Table 1
Ambient conditions representing the climatic zones considered for the study.
| Conditions (abbreviation) | Temperature (°C) | Relative humidity (% RH) |
|---|---|---|
| ISOa (S) | 22 ± 2 | 60 ± 5 |
| Hot and Very Humid (H) | 30 ± 2 | 75 ± 5 |
| Hot and Dry (D) | 30 ± 2 | 35 ± 5 |

Figure 1
Example of the non-inferiority test used in the determination of threshold of robust reduction across A, B, C, D and E conditions. Error bars delimit 0.95 confidence intervals of the means. The lowest-bound (D) is right above 65% and the considered HPHC therefore belongs to the corresponding threshold category (i.e., ≥65%).
Table 2
Puff count for 3R4F as function of climatic conditions.
| Conditions (abbreviation) | Puff number mean ± SD (n) |
|---|---|
| ISO (S) | 10.58 ± 0.40 (83) |
| Hot and Very Humid (H) | 12.26 ± 1.09 (83) |
| Hot and Dry (D) | 9.18 ± 0.62 (84) |

Figure 2
Average reduction in HPHC in volume-adjusted yields. Comparison of overall relative reduction across various ambient conditions using volume-adjusted values. THS 2.2 aerosol levels are calculated as a percentage of 3R4F cigarette mainstream smoke levels. D, S, and H stand for Dry (Hot and Dry), ISO (Mediterranean), and Humid (Hot and Very Humid) conditions. The respective conditions identified by D, S, and H are described in Table 1. The number of HPHCs (n) considered for calculation of the average reductions varied among the different combinations of conditions.

Figure 3
Average reduction in nicotine-adjusted HPHC yields. Comparison of overall relative reduction across various ambient conditions using nicotine-adjusted values. THS 2.2 aerosol levels are calculated as a percentage of 3R4F cigarette mainstream smoke levels. D, S, and H stand for Dry (Hot and Dry), ISO (Mediterranean), and Humid (Hot and Very Humid) conditions. The respective conditions identified by D, S, and H are described in Table 1. The number of HPHCs (n) considered for calculation of the average reductions varied among the different combinations of conditions.
Table 3
Mean relative reduction (CI95%) and threshold calculated with unvaried 3R4F conditions (ISO climatic). HPHCs (n = 7) impacted by change of reduction threshold between ISO and extreme climatic conditions.
| Compound | THS 2.2 and 3R4F ISO cond. (Threshold) | THS 2.2 lowesta 3R4F ISO cond. (Threshold) | Lowestb bound |
|---|---|---|---|
| HCN | 99.4 ± 0.1% (≥99) | 99.1 ± 0.2% (≥95) | D |
| m-Cresol | 99.2 ± 0.1% (≥99) | 99.0 ± 0.2% (≥95) | H |
| Toluene | 99.2 ± 0.1% (≥99) | 99.0 ± 0.1% (≥95) | H |
| Acetone | 95.7 ± 0.6% (≥95) | 95.2 ± 0.6% (≥90) | H |
| Acetamide | 78.4 ± 2.0% (≥75) | 77.16 ± 2.2% (≥70) | H |
| Ammonia | 68.1 ± 2.7% (≥65) | 62.1 ± 3.1% (≥55) | D |
| Hg | 52.7 ± 4.8% (≥45) | 49.2 ± 5.1% (≥40) | D |
a Relative reduction corresponding to extreme climatic condition used for testing THS 2.2 which resulted in the lowest-bound value
Abbreviations: CI95% = 95% confidence interval; cond. = conditions; HCN = hydrogen cyanide; Hg = mercury; HPHC = harmful and potentially harmful constituent; D = Hot and Dry; H = Hot and Very Humid
Table 4
Mean differences (CI95%) of volume-adjusted yields in “Hot and Very Humid” relative to ISO climatic conditions.
