Measures of dependence in menthol and nonmenthol smokers - A comprehensive narrative review.

Introduction. More than a decade ago, concerns were raised that menthol in cigarettes might enhance addiction to smoking. This article provides a comprehensive review of published studies examining cigarette dependence among menthol and nonmenthol smokers. The purpose of the review is to evaluate the scientific evidence to determine if menthol increases cigarette dependence. Materials and Methods. The published literature was searched in 2019 for studies that provide evidence on cigarette dependence among menthol compared to nonmenthol smokers. Included in this review are published studies that compare menthol and nonmenthol smokers based on widely accepted and validated measures of dependence, or other established predictors of dependence (age of smoking initiation [first cigarette]/age of progression [regular/daily smoking]) and indicators of dependence (smoking frequency, cigarettes smoked per day, time to first cigarette after waking, night waking to smoke, smoking duration). Results and Conclusion. Based on a review of the available studies, including those with adjusted results and large representative samples, reliable and consistent empirical evidence supports a conclusion that menthol smokers are not more dependent than nonmenthol smokers and thus menthol in cigarettes does not increase dependence.

A review and assessment of menthol employed as a cigarette flavoring ingredient.

Cigarette smoking is established as a substantial contributor to risks for cancer, cardiovascular and respiratory diseases. Less is known about the potential of cigarette composition to affect smoking risks. The use of cigarette flavoring ingredients such as menthol is currently of worldwide public health and regulatory interest. The unique conditions of menthol inhalation exposure that occur coincident with that of the complex cigarette smoke aerosol require specialized studies to support an assessment of its safety in cigarette flavoring applications. The present state of knowledge is sufficient to support an assessment of the safety of the use of menthol in cigarettes. Scientific, smoking behavioral and epidemiological data available through mid-2009 is critically reviewed and a broad convergence of findings supports a judgment that menthol employed as a cigarette tobacco flavoring ingredient does not meaningfully affect the inherent toxicity of cigarette smoke or the human risks that attend smoking. There remains a need for well-designed studies of the potential of menthol to affect smoking initiation, cessation and addiction in order to differentiate any independent effects of menthol in cigarettes from those imposed by socioeconomic, environmental and peer influences on these complex human behaviors.

Smokers of menthol and nonmenthol cigarettes exhibit similar levels of biomarkers of smoke exposure.

There has been speculation that the addition of menthol to cigarettes may affect the manner in which cigarettes are smoked, potentially influencing smokers' exposures to smoke constituents that have been associated with smoking-related diseases. One hundred twelve male and female smokers participated in a parallel-arm study to determine whether the ad libitum smoking of menthol cigarettes results in differences in smoke constituent exposure biomarkers in blood and urine relative to those smoking nonmenthol cigarettes having similar machine-measured (Federal Trade Commission) yields of approximately 9 to 10 mg "tar." The study subjects were provided cigarettes of their preferred menthol or nonmenthol types prior to two 24-hour study intervals spaced one week apart. Carboxyhemoglobin levels were measured in blood samples drawn at midafternoon following the two 24-hour urine collection periods. Six urinary nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine and respective glucuronides) were determined as measures of nicotine intake, and urinary 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide were determined to assess exposure to the tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridinyl)-1-butanone. Subjects' median blood carboxyhemoglobin values did not differ significantly between the cigarette types. Neither total urinary NNAL nor urinary nicotine equivalents exhibited statistically significant differences between the menthol and nonmenthol cigarette smokers. The present findings indicate that moderately heavy smokers of menthol and nonmenthol cigarettes of similar machine-generated smoke yield exhibit essentially identical levels of biomarkers of smoke constituent exposure. These results are consistent with the substantial majority of epidemiology studies to date that suggest the risks attending the smoking of menthol and nonmenthol cigarettes are similar.

Toxicologic evaluation of humectants added to cigarette tobacco: 13-week smoke inhalation study of glycerin and propylene glycol in Fischer 344 rats.

Glycerin (CAS no. 56-81-5) and propylene glycol (CAS no. 57-55-6) are commonly used as humectant ingredients in manufactured cigarettes to control and maintain the moisture content of the cut tobacco filler. The potential of these added humectants to affect the toxicity of cigarette smoke was investigated in a subchronic nose-only smoke inhalation study in rats. Filtered test cigarettes were prepared from an American-style tobacco blend containing either glycerin added at 5.1% w/w tobacco, propylene glycol at 2.2% w/w tobacco, or combinations of these humectants totaling 2.3%, 3.9%, and 7.2% w/w tobacco. Other groups of animals were exposed similarly to the smoke of reference cigarettes without added humectants, or to filtered air (sham control). Smoke exposures were conducted for 1 h/day, 5 days/wk for 13 wk, at target smoke particulate concentrations of 350 mg/m(3). All smoke-exposed groups had equivalent increases in blood carboxyhemoglobin, serum nicotine, and serum cotinine relative to the air controls. Smoke-associated reductions in body weights and occasional increases in heart and lung weights were generally similar among the various exposure conditions at necropsy. Increases in serum alkaline phosphatase and decreases in serum glucose and cholesterol were observed among smoke-exposed females relative to air controls. However, no significant differences in these parameters were evident between the humectant-containing and reference cigarette smoke exposure groups. Assessments of respiration conducted after 3, 6, 9, and 12 wk of smoke exposure indicated an initial smoke-related but not humectant-related decrease in respiratory rate, tidal volume, and minute volume during the first 20 min of each smoke exposure. Respiratory-tract histopathology was consistent across sexes and smoke groups, comprising (1) diffuse and focal alveolar pigmented macrophages and chronic interstitial inflammation in the lung, (2) laryngeal epithelial hyperplasia, squamous metaplasia, and scab formation, and (3) epithelial hyperplasia in the anterior nose. Smoke-related histopathology resolved substantially during a 6-wk postexposure recovery period. Addition of the tested humectants to cigarettes, singly or in combination, had no meaningful effect on the site, occurrence, or severity of respiratory-tract changes or on the measured indices of pulmonary function. It was concluded that the addition of glycerin and propylene glycol to cigarettes does not significantly affect the biological activity of inhaled cigarette smoke in this rat model.