A comparison of in vitro toxicities of cigarette smoke condensate from Eclipse cigarettes and four commercially available ultra low-"tar" cigarettes.

Eclipse is a cigarette that primarily heats rather than burns tobacco. R.J. Reynolds Tobacco Company (RJRT) has previously reported the results of in vitro toxicity studies comparing Eclipse with University of Kentucky 1R5F and 1R4F reference cigarettes. To characterize the differences between Eclipse and very low yielding/ultra low-"tar" (vULT) tobacco-burning cigarettes, RJRT conducted a comparative evaluation of the genotoxicity and cytotoxicity of mainstream cigarette smoke condensate (CSC) from Eclipse and three vULT tobacco-burning cigarettes (Now 83 Box, Merit Ultima and Carlton Soft Pack) as well as the leading ultra low-"tar" (ULT) brandstyle (Marlboro Ultra Lights) under four smoking regimens: (1) FTC-35 ml puff volume every 60 s for a 2 s duration (35/60/2); (2) 50/30/2, 0% vents blocked; (3) Massachusetts-45/30/2, 50% vents blocked; (4) Canadian-55/30/2, 100% vents blocked. Ames testing indicated that Eclipse CSC was less (P<0.05) mutagenic than CSC from the four cigarettes under all smoking regimens when compared on a revertants per mg Total Particulate Matter (TPM) basis. When mutagenicity was calculated on a revertants per cigarette basis the mutagenicity of Eclipse CSC was lower (P<0.05) than the mutagenicity of Merit Ultima, Carlton Soft Pack, and Marlboro Ultra Lights, regardless of the puffing regimen. On a per cigarette basis, the calculated mutagenicity of Eclipse was higher (P<0.05) than Now 83 Box cigarettes in the FTC and 50/30/2 regimens but lower (P<0.05) in the Massachusetts and Canadian regimens. Eclipse CSC was less (P<0.05) cytotoxic as measured in the neutral red assay (based on EC(50) values-microg TPM/ml media) than the CSC from the four test cigarettes regardless of the regimen used. Collectively, these data demonstrate that the toxicity of CSC from Eclipse is significantly reduced relative to the activity of CSC from the tested vULT cigarettes and the Marlboro Ultra Lights.

Inhibition of rat respiratory-tract cytochrome P-450 isozymes following inhalation of m-Xylene: possible role of metabolites.

Xylene is used as a solvent in paints, cleaning agents, and gasoline. Exposure occurs primarily by inhalation. The volatility and lipophilicity of the xylenes make the lung and nasal mucosa the primary target organs. m-Xylene (m-XYL) has been shown to alter cytochrome P-450 (CYP) activity in an organ- and isozyme-specific manner. The purpose of this work was to determine if the metabolism of m-XYL to the inhibitory metabolite m-tolualdehyde (m-ALD) is the cause of inhibition of CYP isozymes following in vivo inhalation exposure to m-XYL (100, 300 ppm), 3-methylbenzyl alcohol (3-MBA) (50, 100 ppm), or m-ALD (50, 100 ppm). A single 6-h inhalation exposure of rats to m-XYL inhibited pulmonary CYPs 2B1, 2E1, and 4B1 in a dose-dependent manner. Inhalation of 3-MBA inhibited pulmonary CYPs 2B1 and 4B1 in a dose-dependent manner. m-ALD inhibited pulmonary CYPs 2B1 and 2E1 in a dose-dependent manner, while 4B1 activity was increased dose dependently. Nasal mucosa CYP 2B1 and 2E1 activity was inhibited following exposure to m-XYL dose dependently, 3-MBA inhibited nasal mucosa CYPs 2E1 and 4B1 dose dependently. CYPs 2B1, 2E1, and 4B1 were inhibited in a dose-dependent fashion following inhalation of m-ALD. Following high-performance liquid chromatography (HPLC) analysis, m-ALD was detected after in vivo exposure to m-XYL, m-ALD, and 3-MBA in a dose-dependent manner, with highest m-ALD levels in the nasal mucosa and lung. Alteration of cytochrome P-450 activity by m-XYL could result in increased or decreased toxicity, changing the metabolic profiles of xenobiotics in coexposure scenarios in an organ-specific manner.