<abstract xmlns="http://www.w3.org/1999/xhtml"><p>A new reference cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chemistry and toxicity of the two reference cigarettes under the International Organization for Standardization (ISO) machine smoking conditions, and to further compare mainstream smoke chemistry and toxicological activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI) smoking conditions.</p><p>The <italic>in vitro</italic> cytotoxicity and mutagenicity was determined in the neutral red uptake assay, the <italic>Salmonella</italic> reverse mutation assay, and the mouse lymphoma thymidine kinase assay. Additionally, a 90-day nose-only inhalation study in rats was conducted to assess the <italic>in vivo</italic> toxicity. The comparison of smoke chemistry between the two reference cigarettes found practically the same yields of total particulate matter (TPM), ‘tar’, nicotine, carbon monoxide, and most other smoke constituents. For both cigarettes, the <italic>in vitro</italic> cytotoxicity, mutagenicity, and <italic>in vivo</italic> toxicity showed the expected smoke-related effects compared to controls without smoke exposure. There were no meaningful differences between the 2R4F and 3R4F regarding these toxicological endpoints. The assessments for the 3R4F cigarette by smoking regimen found as a trivial effect, due to the higher amount of smoke generated per cigarette under HCI conditions, an increased yield of toxicant and higher toxicological activity per cigarette. However, per mg TPM, ‘tar’, or nicotine, the amounts of toxicants and the <italic>in vitro</italic> toxicity were generally lower under HCI conditions, but the <italic>in vivo</italic> activity was not different between the two machine smoking conditions. Overall, as the main result, the present study suggests equivalent smoke chemistry and <italic>in vitro</italic> and <italic>in vivo</italic> toxicity for the 2R4F and 3R4F reference cigarettes.</p></abstract>

A new reference cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chemistry and toxicity of the two reference cigarettes under the International Organization for Standardization (ISO) machine smoking conditions, and to further compare mainstream smoke chemistry and toxicological activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI) smoking conditions.The in vitro cytotoxicity and mutagenicity was determined in the neutral red uptake assay, the Salmonella reverse mutation assay, and the mouse lymphoma thymidine kinase assay. Additionally, a 90-day nose-only inhalation study in rats was conducted to assess the in vivo toxicity. The comparison of smoke chemistry between the two reference cigarettes found practically the same yields of total particulate matter (TPM), ‘tar’, nicotine, carbon monoxide, and most other smoke constituents. For both cigarettes, the in vitro cytotoxicity, mutagenicity, and in vivo toxicity showed the expected smoke-related effects compared to controls without smoke exposure. There were no meaningful differences between the 2R4F and 3R4F regarding these toxicological endpoints. The assessments for the 3R4F cigarette by smoking regimen found as a trivial effect, due to the higher amount of smoke generated per cigarette under HCI conditions, an increased yield of toxicant and higher toxicological activity per cigarette. However, per mg TPM, ‘tar’, or nicotine, the amounts of toxicants and the in vitro toxicity were generally lower under HCI conditions, but the in vivo activity was not different between the two machine smoking conditions. Overall, as the main result, the present study suggests equivalent smoke chemistry and in vitro and in vivo toxicity for the 2R4F and 3R4F reference cigarettes.

Mainstream Smoke Chemistry and <italic>in Vitro</italic> and <italic>In Vivo</italic> Toxicity of the Reference Cigarettes 3R4F and 2R4F

Philip Morris International Operations, Philip Morris Products S.A., Rue des Usines 90, 2000 Neuchâtel, Switzerland

Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstr. 3, 51149 Cologne, Germany

Histovia GmbH, SchoeneAussicht 5, 51491 Overath, Germany

Philip Morris International R&D, Philip Morris Research Laboratories bvba, Grauwmeer 14, 3001 Leuven, Belgium

Contributions to Tobacco & Nicotine Research

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mainstream Smoke Chemistry and  and  Toxicity of the Reference Cigarettes 3R4F and 2R4F

A new reference cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare...

Mainstream Smoke Chemistry and in Vitro and In Vivo Toxicity of the Reference Cigarettes 3R4F and 2R4F

Data publikacji: 30 gru 2014

Zakres stron: 316 - 335

Otrzymano: 01 wrz 2011

Przyjęty: 24 sty 2012

DOI: https://doi.org/10.2478/cttr-2013-0912

© 2012 Beiträge zur Tabakforschung International

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.