Effects of Flavoring and Casing Ingredients on the Toxicity of Mainstream Cigarette Smoke in Rats

Abstract

A series of in vitro and in vivo studies evaluated the potential effects of tobacco flavoring and casing ingredients. Study 1 utilized as a reference control cigarette a typical commercial tobacco blend without flavoring ingredients, and a test cigarette containing a mixture of 165 low-use flavoring ingredients. Study 2 utilized the same reference control cigarette as used in study 1 and a test cigarette containing eight high-use ingredients. The in vitro Ames Salmonella typhimurium assay did not show any increase in mutagenicity of smoke condensate from test cigarettes designed for studies 1 and 2 as compared to the reference. Sprague-Dawley rats were exposed by nose-only inhalation for 1 h/day, 5 days/wk for 13 wk to smoke from the test or reference cigarettes already described, or to air only, and necropsied after 13 wk of exposure or following 13 wk of recovery from smoke exposure. Exposure to smoke from reference or test cigarettes in both studies induced increases in blood carboxyhemoglobin ((COHb)) and plasma nicotine, decreases in minute volume, differences in body or organ weights compared to air controls, and a concentration-related hyperplasia, squamous metaplasia, and inflammation in the respiratory tract. All these effects were greatly decreased or absent following the recovery period. Comparison of rats exposed to similar concentrations of test and reference cigarette smoke indicated no difference at any concentration. In summary, the results did not indicate any consistent differences in toxicologic effects between smoke from cigarettes containing the flavoring or casing ingredients and reference cigarettes.

Toxicological assessment of kretek cigarettes part 4: Mechanistic investigations, smoke chemistry and in vitro toxicity

“…This is in accordance with the literature. Several authors studying the addition of the same ingredients to control cigarettes made from different blends have reached the same conclusion Renne et al, 2006;Rustemeier et al, 2002).…”

O impacto dos aditivos do tabaco na toxicidade da fumaça do cigarro: uma avaliação crítica dos estudos patrocinados pela indústria do fumo

“…Nr-COH; neutral red uptake cytoxicity assay with COH cells; SCE-COH: sister chromatid exchange assay in Chinese hamster ovary cells. Table 2 shows that the impact of tobacco additives on cigarette mainstream smoke toxicity was investigated through in vitro mutagenicity (Ames test) and mammalian cytotoxicity (Neutral red uptake) assays 29,30,31 , and in vivo sub-chronic (90 day) inhalation toxicity studies with rats 31,32,33,34 . In addition to these investigations (Table 2), a sub-chronic toxicity (26-week) study tested smoke condensates from cigarettes with and without tobacco additives for tumor promoting activity in the two-stage carcinogenicity test on mouse back skin 35 .…”

“…The Salmonella assays, on the other hand, were generally conducted both in the presence and in the absence of extrinsic metabolic activation systems (i.e. Aroclor 1254-induced rat liver post-mitochondrial fraction) 29,31 . In the mammalian cytoxicity assay, both the total particulate matter and the water-soluble portion of the gas/vapor phase (GVP) trapped in PBS were administered to cells (EC50s for GVP were comparable to those obtained for total particulate matter) 29 .…”

“…In the mammalian cytoxicity assay, both the total particulate matter and the water-soluble portion of the gas/vapor phase (GVP) trapped in PBS were administered to cells (EC50s for GVP were comparable to those obtained for total particulate matter) 29 . Salmonella mutagenicity assays, however, tested total particulate matter but not GVP yielded by test and control cigarettes 29,31 .…”

Influence of Additives on Cigarette Related Health Risks

“…• RENNE et al (240) RENNE et al (240) (250). The additives were tested individually using different amounts added to experimental cigarettes.…”