| Compound | 3R4F (%) | THS 2.2 (%) |
|---|---|---|
| Acetaldehyde | −11 ± 7 | 14 ± 15 a |
| Acetamide | −33 ± 9 | 6 ± 8 a |
| Acrylamide | −49 ± 10 | −4 ± 9 a |
| Ammonia | −22 ± 9 | 3 ± 7 a |
| Butyraldehyde | −13 ± 8 | 6 ± 11 a |
| Ethylene oxide | −11 ± 6 | 33 ± 11 |
| Formaldehyde | −55 ± 15 | −11 ± 24 a |
| Hg | −18 ± 11 | 7 ± 7.1 a |
| MEK | −13 ± 8 | 27 ± 23 |
| NAB | −21 ± 7 | 1 ± 9 a |
| Nitrobenzene | −59 ± 9 | −35 ± 6 |
| o-Cresol | −62 ± 12 | 40 ± 26 |
| p-Cresol | −65 ± 11 | 35 ± 23 |
| Phenol | −76 ± 14 | 25 ± 23 |
| Pyridine | −18 ± 7 | −3 ± 5 a |
Table 5
HPHCs categorized by thresholds of robust reduction: THS 2.2 over all climatic conditions vs. 3R4F ISO climatic conditions.
| Compounds | n | Threshold |
|---|---|---|
| 1-Aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 1,3-butadiene, acrylonitrile, benzene, Cd, ethylene oxide, isoprene, p-cresol | 10 | ≥99 |
| 4-Aminobiphenyl, CO, crotonaldehyde, HCN, MEK, m-cresol, NAB, NNK, NNN, NAT, NO, NOx, o-cresol, o-toluidine, Pb, quinoline, resorcinol, styrene, toluene, vinyl chloride | 20 | ≥95 |
| Acetone, acrolein, benzo[a]anthracene, benzo[a]pyrene, dibenz[a,h]anthracene, formaldehyde, hydroquinone, propylene oxide, pyrene | 9 | ≥90 |
| As, acetaldehyde, propionaldehyde, phenol | 4 | ≥85 |
| Catechol, pyridine | 2 | ≥80 |
| Butyraldehyde, nitrobenzene | 2 | ≥75 |
| Acetamide | 1 | ≥70 |
| – | 0 | ≥65 |
| Acrylamide | 1 | ≥60 |
| Ammonia | 1 | ≥55 |
| – | 0 | ≥50 |
| – | 0 | ≥45 |
| Hg | 1 | ≥40 |
Table 6
HPHCs categorized by thresholds of robust reduction: THS 2.2 vs. 3R4F over all climatic conditions.
| Compounds | n | Threshold |
|---|---|---|
| 1-Aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 1,3-butadiene, acrylonitrile, benzene, Cd, isoprene | 8 | ≥99 |
| 4-Aminobiphenyl, CO, crotonaldehyde, ethylene oxide, HCN, m-cresol, NNK, NNN, NAT, NO, NOx, o-toluidine, p-cresol, Pb, quinoline, resorcinol, styrene toluene, vinyl chloride | 19 | ≥95 |
| Acetone, acrolein, benzo[a]anthracene, benzo[a]pyrene, dibenz[a,h]anthracene, hydroquinone, MEK, NAB, o-cresol, propylene oxide, pyrene | 11 | ≥90 |
| As, propionaldehyde, | 2 | ≥85 |
| Acetaldehyde, catechol, formaldehyde | 3 | ≥80 |
| Pyridine | 1 | ≥75 |
| Butyraldehyde | 1 | ≥70 |
| – | 0 | ≥65 |
| Acetamide | 1 | ≥60 |
| Nitrobenzene | 1 | ≥55 |
| Ammonia | 1 | ≥50 |
| – | 0 | ≥45 |
| – | 0 | ≥40 |
| Acrylamide, Hg, phenol | 3 | <40 |
[i] Abbreviations: As = arsenic; CO = carbon monoxide; HCN = hydrogen cyanide; Hg = mercury; HPHC = harmful and potentially harmful constituent; MEK = methyl ethyl ketone; NAB = N-nitrosoanabasine; NAT = N-nitrosoanatabine; NNK = 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone; NNN = N-nitrosonornicotine; NO = nitrogen oxide; Nox = nitrogen oxides; Pb = lead

Figure 4
Cases substantially impacted by change in the climatic conditions used for smoking the 3R4F reference cigarette. Error bars delimit 0.95 confidence intervals of the respective means. The dashed lines indicate the closest threshold category sitting below the lowest-bound of the confidence intervals considered across all conditions. With the same principle, the solid lines indicate the threshold category defined for THS 2.2 relative to 3R4F under ISO climatic conditions. Threshold categories consist of a series of predefined discrete values. Contiguous graphs were paired by compounds, with relative reduction presented on the left and volume-adjusted yields on the right. The respective conditions identified by D, S, and H are described in Table 1.
