A comprehensive evaluation of the toxicology of cigarette ingredients: aromatic carbonyl compounds

Abstract

Context: Aromatic carbonyls are typically used in the processing or flavoring of tobacco used in the manufacture of cigarettes.

Objective: A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing different added levels of aromatic carbonyl compounds.

Materials and methods: Ten aromatic carbonyl compounds, nine of which have been reported in tobacco or in tobacco smoke, were added individually to experimental cigarettes at three different levels. The tenth compound, not found naturally in tobacco, was 2-phenoxyethyl isobutyrate. The lowest target inclusion level was 100 ppm and the highest was 10,000 ppm. Smoke from each of the 10 experimental cigarette types was evaluated using analytical chemistry, in vitro cytotoxicity, and mutagenicity testing. For one of the compounds, ethyl vanillin, a 90-day smoke inhalation study using rats was also performed.

Results: Smoke chemistry was effectively unchanged by the addition of any of the compounds. Cytotoxicity, assessed by the neutral red uptake assay and using both gas-vapor and particulate phases of smoke, was unaffected by the addition of any of the test compounds. Mutagenicity, assessed by five strains of Salmonella typhimurium treated with smoke condensate, also was unaffected by any of the test compounds. In the rat inhalation study, there were effectively no differences between cigarettes without added ethyl vanillin and cigarettes containing ~8000 ppm of ethyl vanillin.

Conclusion: Even at the exaggerated inclusion levels in cigarette tobacco used in these tests, no adverse toxicological responses occurred for any of aromatic carbonyl compounds tested.

Keywords::

• Cigarette ingredients
• aromatic carbonyl compounds
• smoke chemistry
• in vitro and in vivo toxicology

Acknowledgements

The authors acknowledge the study directors at the IIT Research Institute and at Philip Morris Research Laboratories, as well as Mark A. Higuchi, Stephanie U. Knighten, Ranulfo Lemus, and Lisa M. Merriman. The authors also acknowledge the editorial assistance of Eileen Y. Ivasauskas of Accuwrit Inc. The authors thank Lonnie T. Rimmer for his work in preparing the supplemental material.

Declaration of interest

Dr. C.R.E. Coggins is a consultant for Altria Client Services and as such was compensated for his contribution to this work.