Toxicological evaluation of an electrically heated cigarette. Part 3: Genotoxicity and cytotoxicity of mainstream smoke

Introduction:
This text reports the results of a study comparing the genotoxicity and cytotoxicity of an electrically heated cigarette (EhC) to the University of Kentucky Reference Cigarette 1R4F. The study uses the Salmonella reverse mutation assay and the neutral red uptake cytotoxicity assay to evaluate the biological activity of the smoke from these two cigarettes. The study also discusses the differences in smoke composition between the two cigarettes and their implications for the observed biological activity.

Key Points:

* The study used the Salmonella reverse mutation assay and the neutral red uptake cytotoxicity assay to evaluate the genotoxicity and cytotoxicity of smoke from the EhC and the 1R4F cigarettes.
* The TPM (total particulate matter) from the EhC was up to 90% lower in mutagenicity than that of the 1R4F when calculated on an equal TPM basis.
* When calculated on an equal TPM basis, TPM from the EhC was 40% less active relative to the 1R4F in terms of cytotoxicity.
* When calculated on a per cigarette basis, the cytotoxicity of both the TPM fraction and the water-solubles in the gas/vapor phase of smoke from the EhC was ca. 80% lower relative to the 1R4F.
* The study used a set of Salmonella typhimurium his- tester strains with different types of mutations in the histidine operon to evaluate the mutagenicity of cigarette smoke.
* The cytotoxicity assay was conducted with the BaLB/c 3T3 cell line, which responds to cytotoxic compounds in a broad dynamic range.
* The mutagenicity determination and cytotoxicity assay were carried out in accordance with the Organization for Economic Cooperation and Development Guideline 471 and the INVITTOX protocol, respectively.

Main Message:
The study found that the EhC produces smoke with substantially lower biological activity as measured in the bacterial mutagenicity and neutral red uptake cytotoxicity assays. These reductions in biological activity can be explained partially by the reduction of certain individual smoke constituents that are usually associated with smoke-related mutagenic or cytotoxic response. however, it is also assumed that the reduction in the amount of these smoke constituents runs parallel to the reduction in the amounts of other, more biologically active constituents in the same classes. The study highlights the importance of evaluating the biological activity of cigarette smoke in addition to its chemical composition to better understand the potential health risks associated with smoking.

Tewes, F. J., T. J. Meisgen, D. J. Veltel, E. Roemer, and G. Patskan. “Toxicological Evaluation of an Electrically heated Cigarette. Part 3: Genotoxicity and Cytotoxicity of Mainstream Smoke.” Journal of applied Toxicology 23, no. 5 (September 2003): 341–48. https://doi.org/10.1002/jat.925.