Abbreviations: HPHC = harmful and potentially harmful constituent; Hg = mercury.
Appendix A
Mean (± SD) of compound deliveries investigated in 3R4F mainstream smoke and THS 2.2 aerosol, measured under various climatic conditions.
| Item | 3R4F | THS 2.2 | Unit | ||||
|---|---|---|---|---|---|---|---|
| Identification | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | |
| ISO parameters and product-specific constituents | |||||||
| Glycerol | 2.28 ± 0.15 | 2.37 ± 0.21 | 2.26 ± 0.19 | 4.25 ± 0.20 | 4.68 ± 0.29 | 4.16 ± 0.16 | [mg/item] |
| Nicotine | 2.01 ± 0.14 | 1.91 ± 0.14 | 1.41 ± 0.14 | 1.46 ± 0.04 | 1.42 ± 0.04 | 1.24 ± 0.06 | [mg/item] |
| NFDPM | 30.9 ± 1.0 | 31.2 ± 1.9 | 38.3 ± 1.5 | 11.3 ± 1.1 | 12.2 ± 0.9 | 12.6 ± 1.2 | [mg/item] |
| Carbon monoxide | 26.9 ± 0.7 | 30.5 ± 0.9 | 31.7 ± 1.1 | 0.45 ± 0.04 | 0.61 ± 0.02 | 0.47 ± 0.02 | [mg/item] |
| Ammonia | 37.8 ± 2.9 | 29.2 ± 1.9 | 29.1 ± 2.1 | 12.5 ± 0.4 | 10.5 ± 0.4 | 10.8 ± 0.7 | [μg/item] |
| Carbonyls | |||||||
| Formaldehyde | 100.9 ± 11.8 | 64.9 ± 5.1 | 31.7 ± 1.5 | 4.69 ± 0.99 | 4.67 ± 0.44 | 4.12 ± 0.99 | [μg/item] |
| Acetaldehyde | 1730 ± 50 | 1670 ± 90 | 1630 ± 100 | 190 ± 16 | 212 ± 20 | 240 ± 28 | [μg/item] |
| Acetone | 758 ± 23 | 746 ± 49 | 707 ± 45 | 36.3 ± 4.8 | 37.2 ± 3.8 | 41.7 ± 5.3 | [μg/item] |
| Acrolein | 191 ± 6 | 186 ± 11 | 169 ± 13 | 9.22 ± 1.39 | 9.86 ± 1.45 | 13.25 ± 2.85 | [μg/item] |
| Propionaldehyde | 134 ± 3 | 133 ± 9 | 131 ± 8 | 12.4 ± 1.5 | 13.9 ± 1.5 | 17.3 ± 2.3 | [μg/item] |
| Crotonaldehyde | 51.9 ± 2.3 | 50.9 ± 3.9 | 47.8 ± 3.3 | 1.73 ± 0.23 | 1.81 ± 0.20 | 2.18 ± 0.39 | [μg/item] |
| Methyl ethyl ketone | 204 ± 6 | 209 ± 17 | 199 ± 13 | 7.38 ± 1.02 | 7.96 ± 0.97 | 10.01 ± 1.45 | [μg/item] |
| Butyraldehyde | 63.6 ± 2.7 | 62.3 ± 4.7 | 59.5 ± 4.3 | 13.0 ± 1.0 | 14.4 ± 1.2 | 15.2 ± 1.2 | [μg/item] |
| Hydrogen cyanide | 438 ± 20 | 475 ± 19 | 467 ± 25 | 4.74 ± 0.33 | 3.09 ± 0.44 | 3.04 ± 0.18 | [μg/item] |
| Mercury | 3.70 ± 0.22 | 4.44 ± 0.32 | 4.08 ± 0.48 | 2.42 ± 0.10 | 2.25 ± 0.06 | 2.41 ± 0.15 | [ng/item] |
| Trace metals (except mercury) | |||||||
| Cadmium | 93.9 ± 6.6 | 101.7 ± 7.1 | 116.6 ± 6.0 | 0.13* | 0.17* | 0.20* | [ng/item] |
| Lead | 26.4* | 26.9 ± 1.1 | 30.5 ± 1.6 | 0.94* | 0.49* | 1.17* | [ng/item] |
| Chromium | 11.9* | 17.4* | 17.4* | 3.31* | 3.31* | 3.31* | [ng/item] |
