Among more than 6000 constituents (Rodgman and Perfetti, 2013), several harmful and potentially harmful constituents (HPHCs) have been associated with the causation of disease in smokers, such as aromatic amines (Bartsch et al., 1993; Vineis and Pirastu, 1997), gas-phase constituents (Costa et al., 1986; Penn and Snyder, 1996; Witschi et al., 1997), oxygen-free radicals (Pryor, 1997; Valavanidis et al., 2009), polycyclic aromatic hydrocarbons (PAHs) (Penn et al., 1981; Smith et al., 2000), and tobacco-specific N-nitrosamines (TSNAs) (Hecht, 1998, 1999). However, a causal link between a specific smoke constituent and disease has not been conclusively established.
Since it is not possible to quantify all constituents present in cigarette smoke, various priority lists of smoke toxicants in mainstream cigarette smoke have been proposed for the evaluation of commercial market cigarettes based mainly on risk assessments (Cunningham et al., 2011; Fowles and Dybing, 2003; Haussmann, 2012; Hecht, 2006; Hoffmann et al., 1997; Pankow et al., 2007; Rodgman and Green, 2003; Smith and Hansch, 2000; Talhout et al., 2011; Vorhees and Dodson, 1999; Xie et al., 2012).
Smoke constituent reporting
Smoke constituent reporting and brand-by-brand disclosure is required by different regulatory authorities, either on an annual basis (Health Canada, British Columbia, Brazil, and Taiwan) or as a one-off disclosure (Massachusetts Department of Health, UK, and Australia) (Wright, 2015). The lists of smoke constituents to be reported show a great deal of similarity between different regulatory authorities (Table 1); however, with the exception of Health Canada (Health Canada, 2000), specific test methods have not been defined or validated.
Philip Morris International’s aerosol chemistry list of 58 constituents
The list of constituents measured in the evaluation of the mainstream aerosol composition of PMI's Tobacco Heating System (THS) is presented in Table 1 and compared to lists of priority smoke constituents proposed by the WHO Study Group on Tobacco Product Regulation (TobReg) (WHO, 2007; WHO, 2008; WHO, 2015), Health Canada (Health Canada, 2000), and the FDA (U.S. FDA, 2012a and b). The list of 58 constituents (‘PMI-58 list’) covers smoke constituents determined by the International Organization for Standardization (ISO) standard methods (carbon monoxide [CO], nicotine, nicotine-free dry particulate mattter [NFDPM], total particulate matter [TPM], and water) and chemical constituent representatives of all major toxicologically relevant chemical classes of compounds present in both the particulate phase and gas/vapor phase of cigarette smoke and was originally based on recommendations by the U.S. Consumer Product Safety Commission on smoke constituents presenting toxicological concerns in low ignition-potential cigarettes (US CPSC, 1993) and compounds reported in cigarette smoke which have been classified as either known or probable human carcinogens by the International Agency for Research on Cancer (IARC, 1985). Further additional HPHCs identified in mainstream cigarette smoke were considered and, if deemed relevant, included in the PMI-58 list of constituents requiring measurement for product evaluation. The PMI-58 list contains all constituents required for reporting by different regulatory authorities including the HPHCs which are subject to reporting on the FDA’s abbreviated list (U.S. FDA, 2012b), Health Canada (Health Canada, 2000), and all smoke constituents identified as priority toxicants and proposed for reporting by TobReg (WHO, 2007; WHO 2008; WHO, 2015).
Collection of aerosol for HPHC measurements
All machine-smoking methods have their limitations (Borgerding and Klus, 2005; Dixon and Borgerding, 2006; Roemer and Carchman, 2011), particularly the inability to reflect the variation in human puffing patterns and exposure to smoke constituents (Hammond et al., 2007; Stratton et al., 2001). Compared to the ISO 3308 machine-smoking regimen (ISO, 1991), the more intense machine-smoking regimen proposed by Health Canada (2000) results in much higher aerosol constituent yields which are thought to more closely represent smoker exposure to smoke constituents (Hammond et al., 2007; Hammond and O’Connor, 2008). No single machine-smoking regimen can represent all human smoking behavior (Stratton et al., 2001); however, machine-smoking testing is useful for characterizing tobacco product emissions for design and regulatory purposes. Data on emissions from machine measurements may also be useful as inputs for product hazard assessment, but smoking machine-derived data are not intended to be, nor are they valid as, measures of human exposure or risks (Hatsukami et al., 2012; WHO, 2012).