Table 2.
Studies reporting original data from preliminary toxicological assessment of heated tobacco products (HTP) according to the types of studies performed, categories of HTPs, and comparator reference products.
| Author-date | Aerosol Chemistry | In Vitro | In Vivo | Other | HTP typea |
Reference cigaretteb | Test material generatione | Analytes / Assaysp |
|---|---|---|---|---|---|---|---|---|
| Zenzen 2012 | X | X | E | 2R4F CC |
ISO HPBf |
2) 49 HPHCs 3) Ames / NRU |
||
| Schaller 2016a | X | X | X | E | 3R4F | HCI ISO APRg |
2) 58 HPHCs 3) Ames / NRU / MLA 5) aerosol droplet size - MMAD |
|
| Oviedo 2016 | X | E | 3R4F | HCI | 4) OECD Test No. 413 /Systems toxicology endpoints | |||
| Schaller 2016b | X | E | 3R4F | HCI | 2) 58 HPHCs | |||
| Wong 2016 | X | E | 3R4F | HCI | 4) OECD Test No. 413 /Systems toxicology endpoints | |||
| Auer 2017 | X | E | CC; PDc |
ISO | 2) 8 VOCs; 16 PAHs; 3 inorganic compounds; Nicotine | |||
| Bekki 2017 | X | E | 1R5F; 3R4F |
HCI | 2) Nicotine; Tar; CO; 4 TSNAs | |||
| Farsalinos 2017 | X | E | CC | HCI LPVh |
2) Nicotine | |||
| Jaccard 2017 | X | E | 3R4F; CC |
HCI | 2) 44 compounds (Health Canada list) | |||
| Poynton 2017 | X | A | 3R4F | HCI CRM81i |
2) Untargeted GC scans; 113 compounds (FDA / HC) |
|||
| Jaunky 2018 | X | E | 3R4F | HCI | 3) NRU | |||
| Takahashie 2018 | X | X | A | 3R4F | HCI | 2) 43 Hoffmann analytes; propylene glycol, glycerol, triacetin, TPM, Nicotine, CO; 3) Ames / MN / NRU |
||
| Thorne 2018 | X | E | 3R4F | HCI | 3) Ames / NRU / MLA / Bhas cell transformation | |||
| Eaton 2018 | X | E | 3R4F | nak | 1) TGAq | |||
| Farsalinos 2018 | X | E | CC | HCI + 2 Intensel |
2) 5 carbonyls (acetaldehyde, acrolein, formaldehyde, propionaldehyde and crotonaldehyde) | |||
| Forster 2018 | X | X | E | 3R4F | HCI CRM81i |
2) 126 HPHCs 5) Physical analysis: particle diameter and number |
||
| Li 2018 | X | X | E | 3R4F | HCI ISO |
1) Simulated pyrolysis 2) TPM; water, tar, nicotine, propylene glycol, glycerin, CO, VOCs, aromatic amines, HCN, ammonia, TSNAs, phenol, PAHs |
||
| Mallock 2018 | X | E | PDd | HCI | 2) TPM; Nicotine, Water, Aldehydes (Acetaldehyde; acrolein; formaldehyde; crotonaldehyde) VOCs (1,3-Butadiene; Benzene; Isoprene; Styrene; Toluene) | |||
| Pacitto 2018 | X | E | PD | (-/2/10)m | 5) physical characteristics of the aerosol (Particle size distribution; particle volatilitiy) | |||
| Savareear 2018 | X | E | 3R4F | HCI | 2) Non targeted screening of VOCs from PP fraction of aerosols | |||
| Titz 2018 | X | C | 3R4F | HCI | 4) OECD413 / Systems toxicology endpoints | |||
| Godec, 2019 | X | E | 3R4F | HCI | 3) Ames / MLA | |||
| Thorne 2019a | X | E | 3R4F | HCI | 3) MLA | |||
| Thorne 2019b | X | E | 3R4F | HCI | 3) MN | |||
| McAdam 2019 | X | C, E | CC | Multiplen | 2) Total aerosol mass (AM); smoke particulate matter (TPM); Water; Nicotine; Glycerol | |||
| Salman 2019 | X | X | E | CC | HCI ISO |
2) Carbonyl compounds and total nicotine (free-base and protonated) and Reactive oxygen species (ROS) | ||
| Savareear 2019 | X | E | 3R4F | HCI ISO° |
2) non-targeted screening for PP components | |||
| Caruso 2021 | X | E | IR6F | HCI | 3) Cytotoxicity tests in Human H292 cells via ALI (Air-liquid interface) exposure: NRU; MTT; Annexin V apoptosis; |
|||
| Dusautoir 2021 | X | X | E | 3R4F | HCI (WA) | 2) Nicotine; Aldehydes, PAHs 3) BEAS-2B cells cell viability; Glutathione Content assay; Gene expression; inflammatory mediators (GM-CSF; GRO-α IL-1ẞ; IL-6; IL-8; IL-13; MCP-1; MIP-1 α, RANTES and INF-γ) |
a: HTP category as defined by CORESTA [23]: E = electrically heated tobacco product (eHTP); A = aerosol-heated tobacco product (aHTP); C = carbon-heated tobacco product (cHTP).
b: CC = marketed conventional cigarettes, PD = published data.
c: Published data based on reference [71].
d: Published data based on reference [12]
e: Test material generation as defined by the puffing regimen applied to produce the testing material characterized by puff volume (mL)/puff duration(s)/puff interval(s): ISO = International Organization for Standardization (35/2/60); HCI = Health Canada Intense (55/2.0/30). Other regimens specified by relevant footnotes: CRM81 = CORESTA recommended method (55/3/30); test material exposure; TPM = total particulate matter; GVP = gas–vapor phase; WA = whole aerosol; ALI = air–liquid interface.
f: HPB = human puffing behavior—nine different puffing regimens compared based on observed human topography studies (see [76] for details).
g: APR—test material also generated using five alternative puffing regimens based on human puffing behavior (see [56] for details).
h: LPV includes a long puff variant of the HCI regimen (55/4/30) in addition to the standard HCI regimen.
i: Reference cigarette 3R4F generation using HCI regimen; CRM81 for HTPs.
k: na = not applicable. A pyrolysis study was conducted based on 10 g of tobacco with 10 g wrapping paper heated in air or nitrogen in a platinum crucible up to 900 °C (see [16] for experimental details).
l: Products were tested using HCI and two more intense regimens (80/3/30 and 90/3/25).
m: Each test was performed with four puff profiles of five puffs for 2 s and an inter-puff time of 10 s. The puff volume was not specified; however, the flow rate was 1 L/min.
n: Five different regimens used with fixed 30-s puff interval and 20 puffs per device. The puff volume ranged from 20 mL to 150 mL and the duration from 2 s to 5 s
o: HCI regimen used for the HTPs; ISO for 3R4F.
p:1) Brief description of the pyrolysis method applied; 2) analytes measured in aerosol chemistry studies represented as the total number of analytes; plus, details of specific lists as given by the authors; 3) in vitro assays used: NRU = neutral red uptake, MLA = mammalian mouse lymphoma assay, MN = micronucleus, other tests as described; 4) in vivo protocol applied: OECD413 = Organization for Economic Cooperation and Development Test Guideline 413: Repeated dose inhalation toxicity; 5) other assays are briefly described. Please refer to the original papers for full details.
q: TGA = thermogravimetric analysis with Pyris 1 TGA system in air or nitrogen: 5 °C/min from ambient temperature to 240 °C, held for 5 min at 240 °C, and continued ramping to 900 °C.