| Nickel | 12.9* | 18.9* | 12.9* | 15.9* | 15.9* | 15.9* | [ng/item] |
| Arsenic | 8.23 ± 0.67 | 8.63 ± 0.78 | 8.94 ± 0.38 | 1.24* | 1.20* | 1.20* | [ng/item] |
| Selenium | 4.42* | 4.42* | 4.42* | 0.60* | 0.71* | 0.83* | [ng/item] |
| Nitrogen oxides | |||||||
| NO | 446 ± 26 | 489 ± 16 | 539 ± 56 | 16.3 ± 0.7 | 18.3 ± 1.0 | 18.2 ± 0.2 | [μg/item] |
| NOx | 483 ± 25 | 538 ± 19 | 601 ± 66 | 17.3 ± 0.7 | 19.5 ± 1.2 | 19.0 ± 0.4 | [μg/item] |
| Volatiles | |||||||
| 1,3-Butadiene | 63.6 ± 1.9 | 62.4 ± 3.2 | 70.0 ± 2.7 | 0.25 ± 0.01 | 0.28 ± 0.03 | 0.32 ± 0.02 | [μg/item] |
| Isoprene | 804 ± 28 | 841 ± 50 | 919 ± 37 | 1.83 ± 0.14 | 2.19 ± 0.17 | 2.60 ± 0.20 | [μg/item] |
| Acrylonitrile | 30.6 ± 1.1 | 32.4 ± 1.1 | 32.7 ± 1.2 | 0.18 ± 0.02 | 0.17 ± 0.03 | 0.19 ± 0.03 | [μg/item] |
| Benzene | 97.8 ± 3.4 | 101.8 ± 3.8 | 106.5 ± 3.2 | 0.59 ± 0.03 | 0.60 ± 0.03 | 0.61 ± 0.02 | [μg/item] |
| Toluene | 185 ± 7 | 198 ± 7 | 209 ± 8 | 1.85 ± 0.12 | 2.11 ± 0.16 | 2.25 ± 0.15 | [μg/item] |
| Semi-volatiles | |||||||
| Pyridine | 35.7 ± 3.1 | 38.3 ± 1.3 | 34.7 ± 2.2 | 5.76 ± 0.34 | 7.47 ± 0.25 | 7.26 ± 0.23 | [μg/item] |
| Quinoline | 0.51 ± 0.05 | 0.48 ± 0.03 | 0.32* | 0.013* | 0.013* | 0.013* | [μg/item] |
| Styrene | 23.0 ± 1.1 | 25.7 ± 0.9 | 26.5 ± 1.3 | 0.62 ± 0.03 | 0.64 ± 0.03 | 0.69 ± 0.03 | [μg/item] |
| Nitrobenzene | 0.43 ± 0.03 | 0.52 ± 0.04 | 0.30 ± 0.02 | 0.087 ± 0.004 | 0.134 ± 0.008 | 0.087 ± 0.007 | [μg/item] |
| Phenols and acid derivatives | |||||||
| Hydroquinone | 76.2 ± 4.3 | 84.1 ± 1.4 | 96.5 ± 2.1 | 5.45 ± 0.85 | 7.75 ± 0.55 | 8.67 ± 0.81 | [μg/item] |
| Resorcinol | 1.70 ± 0.08 | 1.87 ± 0.05 | 1.94 ± 0.03 | 0.029 ± 0.004 | 0.039 ± 0.004 | 0.056 ± 0.008 | [μg/item] |
| Catechol | 91.7 ± 6.1 | 89.7 ± 1.6 | 79.2 ± 1.4 | 11.7 ± 1.3 | 14.9 ± 0.8 | 15.6 ± 1.3 | [μg/item] |
| Phenol | 19.69 ± 2.67 | 13.94 ± 1.25 | 3.39 ± 0.45 | 1.45 ± 0.32 | 1.50 ± 0.17 | 1.86 ± 0.12 | [μg/item] |
| p-Cresol | 11.77 ± 1.44 | 9.80 ± 0.70 | 3.60 ± 0.35 | 0.069 ± 0.013 | 0.071 ± 0.008 | 0.096 ± 0.009 | [μg/item] |
| m-Cresol | 4.57 ± 0.55 | 3.81 ± 0.28 | 1.43 ± 0.12 | 0.033 ± 0.006 | 0.035 ± 0.004 | 0.046 ± 0.003 | [μg/item] |
| o-Cresol | 5.95 ± 0.77 | 4.91 ± 0.41 | 1.94 ± 0.19 | 0.067 ± 0.015 | 0.082 ± 0.009 | 0.114 ± 0.012 | [μg/item] |
| Acetamide | 11.80 ± 1.00 | 12.84 ± 0.51 | 8.85 ± 0.99 | 2.78 ± 0.26 | 3.21 ± 0.11 | 3.38 ± 0.17 | [μg/item] |
