| Product use behavior |
| 1 | Daily product consumption | The number or amount of consumables used per day |
Consumption per day (cigarettes/day (CPD), sticks/day, portions/day, pouches/day, and so on) can be assessed by interview, questionnaire, or diaries or counted the number of used consumables. Amount per day (mL/day, mg/day) can be calculated by measuring or weighting the consumables (e.g., e-liquid) before and after using.
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20 CPD 5 to 25 mL of e-liquid /day with regard e-vaper products, weekly consumption of e-liquid (mL/week) and number of puffs/day has been also assessed (96) 1 to 5 pouches/day with regard oral products, weekly consumption of cans has been also assessed (97)
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| 2 | Pack years (PY) | The number of packs smoked in a day multiplied by the number of years spent smoking |
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20 PY (one pack per day × 20 years / 2 packs per day × 10 years [based on a pack of 20 cigarettes]) used as a crude surrogate for lifetime exposure without allowing for constituent yield and smoking behavior, often used in epidemiological studies (98) although this has been criticized (99) Brinkman index (BI; number of cigarettes smoked in a day multiplied by the number of years spent smoking) has also used as a crude surrogate for lifetime exposure (100,101)
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| 3 | Exposure dose | The exposure dose is the amount of a specified constituent present in the external medium (such as air, water, tobacco smoke, aerosol, extraction, food) that is deposited or absorbed in the body of an exposed individual over a specific duration. |
Mass (mg, μg, ng, pg) per time (day and so on)
estimated the amount of constituent that may reach or is at the portal of entry to the body;
assessed by measuring biomarkers of exposure in body fluids or organs (biological monitoring).
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MLE of nicotine (mg/cig or mg/day) external exposure (intake) dose is the amount of constituent that may reach or is at the portal of entry to the body See ‘Mouth level exposure (MLE) / Yield in-use (YIU) / Intake’ Urinary nicotine equivalents (mg/24 h) internal exposure (uptake) dose is the amount of constituent that that is measured as a concentration in body fluids, excreta, or tissues See ‘Biomarker of exposure (BOE)’
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| 4 | Puffing topography / Puffing pattern | The profile of puff characteristics including puff frequency, duration, volume, interval, and regularity of these parameters for an inhalable TNP |
A complex set of measurements including puff number, puff duration, puff volume, puff interval and so on. Puffing topography is assessed by specialized instruments with pressure and flow measurement capabilities.
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Puff pattern is fixed, with regular puff intervals in standard machine smoking/vaping regimes
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ISO 3308:2012 (a 35 ml puff volume, a 2-s puff duration, a 60-s puff interval [35/2/60] as standard regime for combustible cigarettes) (102)
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ISO 20778:2018 (a 55 ml puff volume, a 2-s puff duration, a 30-s puff interval with 100% vent blocking [55/2/30] as an intense regimen for combustible cigarette, 55/2/30 without vent blocking as a standard regime for electrically HTP and carbon HTP) (2,1,104)
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ISO 20768:2018 (a 55 ml puff volume, a 2-s puff duration, a 30-s puff interval [55/3/30] as a standard regime for e-vapor products and aerosol HTP) (2,15)
(see Figure 1) |
| 13 | Puff flow rate / Flow rate | The volumetric flow rate of puff from an inhalable TNP |
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17.5, 18.3, or 27.5 mL/s under standard machine smoking/vaping regimes (108) Average and peak flow rate (calculated mean and maximum volumetric flow rate for each puff or across all puffs from an inhalable TNP) can be calculated by puffing topography instrument
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| 14 | Draw pressure / Puff pressure / Puff draw pressure | The mouth-end pressure (vacuum) recorded per individual puff from an inhalable TNP |
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| 15 | Draw resistance | The ratio of draw pressure to puff flow rate per individual puff from an inhalable TNP |
Pressure (mm Water Gauge [mmWG], mm H2O, Pascals [Pa]) per flow (mL/s) calculated from measurements made with a puffing topography instrument.
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| 16 | Duration of product use / Total session length | The total time elapsed from the start of the first puff to the end of the last puff of an inhalable TNP |
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165–420 s/cig calculated from (105) 330 or 390 s/HTP stick, 1470 s/e-vapor product calculated from (107)
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| 17 | Total puff duration | The cumulative time for all puffs from an inhalable TNP |
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11.6–22.6 s/cig calculated from (105) 24 or 28 s/HTP stick, 150 s/e-vapor product calculated from (107)
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| 18 | Smolder time / Total puff interval |
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153.4–397.4 s/cig calculated from (105) 306 or 362 s/HTP stick, 1320 s/e-vapor product calculated from (107)
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| 19 | Product use topography | The complete pattern using an inhalable TNP, including puffing, mouth hold, inhalation, and exhalation |
A complex set of measurement parameters based on definitions included herein. The product use topography is assessed by two or more specialized instruments. The puffing topography is supplemented with separate measurements of inhalation and exhalation.
| (See Figure 2) |
| 20 | Mouth hold time | The time over which a puff is held in the oral cavity before inhalation or exhalation for an inhalable TNP The time placed between the gum and the lip (upper lip or cheek/jaw) for an oral TNP |
Time (s)
measured by observation, flow monitoring using a special instrument to assess inhaling and exhaling from an inhalable TNP (109); or
measured by observation the timing before it is put in and after taken out of the mouth for an oral TNP.
