Toxicological evaluation of smokeless tobacco: 2-year chronic toxicity and carcinogenicity feeding study in Wistar Han rats.

Unlabelled: A comprehensive 2-year oral chronic toxicity/carcinogenicity study was conducted with smokeless tobacco using modern toxicological test methods and well-accepted standards. The study included a 1-year interim subgroup to assess toxicity at that intermediate time point. Test groups consisted of a tobacco blend (B) used in snus, and an aqueous tobacco extract of that tobacco blend (E) administered at 0.

Toxicological evaluation of smokeless tobacco: 90-day rodent feeding studies.

This manuscript presents data from 90-day toxicology studies designed to characterize the subchronic effects of a smokeless tobacco blend and an aqueous extract of that blend when administered to rodents in NTP-2000 feed. Positive control (nicotine tartrate) and treatment groups were matched for a range of nicotine levels. The doses evaluated were 0.

A Bayesian statistical analysis of mouse dermal tumor promotion assay data for evaluating cigarette smoke condensate.

The mouse dermal assay has long been used to assess the dermal tumorigenicity of cigarette smoke condensate (CSC). This mouse skin model has been developed for use in carcinogenicity testing utilizing the SENCAR mouse as the standard strain. Though the model has limitations, it remains as the most relevant method available to study the dermal tumor promoting potential of mainstream cigarette smoke.

Upper airways sensory irritation responses of mice exposed to mainstream smoke from four cigarette types.

Relative sensory irritation responses for Swiss-Webster mice exposed nose-only to mainstream tobacco smoke were evaluated for several cigarette types using a smoking regimen consisting of a 35-ml puff, 2 s in duration, taken once per minute. The degree of sensory irritation for each cigarette type was evaluated as the smoke concentration inducing a 50% reduction in breathing frequency. The smoke concentration inducing 50% respiratory depression is called the RD(50) value.

A summary of toxicological and chemical data relevant to the evaluation of cast sheet tobacco.

A tiered testing strategy based on a comparative chemical and biological testing program has been developed to evaluate the potential of tobacco processes, ingredients, or other technological developments to change the biological activity that results from burning tobacco. Cast sheet tobacco is a specific type of reconstituted tobacco sheet that can be used in the manufacture of cigarettes. The comparative chemical and biological testing program was used to compare the mainstream smoke and cigarette smoke condensate (CSC) from a Reference cigarette that did not contain cast sheet to that collected from Test cigarettes containing cast sheet at a final blend level of either 10% or 15%.

Comparative 13-week inhalation study of cigarette smoke from cigarettes containing cast sheet tobacco.

A subchronic, nose-only inhalation study was conducted to compare the effects of mainstream smoke from a reference cigarette containing conventional reconstituted tobacco sheet at 30% of the finished blend to mainstream smoke from cigarettes containing 10% or 15% cast sheet (a specific type of reconstituted tobacco sheet) substituted for part of the conventional reconstituted tobacco. Male and female Sprague-Dawley rats were exposed for 1 h/day, 5 d/wk, for 13 wk to mainstream smoke at 0, 0.06, 0.

Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells.

The current study tested the hypothesis that the pulmonary carcinogenic potential of cadmium (Cd) is related to its ability to inhibit the expression (mRNA and protein) and activity of 8-oxoguanine-DNA glycosylase (OGG1), a base excision repair (BER) enzyme that functions to preferentially excise pre-mutagenic 7,8-dihydro-8-oxoguanine (8-oxoG) from DNA. We demonstrate that a single Cd aerosol exposure of adult male Lewis rats causes time- and dose-dependent down-regulation in the pulmonary levels of rOGG1 mRNA and OGG1 protein, quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays and western analyses, respectively. Immunohistochemical studies confirmed that Cd inhalation reduces the relative amount of OGG1 in lungs of exposed animals without altering its over-all distribution within the lung, which appears to be more prominent within the alveolar epithelium.