Toxicological assessment of kretek cigarettes Part 6: the impact of ingredients added to kretek cigarettes on smoke chemistry and in vitro toxicity.

Mainstream smoke (MS) from experimental kretek cigarettes with three ingredient mixes at low (typical use level) and high (2.5 or 3 times that level) inclusion rates was compared to a control kretek cigarette of identical construction (cloves and humectants), but without the addition of ingredients. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes were assessed. The MS composition of the kretek cigarettes was characterized by a comprehensive set of analytes (55 smoke constituents). Furthermore, the smoke was assessed in vitro for its cytotoxicity in the Neutral Red Uptake assay (particle phase and gas/vapor phase separately) in mouse embryo BALB/c 3T3 cells, and for mutagenicity/genotoxicity in the Salmonella typhimurium reverse mutation assay and the mammalian cell mouse lymphoma TK assay in L5178Y cells, the latter with and without metabolic activation. There were some statistically significant differences in the yield of smoke constituents (increases as well as decreases, nearly all of them less than ± 20%) as a result of the addition of the ingredient mixes. However, the addition of the three different mixes of ingredients to the experimental kreteks did not change the in vitro cytotoxicity and mutagenicity/genotoxicity of the smoke, when compared to the control kretek cigarette.

Toxicological assessment of kretek cigarettes: Part 2: kretek and American-blended cigarettes, smoke chemistry and in vitro toxicity.

Two commercial kretek cigarettes typical for the Indonesian market and a reference kretek cigarette were compared to the American-blended reference cigarette 2R4F by smoke chemistry characterization and in vitro cytotoxicity and mutagenicity assessments. Despite the widely diverse designs and deliveries of the selected kretek cigarettes, their smoke composition and in vitro toxicity data present a consistent pattern when data were normalized to total particulate matter (TPM) deliveries. This confirms the applicability of the studies' conclusions to a wide range of kretek cigarette products. After normalization to TPM delivery, nicotine smoke yields of kretek cigarettes were 29-46% lower than that of the 2R4F. The yields of other nitrogenous compounds were also much lower, less than would be expected from the mere substitution of one third of the tobacco filler by clove material. Yields of light molecular weight pyrolytic compounds, notably aldehydes and hydrocarbons, were reduced, while yields of polycyclic aromatic hydrocarbons were unchanged and phenol yield was increased. The normalized in vitro toxicity was lowered accordingly, reflecting the yield reductions in gas-phase cytotoxic compounds and some particulate-phase mutagenic compounds. These results do not support a higher toxicity of the smoke of kretek cigarettes compared to American-blended cigarettes.