A comparison of the mutagenicity of mainstream cigarette smoke condensates from a representative sample of the U.S. cigarette market with a Kentucky reference cigarette (K1R4F).

The Salmonella mutagenicity assay has been used to investigate the mutagenicity of cigarette smoke and cigarette smoke condensate. The Kentucky reference (K1R4F) cigarette is designed to be representative of full-flavor, low-tar cigarettes sold in the U.S. and to serve as a reference standard for comparative studies on the chemistry and biological activities of cigarette smoke and condensate. The objective of this study was to determine if the mutagenicity of mainstream smoke condensate from the K1R4F, as measured by the Salmonella mutagenicity assay, is representative of the mutagenic activity of U.S. cigarettes. Mainstream smoke condensates prepared in dimethyl sulfoxide from the K1R4F and 73 brand styles (representing greater than 70% of the total U.S. cigarette market) were assayed using Salmonella typhimurium TA98 and TA100 (+S9) at concentrations of 0, 25, 50, 75, 100, 125 and 250 micrograms/plate. Revertants/mg condensate were determined by calculating the slopes of the dose-response curves using linear and nonlinear regression models. Revertants/cigarette were determined by multiplying the revertants/mg condensate by the mg condensate/cigarette. No significant differences (p > 0.05) were observed between the mean mutagenicity of U.S. market and K1R4F mainstream smoke condensates in terms of revertants/mg condensate or revertants/cigarette. Increased variability in mutagenicity was observed among the U.S. brands versus that of the K1R4F. This is not surprising since variability among the U.S. brands would be expected to have both measurement error and brand style variability while the K1R4F variability contains only the measurement error portion. These results demonstrate that the K1R4F is a representative model for the U.S. cigarette market in comparative Salmonella mutagenicity studies using mainstream smoke condensates.

Analysis of cytogenetic effects in bone-marrow cells of rats subchronically exposed to smoke from cigarettes which burn or only heat tobacco.

The genotoxic effects of 90-day nose-only exposures to smoke from new cigarettes, which heat but do not burn tobacco (New), or from reference cigarettes, which burn tobacco, were evaluated in Sprague-Dawley rats by examining the cytogenetic endpoints of sister-chromatid exchanges (SCE), chromosome aberrations, and micronuclei in bone-marrow cells. The concentrations of wet total particulate matter (WTPM) and carbon monoxide in the smoke from both cigarette types were similar. The mainstream smoke from both New and reference cigarettes was adjusted to WTPM concentrations of approx. 200 and 400 micrograms/l for low and high smoke exposure. Rats were exposed to smoke 1 h per day, 5 days per week for 13 consecutive weeks. Inhalation of smoke by the exposed animals was confirmed by analysis of blood carboxyhemoglobin and plasma nicotine. Examination of bone-marrow cells following the final day of exposure showed that smoke from neither the New nor reference cigarette induced a positive response in the SCE, chromosome aberration, or micronucleus assays in rats.