RESUMEN
Toxicological comparisons were made of three commercial cigarettes, namely Marlboro full flavor, Marlboro Lights, and Marlboro Ultra Lights, with the 1R4F reference cigarette. The main comparison was a 90-d inhalation study with mainstream smoke at 150 mg total particulate matter per cubic meter, in Sprague-Dawley rats using 6 h/d and 7 d/w exposures. The principal endpoint was histopathology of the respiratory tract, along with examinations of free lung cell counts after broncho-alveolar lavage. Additional studies on mainstream smoke included Salmonella mutagenicity, cytotoxicity of particulate and gas/vapor phases, and analytical chemistry. The exposures produced effectively the same responses in each of the four groups, and the histopathology results in the commercial cigarette groups were also effectively the same. The 1R4F was also tested at 75 and 200 mg/m(3), and most of the histopathology results obtained here showed dose-response relationships. The free lung cell responses were similar in the 1R4F/commercial cigarette comparison, and there were dose-related changes in the 1R4F groups, most notably for neutrophils. Most of the changes produced in the 90-d of exposure were resolved in a 42-d post-inhalation period. Responses in the in vitro and analytical assays for the four cigarettes were in general similar, when data were expressed either per mg TPM or per mg tar yield. There were judged to be no toxicologically meaningful differences between the profiles evaluated at similar smoke concentrations for the three commercial cigarettes and for the 1R4F using these assays.
Asunto(s)
Nicotiana/toxicidad , Sistema Respiratorio/efectos de los fármacos , Salmonella/efectos de los fármacos , Humo/efectos adversos , Animales , Células 3T3 BALB , Líquido del Lavado Bronquioalveolar/citología , Carboxihemoglobina/análisis , Supervivencia Celular/efectos de los fármacos , Femenino , Masculino , Ratones , Mutágenos/toxicidad , Material Particulado/análisis , Material Particulado/toxicidad , Ratas , Ratas Sprague-Dawley , Pruebas de Función Respiratoria , Sistema Respiratorio/patología , Salmonella/genética , Humo/análisisRESUMEN
This study has examined the possible effects of ammonia-forming ingredients added to tobacco and of ammonia in mainstream (MS) smoke on the nicotine transfer from tobacco to smoke. The U.S. 1998 Marlboro Lights King Size cigarette was used as a control for four test variants that differed from the control as follows: first, a reduction in ammonia-forming ingredients added to the reconstituted tobaccos; second, no ammonia-forming ingredients added to the reconstituted tobaccos; third, no ingredients at all added to the reconstituted tobaccos; and fourth, no ingredients at all added to the entire tobacco blend. Data were obtained on nicotine in tobacco, tar and nicotine and ammonia in MS smoke, soluble ammonia in the cigarette tobacco, "tobacco pH," and "smoke pH" using the FTC machine-smoking paradigm. Previous research on these cigarettes demonstrated that >99% of the MS smoke nicotine was captured and quantified by the FTC method. Statistically significant increases in soluble ammonia and MS smoke ammonia were observed for those cigarettes with ammonia-forming ingredients added to the reconstituted tobacco. However, ingredients, including ammonia and ammonia-forming compounds added to the tobacco or ammonia in the mainstream smoke in the Marlboro Lights King Size cigarette, did not increase the relative nicotine transfer or the "pH of aqueous extracts of MS smoke." "Tobacco pH" and "smoke pH" had no scientific or practical value for the cigarettes in this study.