ABSTRACT: INTRODUCTION:The World Health Organization (WHO) Framework Convention on Tobacco control recognizes the need for tobacco product regulation. In line with that, the WHO Study Group on Tobacco Product Regulation (TobReg) proposed to regulate nine toxicants in mainstream cigarette smoke, including aldehydes, volatile organic compounds (VOCs), and carbon monoxide (CO). We analyzed their relations in 50 commercially available cigarette brands, using two different smoking regimes, and their dependence on sugar and humectant concentrations in tobacco filler. METHODS:We measured sugar and humectant in tobacco filler and aldehydes, VOCs, and tar, nicotine, and CO (TNCO) in mainstream smoke. The general statistics, correlations between emission yields, and correlations between contents and emissions yields were determined for these data. RESULTS:For aldehydes, several significant correlations were found with precursor ingredients in unburnt tobacco when smoked with the Intense regime, most prominently for formaldehyde with sucrose, glucose, total sugars, and glycerol. For VOCs, 2,5-dimethylfuran significantly correlates with several sugars under both International Standards Organization (ISO) and Intense smoking conditions. A correlation network visualization shows connectivity between a sugar cluster, an ISO cluster, and an Intense cluster, with Intense formaldehyde as a central highest connected hub. CONCLUSIONS:Our multivariate analysis showed several strong connections between the compounds determined. The toxicants proposed by WHO, in particular, formaldehyde, can be used to monitor yields of other toxicants under Intense conditions. Emissions of formaldehyde, acetaldehyde, acrolein, and 2,5-dimethylfuran may decrease when sugar and humectants contents are lowered in tobacco filler. IMPLICATIONS:Our findings suggest that the aldehydes and VOCs proposed by TobReg are a representative selection for smoke component market monitoring purposes. In particular, formaldehyde yields may be useful to monitor emissions of other toxicants under Intense conditions. Since the most and strongest correlations were observed with the Intense regime, policymakers are advised to prescribe this regime for regulatory purposes. Policymakers should also consider sugars and humectants contents as targets for future tobacco product regulations, with the additional advantage that consumer acceptance of cigarette smoke is proportional to their concentrations in the tobacco blend.