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0.86–1.0 s for each puff of a combustible cigarette (110) 30–60 min guided by the oral product instructions, placed between the gum and lip (upper lip or cheek/jaw) (64)
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| 21 | Mouth spill (MSp) | The amount or fraction of smoke, aerosol, or constituent that is spilt from the mouth after puffing and not inhaled by an inhalable TNP user |
Mass (mg, μg, ng, pg)
mass per inhalable tobacco product. Rate (%) fraction of smoke, aerosol, or constituents released from the mouth not inhaled
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| 22 | Inhalation | The act of moving puffed smoke/aerosol from the mouth into the trachea and respiratory space of an inhalable TNP user | See ‘Inhalation duration’ and ‘Inhalation volume’ |
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| 23 | Inhalation duration | The time from start of inhalation until start of exhalation phase of the breathing cycle |
Time (s) measured by flow monitoring using a special instrument to assess inhaling and exhaling (109); or measured with respiratory inductive plethysmography devices such as bands or vests, which record chest movements (57, 58).
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| 24 | Inhalation volume / Inhalation depth | The volume of inspiration into trachea and respiratory space |
Volume (mL) measured by flow monitoring using a special instrument to assess inhaling and exhaling (109); or measured with respiratory inductive plethysmography devices such as bands or vests, which record chest movements (57, 58).
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985.7–1231.3 mL for each puff of a combustible cigarette (110) 748–878 mL for each puff of a combustible cigarette was 25% of vital capacity (57) 833 mL for each puff of a combustible cigarette (58)
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| 25 | Exhalation | The act of expelling inhaled and puffed smoke/aerosol from the respiratory space and mouth or nasal passages of an inhalable TNP user | See ‘Exhalation duration’ and ‘Exhalation volume’ |
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| 26 | Exhalation duration | The time from end of inhalation until the end of the exhalation phase of the breathing cycle |
Time (s) measured by flow monitoring using a special instrument to assess inhaling and exhaling (109); or measured with respiratory inductive plethysmography devices such as bands or vests, which record chest movements (57, 58).
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| 27 | Exhalation volume | The volume of exhaled breath from the respiratory space after a puff and inhalation of an inhalable TNP |
Volume (mL) measured by flow monitoring using a special instrument to assess inhaling and exhaling (109); or measured with respiratory inductive plethysmography devices such as bands or vests, which record chest movements (57, 58).
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| 28 | Machine-derived yield / Machine yield | The amount of delivered smoke or aerosol constituents from the inhalable TNP under machine smoking/vaping conditions at a specified regime, e.g., ISO, Health Canada (2,15,102,103,104) |
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| 29 | Mouth level exposure (MLE) / Yield in-use (YIU) / Intake |
The amount of delivered smoke or aerosol constituents exiting the inhalable TNP into the mouth throughout human use The amount of given constituent extracted from the oral product when a given person uses that product |
Mass (mg, μg, ng, pg)
can be measured by duplication of the human puffing profile in a smoking/vaping machine;
can be estimated by used cigarette filter analysis techniques in terms of conventional cigarette;
measured by used oral product analysis techniques; or
estimated from extract fraction from placement of product and length of exposure.
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| 30 | Retention / Pulmonary retention | The difference between the amount of smoke or aerosol constituent inhaled and the amount of exhaled constituent over subsequent breathing cycles |
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For many smoke constituents, e.g., nicotine, retention is practically identical with the amount absorbed but for others, e.g., some PAH, retention does not equal absorption (46, 63)
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| 31 | Uptake / Amount absorbed | The amount of smoke, aerosol or extracted constituent which is absorbed into a human body through the mucosa of the mouth, respiratory tract, and lung |
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| Biomarker |
| 32 | Biomarker of exposure (BOE) |
A smoke constituent or its metabolite that is measured as a concentration in body fluids, excreta, or tissues (e.g., blood, urine, saliva, exhaled air, hair, sweat) BOE may also be measured as protein or DNA adducts
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Mass per unit volume (body fluid) Mass per mg creatinine (urine sample) Mass per 24 h (total urinary collection) Mass per mass other marker (e.g., tissues, urine, exhaled breath)
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Plasma cotinine (ng/mL) Urinary nicotine equivalents (mg/24 h) Urinary nicotine equivalents (mg/mg*creatinine) Exhaled CO (ppm) COHb (%) Certain BOE can be used as biomarkers of compliance in order to check whether study subjects use assigned product: compliance can be verified using highly specific markers especially with respect to long-term studies but also during study initiation / screening (e.g., cyanoethylvalin in blood as long-term BOE of smoking (114))
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| 33 | Biologically effective dose (BED) |
The amount of a smoke constituent or metabolite bound to a macromolecule (e.g., protein, DNA, RNA) of a specific tissue or organ that is thought to be mechanistically related to disease outcomes The biomarkers assessing the biologically effective dose are theoretically best link exposure (external and internal) to disease outcomes |
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| 34 | Biomarker of risk / Biomarker of potential harm (BOPH) | The measurement of a biological impact/effect due to exposure; these include early biological effects, such as oxidative stress, platelet activation, and inflammation |
Mass per unit volume (body fluid) Mass per mg creatinine (urine sample) Mass per 24 h (total urinary collection) Mass per mass other marker (e.g., tissues, urine, exhaled breath)
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White blood cell count (109/L, 103/μL) Soluble Intercellular adhesion molecule-1 (ng/mL) High-density lipoprotein (HDL) cholesterol (mg/dL, mmol/L) 8-Epi-prostaglandin F2α (ng/24 h, ng/g*creatinine) 11-Dehydrothromboxane B2 (ng/24 h, ng/g*creatinine)
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