifford H Watson1
  1. 1Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Emergency Response and Air Toxicants Branch, Atlanta, Georgia, USA
  2. 2Harvard University School of Public Health, Boston, Massachusetts, USA
  3. 3Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Organic Analytical Toxicology Branch, Atlanta, Georgia, USA
  4. 4The Johns Hopkins University School of Medicine and Pinney Associates, Bethesda, Maryland, USA
  5. 5Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, Georgia, USA
  6. 6Department of Community Dentistry, Faculty of Health Sciences, University of Pretoria, South Africa
  1. Correspondence to Stephen B Stanfill, National Center for Environmental Health, 4770 Buford Highway, Atlanta, Georgia 30341, USA; sstanfill{at}


Objective Oral tobacco products contain nicotine and carcinogenic tobacco-specific N-nitrosamines (TSNAs) that can be absorbed through the oral mucosa. The aim of this study was to determine typical pH ranges and concentrations of total nicotine, unionised nicotine (the most readily absorbed form) and five TSNAs in selected oral tobacco products distributed globally.

Methods A total of 53 oral tobacco products from 5 World Health Organisation (WHO) regions were analysed for total nicotine and TSNAs, including 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), using gas chromatography or liquid chromatography with mass spectrometric detection. Unionised nicotine concentrations were calculated using product pH and total nicotine concentrations. Fourier transform infrared spectroscopy was used to help categorise or characterise some products.

Results Total nicotine content varied from 0.16 to 34.1 mg/g product, whereas, the calculated unionised nicotine ranged from 0.05 to 31.0 mg/g product; a 620-fold range of variation. Products ranged from pH 5.2 to 10.1, which translates to 0.2% to 99.1% of nicotine being in the unionised form. Some products have very high pH and correspondingly high unionised nicotine (eg, gul powder, chimó, toombak) and/or high TSNA (eg, toombak, zarda, khaini) concentrations. The concentrations of TSNAs spanned five orders of magnitude with concentrations of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranging from 4.5 to 516 000 ng/g product.

Conclusions These data have important implications for risk assessment because they show that very different exposure risks may be posed through the use of these chemically diverse oral tobacco products. Because of the wide chemical variation, oral tobacco products should not be categorised together when considering the public health implications of their use.

  • Oral tobacco
  • nicotine
  • tobacco-specific N-nitrosamines
  • carcinogenicity
  • addiction potential
  • addiction
  • carcinogens
  • co-substance use
  • smokeless tobacco products
  • toxicology

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  • Funding This work was funded by the U.S. Government, Department of Health and Human Services. This study was also funded internally at the Centers for Disease Control and Prevention, with funds directly provided by the U.S. federal government.

  • Competing interests JEH serves as a consultant through Pinney Associates to GlaxoSmithKline Consumer Healthcare on an exclusive basis regarding matters relating to smoking cessation, has a financial interest in a potential new nicotine replacement product, and has provided expert testimony against the tobacco industry. The other authors declare they have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.