Evaluation of the potential effects of ingredients added to cigarettes. Part 1: cigarette design, testing approach, and review of results.

A testing program was designed to evaluate the potential effects of 333 ingredients added to typical commercial blended test cigarettes on selected biological and chemical endpoints. Ingredients were incorporated into the test cigarettes as they are normally used in the manufacturing process. The studies performed included a bacterial mutagenicity screen (Ames assay), a mammalian cell cytotoxicity assay (neutral red uptake), determination of smoke chemical constituents, and a 90-day nose-only smoke inhalation study in rats. Three pairs of test cigarettes were produced, each containing one of three different groups of ingredients. In each pair, one of the cigarettes contained the normal approximate use level of the ingredients (low-level) and the other a 1.5-3 multiple of the normal use level (high-level). Analysis of the test cigarettes for selected ingredients or markers indicated that the target application rates were achieved and that the cigarettes had been manufactured as intended. Evaluation of cigarette performance indicated that the addition of the ingredients at high levels did not significantly alter the burning characteristics of the test cigarettes. Specific details of the individual studies conducted as part of an ingredient evaluation program are discussed in Parts 2-4 of this publication series (Food and Chemical Toxicology, 2002, 40, 93-104; Food and Chemical Toxicology, 2002, 40, 105-111; Food and Chemical Toxicology, 2002, 40, 113-131). The results of the smoke chemistry studies indicated a reduction in the majority of the smoke constituents and a few isolated instances of increases when compared to the control cigarettes. These smoke chemistry changes, while statistically significant, were not supported by any significant alteration in the biological effects of cigarette smoke normally seen with the bacterial mutagenicity assay, cytotoxicity assay or subchronic inhalation study. Based on the results of these studies, it can be concluded that these ingredients added to tobacco do not add significantly to the overall toxicity of cigarettes.