| Acrylamide | 4.69 ± 0.50 | 4.42 ± 0.26 | 2.34 ± 0.29 | 1.57 ± 0.15 | 1.75 ± 0.09 | 1.68 ± 0.07 | [μg/item] |
| Polycyclic aromatic hydrocarbons | |||||||
| Pyrene | 89.1 ± 7.0 | 80.8 ± 2.6 | 102.5 ± 10.5 | 7.27 ± 1.31 | 5.66 ± 0.49 | 5.85 ± 1.02 | [ng/item] |
| Benzo[a]anthracene | 28.5 ± 1.7 | 26.8 ± 1.9 | 30.2 ± 2.5 | 1.51 ± 0.28 | 1.39 ± 0.08 | 1.39 ± 0.16 | [ng/item] |
| Benzo[a]pyrene | 14.5 ± 0.9 | 12.9 ± 1.0 | 16.1 ± 1.6 | 1.03* | 1.00* | 1.00* | [ng/item] |
| Dibenz[a,h]anthracene | 1.47 ± 0.14 | 1.43 ± 0.13 | 1.53 ± 0.18 | 0.10* | 0.10* | 0.10* | [ng/item] |
| Epoxides and vinyl chloride | |||||||
| Vinyl chloride | 76.8 ± 4.2 | 83.0 ± 2.7 | 86.9 ± 4.2 | 3.73* | 3.73* | 3.73* | [ng/item] |
| Ethylene oxide | 32.5 ± 1.4 | 36.0 ± 1.2 | 37.1 ± 2.6 | 0.27 ± 0.01 | 0.27 ± 0.01 | 0.35 ± 0.03 | [μg/item] |
| Propylene oxide | 1.47 ± 0.04 | 1.64 ± 0.06 | 1.73 ± 0.05 | 0.13 ± 0.00 | 0.15 ± 0.01 | 0.16 ± 0.02 | [μg/item] |
| Aromatic amines | |||||||
| 1-Aminonaphthalene | 17.1 ± 1.1 | 18.7 ± 1.0 | 20.8 ± 1.6 | 0.070* | 0.070* | 0.070* | [ng/item] |
| 2-Aminonaphthalene | 10.7 ± 0.4 | 11.9 ± 0.9 | 16.0 ± 1.3 | 0.017* | 0.016* | 0.088* | [ng/item] |
| 3-Aminobiphenyl | 3.41 ± 0.16 | 3.80 ± 0.27 | 5.13 ± 0.61 | 0.029* | 0.029* | 0.029* | [ng/item] |
| 4-Aminobiphenyl | 2.58 ± 0.10 | 2.96 ± 0.17 | 4.08 ± 0.55 | 0.032 ± 0.013 | 0.047* | 0.073 ± 0.018 | [ng/item] |
| o-Toluidine | 96.3 ± 16.4 | 94.7 ± 9.2 | 78.5 ± 3.3 | 0.65 ± 0.26 | 1.14 ± 0.09 | 0.62 ± 0.48 | [ng/item] |
| Tobacco-specific nitrosamines | |||||||
| NNN | 321 ± 37 | 279 ± 9 | 219 ± 17 | 4.91 ± 0.30 | 5.38 ± 0.28 | 5.17 ± 0.30 | [ng/item] |
| NAT | 326 ± 12 | 282 ± 14 | 226 ± 17 | 11.3 ± 0.9 | 11.8 ± 0.7 | 10.6 ± 0.5 | [ng/item] |
| NAB | 40.1 ± 1.9 | 34.2 ± 2.1 | 28.1 ± 1.7 | 1.73 ± 0.13 | 1.75 ± 0.11 | 1.77 ± 0.09 | [ng/item] |
| NNK | 278 ± 22 | 276 ± 21 | 214 ± 17 | 5.52 ± 0.55 | 5.90 ± 0.52 | 5.47 ± 0.33 | [ng/item] |
[i] Abbreviations: NAB = N-nitrosoanabasine; NAT = N-nitrosoanatabine; NNK = 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone; NNN = N-nitrosonornicotine; NO = nitrogen oxide; NOx = nitrogen oxides; NFDPM = nicotine free dry particulate matter; SD = standard deviation For results <LOD, the values used in the calculation of mean and standard deviation were estimated by the LOD; for results <LOQ but >LOD, the values were estimated by the LOQ.
