U.S. FDA's list of HPHCs

    Comparison between HPHC levels in THS 2.2 aerosol and cigarette smoke

    17 March 2023

    In 2012, the U.S. Food and Drug Administration (FDA) published a list of harmful and potentially harmful constituents (HPHCs) found in tobacco products and tobacco smoke, known as the FDA 93 list as it comprises 93 compounds or classes of compounds. This list covers toxicants linked to diseases such as cancer and cardiovascular disease, among others. 

    Also in 2012, the FDA published a guidance document for the tobacco industry for the reporting of HPHCs in tobacco smoke, which included 18 analytes to serve as a representative sample from among the FDA 93 list. These 18 analytes focus on smoke constituents for which testing and analytic methods are well established and widely available, and it included representatives of several different chemical classes. In our PMI-58 list of analytes, we include all 18 of those analytes in addition to recommended analytes from lists published by the World Health Organization and Health Canada.  

    Below, we’ve listed the levels of those HPHCs (with the exception of nicotine) measured in the smoke of a standard reference cigarette (3R4F) and the aerosols of two versions of our Tobacco Heating System (THS 2.2), the THS 2.2 Regular and the THS 2.2 Smooth Menthol. In all cases where a comparison could be made, we found that HPHC levels in the THS were lower compared to 3R4F, with an average reduction of more than 90.5% on a stick basis for THS 2.2 Regular and more than 91.0% on a stick basis for THS 2.2 Smooth Menthol.

    The reductions in this table are fully in line with the one previously calculated using the PMI-58 list. The similarity of the results between the THS regular and THS menthol also show that the reduction in levels of HPHCs is related to the heat-not-burn principle and not impacted by the nature of the flavor system.

    Here are the levels of HPHCs, as well as standard deviation (SD), for the THS 2.2 Regular and THS 2.2 Smooth Menthol, compared to 3R4F. The number of replicates for each analyte is 3. All analyses were conducted by Labstat International ULC (Kitchener, ON, Canada), an independent laboratory, according to their own methods and protocols. The standard Health Canada Intense smoking regime was applied to both the 3R4F and the THS.

    Abbreviations:

    • AαC: 2-Amino-9H-pyrido[2,3-b]indole
    • CDD: Chlorodibenzo-p-dioxin
    • CDF: Chlorodibenzofuran
    • CO: Carbon monoxide
    • Glu-P-1: 2-Amino-6-methyldipyrido[1,2-a: 3',2'-d]imidazole
    • Glu-P-2: 2-Aminodipyrido[1,2-a: 3',2'-d]imidazole
    • IQ: 2-Amino-3-methylimidazo[4,5-f]quinoline
    • MeAαC: 2-Amino-3-methyl)-9H-pyrido[2,3-b]indole
    • NDEA: N-Nitrosodiethylamine
    • NDELA : N-Nitrosodiethanolamine
    • NDMA: N-Nitrosodimethylamine
    • NEMA: N-Nitrosomethylethylamine
    • NMOR: N-Nitrosomorpholine
    • NPIP: N-Nitrosopiperidine
    • NPYR: N-Nitrosopyrrolidine
    • PAHs: Polycyclic aromatic hydrocarbons
    • PhIP: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
    • Trp-P-1: 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole
    • Trp-P-2: 1-Methyl-3-amino-5H-pyrido[4,3-b]indole
    • TSNA: Tobacco-specific nitrosamines
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