Effect of a flue-curing process that reduces tobacco specific nitrosamines on the tumor promotion in SENCAR mice by cigarette smoke condensate.

A 30-week dermal tumor promotion study was conducted to evaluate the dermal tumor-promoting potential of cigarette smoke condensate (CSC) collected from cigarettes containing flue-cured tobacco cured by a heat-exchange process (HE) relative to that of cigarettes containing flue-cured tobacco cured by the traditional direct-fire process (DF). Heat-exchange process cured tobacco contains significantly lower concentrations of tobacco specific nitrosamines (TSNAs) compared to traditional direct-fire cured tobacco. Mainstream CSCs were collected by cold trap from smoke generators using the Federal Trade Commission puffing regimen. Groups of 40 female SENCAR mice were initiated by a single application of 75 micro g 7,12-dimethylbenz[a]anthracene (DMBA) to the shaved dorsal skin. CSCs were then applied to the skin three times/week for 29 weeks at 9, 18, or 36mg tar/application. End-points included body weights, clinical observations, organ weights, dermal tumor development and histopathology. The numbers of dermal tumors and the numbers of tumor-bearing mice for each CSC were statistically different from the DMBA/acetone control group and increased with increasing dose. When corresponding doses of each CSC were compared, only the DMBA/mid-dose HE CSC group was statistically significantly different (lower) from the corresponding DMBA/mid-dose DF CSC group. In this assay, the dermal tumor-promotion potential of CSC from heat-exchange flue-cured tobacco did not differ from that of traditional direct-fire flue-cured tobacco CSC.

Comparative studies of DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or primarily heat tobacco.

A new cigarette (Eclipse) that primarily heats rather than burns tobacco has been developed. Since Eclipse primarily heats tobacco, the smoke chemistry is much simplified, consisting of 80% glycerol and water. With the simplified smoke chemistry, it would be expected that toxicological activity would be reduced. Smoke and smoke condensate from Eclipse have consistently yielded markedly reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke and smoke condensate from the 1R4F Kentucky reference cigarette, which is representative of typical low 'tar' cigarettes sold in the U.S. today. The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin tissue of dermally-exposed mice and to compare the results with those obtained with CSC from the 1R4F Kentucky reference cigarette. CSC from Eclipse or 1R4F cigarettes was applied dermally to SENCAR mice three times a week for 30 weeks. Amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per week. Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method with P1 nuclease modification. Distinct time and dose-dependent diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with 1R4F CSC. The relative adduct labeling (RAL) values of lung, heart and skin DNA from reference CSC-treated animals were significantly greater (p<0.05) than those of the solvent control animals. No corresponding DRZs were observed at any dose from the DNA of animals treated with CSC from Eclipse or solvent control (acetone) and the RAL values observed following application of Eclipse were not increased relative to the solvent control. These results provide additional evidence that the smoke condensate from the Eclipse cigarette is markedly less genotoxic than smoke condensate from tobacco-burning cigarettes representative of those currently sold in the U.S.

Dermal oncogenicity bioassays of acrylic acid, ethyl acrylate, and butyl acrylate.

Male C3H/HeJ mice (40 per group) were treated with 25-microliter applications of undiluted ethyl acrylate, 1% acrylic acid, or 1% butyl acrylate on the dorsal skin 3 times weekly for their lifetime. A negative control group received acetone (diluent) only, and a positive control group received 0.1% 3-methylcholanthrene (MC). No epidermal tumors were observed in the animals that received any of the three test substances. In the positive control group, 39 animals had skin tumors, including 33 with confirmed squamous-cell carcinomas. Nonneoplastic skin changes such as dermatitis, dermal fibrosis, epidermal necrosis, and hyperkeratosis were observed in several mice that received ethyl acrylate. No statistically significant effects on survival were seen. Therefore, there was no evidence for local carcinogenic activity of acrylic acid, ethyl acrylate, or butyl acrylate under the conditions of these studies.