Concentrations of the Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Sidestream Cigarette Smoke Increase after Release into Indoor Air: Results from Unpublished Tobacco Industry Research

  title={Concentrations of the Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Sidestream Cigarette Smoke Increase after Release into Indoor Air: Results from Unpublished Tobacco Industry Research},
  author={Suzaynn F. Schick and Stanton A. Glantz},
  journal={Cancer Epidemiology Biomarkers \& Prevention},
  pages={1547 - 1553}
  • S. SchickS. Glantz
  • Published 1 August 2007
  • Medicine
  • Cancer Epidemiology Biomarkers & Prevention
Research has shown that the toxicity of sidestream cigarette smoke, the primary constituent of secondhand smoke, increases over time. To find potential mechanisms that would explain the increase in sidestream smoke toxicity over time, we analyzed unpublished research reports from Philip Morris Co. using the internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other Web sites. Unpublished research from Philip Morris… 

Figures and Tables from this paper

Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards

It is shown that residual nicotine from tobacco smoke sorbed to indoor surfaces reacts with ambient nitrous acid (HONO) to form carcinogenic tobacco-specific nitrosamines (TSNAs), which represents an unappreciated health hazard through dermal exposure, dust inhalation, and ingestion.

Evaluation of tobacco specific nitrosamines exposure by quantification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human hair of non-smokers

For the first time, NNK is present in hair samples from non-smokers in concentrations much higher than any other tobacco specific nitrosamine, and may provide a good estimation of cancer risk associated with exposure to secondhand smoke.

Urine Cotinine Underestimates Exposure to the Tobacco-Derived Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Passive Compared with Active Smokers

Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking, suggesting a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure to the toxic constituents of secondhand tobacco smoke.

Thirdhand smoke causes DNA damage in human cells.

It is demonstrated for the first time that exposure to THS is genotoxic in human cell lines, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity.

Cotinine Underestimates Exposure to the Tobacco-ived Lung Carcinogen 4-( Methylnitrosamino )-1-( 3-Pyridyl )-B & P utanone in Passive Compared with Active Smokers

The discrepancy between cotinine levels in relation to disease risk comparing versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that c nicotine is oviding an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke.

Extensive Metabolic Activation of the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Smokers

The results of this study show for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for ∼86% of total urinary excretion of NNK metabolites.

Comparison of urine cotinine and the tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and their ratio to discriminate active from passive smoking.

Both urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure when biomarkers are measured while a person has ongoing exposure to tobacco smoke.

Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos

The results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.



Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines: chemistry, biochemistry, carcinogenicity, and relevance to humans.

Evidence is presented that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increase risk of lung cancer, especially pulmonary adenocarcinoma, in smokers.

Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

The results of the available carcinogen derived biomarker studies provide biochemical data which support the conclusion, based on epidemiologic investigations, that SHS causes lung cancer in non-smokers.

Sidestream cigarette smoke toxicity increases with aging and exposure duration

Using total particulate material as the measure of smoke exposure, aging sidestream cigarette smoke for at least 30 minutes increases its toxicity fourfold for 21 day exposures and doubles the toxicity for 90 day exposures, relative to fresh sidestREAM smoke.

Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke

Fresh sidestream smoke at concentrations commonly encountered indoors is well above a 2 μg/m3 reference concentration (the level at which acute effects are unlikely to occur), calculated from the results of the INBIFO studies, that defines acute toxicity to humans.

The carcinogenicity of environmental tobacco smoke.

It was concluded that ETS is a pulmonary carcinogen in strain A/J mice and feeding of butylated hydroxytoluene during ETS exposure did not modulate lung tumor development.


Male Sprague-Dawley rats were exposed to aged and diluted sidestream smoke (ADSS), used as a surrogate for environmental tobacco smoke (ETS), at concentrations of 0.1, 1, or 10 mg of particulates/m3, and the only pathological response observed was slight to mild epithelial hyperplasia in the rostral nasal cavity, in the exaggerated exposure group only.

The carcinogenic potential of the gas phase of environmental tobacco smoke.

The gas phase of ETS is as carcinogenic as is full ETS and the carcinogenicity of the gas phase may be due to some as yet unidentified, yet highly potent carcinogens or by placing a substantial, possibly free radical-mediated oxidative stress on the lung.

Respirable Particles and Carcinogens in the Air of Delaware Hospitality Venues Before and After a Smoking Ban

  • James L. Repace
  • Medicine, Environmental Science
    Journal of occupational and environmental medicine
  • 2004
This air-quality survey demonstrates conclusively that the health of hospitality workers and patrons is endangered by tobacco smoke pollution, and Smoke-free workplace laws eliminate that hazard and provide health protection impossible to achieve through ventilation or air cleaning.

Lung Tumor Response in Strain a Mice Exposed to Tobacco Smoke: Some Dose-Effect Relationships

The shape of the dose-response curve and a comparison with previous data suggest that cigarette smoke is only a comparatively weak mouse lung carcinogen.