Appendix B
Mean (± SD) of nicotine-adjusted yields of compounds investigated in 3R4F mainstream smoke and THS 2.2 aerosol, measured under various climatic conditions.
| Item | 3R4F | THS 2.2 | Unit | ||||
|---|---|---|---|---|---|---|---|
| Identification | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | |
| ISO parameters and product-specific constituents | |||||||
| Glycerol | 1.13 ± 0.08 | 1.24 ± 0.11 | 1.61 ± 0.13 | 2.91 ± 0.14 | 3.29 ± 0.20 | 3.37 ± 0.13 | [mg/item/mg nicotine] |
| Nicotine | 1.00 ± 0.07 | 1.00 ± 0.07 | 1.00 ± 0.10 | 1.00 ± 0.03 | 1.00 ± 0.03 | 1.00 ± 0.05 | [mg/item/mg nicotine] |
| NFDPM | 15.4 ± 0.5 | 16.4 ± 1.0 | 27.2 ± 1.1 | 7.73 ± 0.79 | 8.60 ± 0.64 | 10.22 ± 0.99 | [mg/item/mg nicotine] |
| Carbon monoxide | 13.4 ± 0.4 | 16.0 ± 0.5 | 22.5 ± 0.8 | 0.31 ± 0.03 | 0.43 ± 0.01 | 0.38 ± 0.02 | [mg/item/mg nicotine] |
| Ammonia | 18.8 ± 1.4 | 15.3 ± 1.0 | 20.6 ± 1.5 | 8.53 ± 0.27 | 7.40 ± 0.28 | 8.72 ± 0.54 | [μg/item/mg nicotine] |
| Carbonyls | |||||||
| Formaldehyde | 50.2 ± 5.9 | 34.0 ± 2.7 | 22.5 ± 1.1 | 3.21 ± 0.68 | 3.29 ± 0.31 | 3.34 ± 0.80 | [μg/item/mg nicotine] |
| Acetaldehyde | 863 ± 24 | 875 ± 46 | 1154 ± 74 | 130 ± 11 | 149 ± 14 | 194 ± 22 | [μg/item/mg nicotine] |
| Acetone | 378 ± 11 | 391 ± 26 | 502 ± 32 | 24.9 ± 3.3 | 26.2 ± 2.7 | 33.7 ± 4.3 | [μg/item/mg nicotine] |
| Acrolein | 95.1 ± 3.0 | 97.5 ± 5.9 | 120.0 ± 9.3 | 6.31 ± 0.95 | 6.94 ± 1.02 | 10.72 ± 2.31 | [μg/item/mg nicotine] |
| Propionaldehyde | 66.9 ± 1.3 | 69.7 ± 4.9 | 92.8 ± 5.8 | 8.46 ± 1.01 | 9.81 ± 1.04 | 13.98 ± 1.84 | [μg/item/mg nicotine] |
| Crotonaldehyde | 25.9 ± 1.1 | 26.7 ± 2.1 | 33.9 ± 2.3 | 1.19 ± 0.16 | 1.27 ± 0.14 | 1.77 ± 0.32 | [μg/item/mg nicotine] |
| Methyl ethyl ketone | 102 ± 3 | 110 ± 9 | 141 ± 9 | 5.05 ± 0.70 | 5.60 ± 0.68 | 8.10 ± 1.17 | [μg/item/mg nicotine] |
| Butyraldehyde | 31.7 ± 1.3 | 32.6 ± 2.5 | 42.2 ± 3.1 | 8.90 ± 0.65 | 10.12 ± 0.81 | 12.30 ± 0.97 | [μg/item/mg nicotine] |
| Hydrogen cyanide | 218 ± 10 | 249 ± 10 | 331 ± 18 | 3.24 ± 0.23 | 2.17 ± 0.31 | 2.46 ± 0.14 | [μg/item/mg nicotine] |
| Mercury | 1.84 ± 0.11 | 2.33 ± 0.17 | 2.89 ± 0.34 | 1.66 ± 0.07 | 1.58 ± 0.04 | 1.95 ± 0.12 | [ng/item/mg nicotine] |
| Trace metals (except mercury) | |||||||
| Cadmium | 46.8 ± 3.3 | 53.3 ± 3.7 | 82.7 ± 4.2 | 0.088* | 0.117* | 0.165* | [ng/item/mg nicotine] |
| Lead | 13.1* | 14.1 ± 0.6 | 21.6 ± 1.1 | 0.64* | 0.34* | 0.95* | [ng/item/mg nicotine] |
| Chromium | 5.93* | 9.14* | 12.38* | 2.27* | 2.33* | 2.68* | [ng/item/mg nicotine] |
| Nickel | 6.42* | 9.92* | 9.15* | 10.9* | 11.2* | 12.9* | [ng/item/mg nicotine] |
| Arsenic | 4.10 ± 0.33 | 4.52 ± 0.41 | 6.34 ± 0.27 | 0.85* | 0.84* | 0.97* | [ng/item/mg nicotine] |
| Selenium | 2.20* | 2.32* | 3.14* | 0.41* | 0.50* | 0.67* | [ng/item/mg nicotine] |
| Nitrogen oxides | |||||||
| NO | 222 ± 13 | 256 ± 9 | 382 ± 40 | 11.2 ± 0.5 | 12.8 ± 0.7 | 14.8 ± 0.2 | [μg/item/mg nicotine] |
| NOx | 241 ± 12 | 282 ± 10 | 426 ± 47 | 11.8 ± 0.5 | 13.7 ± 0.8 | 15.4 ± 0.3 | [μg/item/mg nicotine] |
| Phenols and acid derivatives | |||||||
| Hydroquinone | 38.0 ± 2.2 | 44.1 ± 0.7 | 68.5 ± 1.5 | 3.73 ± 0.58 | 5.46 ± 0.39 | 7.02 ± 0.65 | [μg/item/mg nicotine] |
| Resorcinol | 0.85 ± 0.04 | 0.98 ± 0.02 | 1.38 ± 0.02 | 0.020 ± 0.003 | 0.027 ± 0.003 | 0.046 ± 0.006 | [μg/item/mg nicotine] |
| Catechol | 45.7 ± 3.0 | 47.0 ± 0.8 | 56.2 ± 1.0 | 8.03 ± 0.88 | 10.50 ± 0.55 | 12.61 ± 1.01 | [μg/item/mg nicotine] |
| Phenol | 9.81 ± 1.33 | 7.30 ± 0.65 | 2.41 ± 0.32 | 0.99 ± 0.22 | 1.06 ± 0.12 | 1.51 ± 0.09 | [μg/item/mg nicotine] |
| p-Cresol | 5.86 ± 0.72 | 5.13 ± 0.37 | 2.55 ± 0.25 | 0.047 ± 0.009 | 0.050 ± 0.005 | 0.078 ± 0.007 | [μg/item/mg nicotine] |
| m-Cresol | 2.28 ± 0.28 | 2.00 ± 0.15 | 1.01 ± 0.09 | 0.022 ± 0.004 | 0.024 ± 0.003 | 0.037 ± 0.003 | [μg/item/mg nicotine] |
| o-Cresol | 2.96 ± 0.38 | 2.58 ± 0.21 | 1.38 ± 0.13 | 0.046 ± 0.011 | 0.058 ± 0.006 | 0.092 ± 0.010 | [μg/item/mg nicotine] |
| Acetamide | 5.87 ± 0.50 | 6.73 ± 0.27 | 6.28 ± 0.71 | 1.90 ± 0.18 | 2.26 ± 0.08 | 2.74 ± 0.14 | [μg/item/mg nicotine] |
| Acrylamide | 2.34 ± 0.25 | 2.32 ± 0.13 | 1.66 ± 0.21 | 1.08 ± 0.11 | 1.23 ± 0.06 | 1.36 ± 0.06 | [μg/item/mg nicotine] |
| Polycyclic aromatic hydrocarbons | |||||||
| Pyrene | 44.4 ± 3.5 | 42.4 ± 1.4 | 72.7 ± 7.4 | 4.98 ± 0.90 | 3.98 ± 0.35 | 4.74 ± 0.82 | [ng/item/mg nicotine] |
| Benzo[a]anthracene | 14.2 ± 0.9 | 14.1 ± 1.0 | 21.4 ± 1.8 | 1.04 ± 0.19 | 0.98 ± 0.06 | 1.12 ± 0.13 | [ng/item/mg nicotine] |
| Benzo[a]pyrene | 7.21 ± 0.47 | 6.74 ± 0.53 | 11.46 ± 1.12 | 0.70* | 0.70* | 0.81* | [ng/item/mg nicotine] |
| Dibenz[a,h]anthracene | 0.73 ± 0.07 | 0.75 ± 0.07 | 1.08 ± 0.13 | 0.068* | 0.070* | 0.081* | [ng/item/mg nicotine] |
| Volatiles | |||||||
| 1,3-Butadiene | 31.7 ± 1.0 | 32.7 ± 1.7 | 49.7 ± 1.9 | 0.17 ± 0.01 | 0.20 ± 0.02 | 0.26 ± 0.02 | [μg/item/mg nicotine] |
| Isoprene | 401 ± 14 | 441 ± 26 | 652 ± 26 | 1.25 ± 0.10 | 1.54 ± 0.12 | 2.10 ± 0.16 | [μg/item/mg nicotine] |
| Acrylonitrile | 15.2 ± 0.6 | 17.0 ± 0.6 | 23.2 ± 0.9 | 0.12 ± 0.01 | 0.12 ± 0.02 | 0.15 ± 0.02 | [μg/item/mg nicotine] |
| Benzene | 48.7 ± 1.7 | 53.3 ± 2.0 | 75.6 ± 2.3 | 0.40 ± 0.02 | 0.42 ± 0.02 | 0.50 ± 0.02 | [μg/item/mg nicotine] |
| Toluene | 92.3 ± 3.4 | 104.0 ± 3.9 | 148.4 ± 6.0 | 1.26 ± 0.08 | 1.48 ± 0.11 | 1.82 ± 0.12 | [μg/item/mg nicotine] |
| Semi-volatiles | |||||||
| Pyridine | 17.8 ± 1.5 | 20.1 ± 0.7 | 24.6 ± 1.6 | 3.95 ± 0.23 | 5.26 ± 0.18 | 5.88 ± 0.18 | [μg/item/mg nicotine] |
| Quinoline | 0.25 ± 0.02 | 0.25 ± 0.01 | 0.23* | 0.0089* | 0.0091* | 0.0105* | [μg/item/mg nicotine] |
| Styrene | 11.5 ± 0.5 | 13.5 ± 0.5 | 18.8 ± 0.9 | 0.42 ± 0.02 | 0.45 ± 0.02 | 0.56 ± 0.02 | [μg/item/mg nicotine] |
| Nitrobenzene | 0.21 ± 0.02 | 0.27 ± 0.02 | 0.21 ± 0.01 | 0.060 ± 0.003 | 0.094 ± 0.005 | 0.071 ± 0.005 | [μg/item/mg nicotine] |
| Epoxides and vinyl chloride | |||||||
| Vinyl chloride | 38.2 ± 2.1 | 43.5 ± 1.4 | 61.7 ± 3.0 | 2.55* | 2.62* | 3.02* | [ng/item/mg nicotine] |
| Ethylene oxide | 16.2 ± 0.7 | 18.9 ± 0.6 | 26.4 ± 1.8 | 0.18 ± 0.01 | 0.19 ± 0.01 | 0.29 ± 0.02 | [μg/item/mg nicotine] |
| Propylene oxide | 0.73 ± 0.02 | 0.86 ± 0.03 | 1.23 ± 0.03 | 0.088 ± 0.003 | 0.109 ± 0.006 | 0.126 ± 0.012 | [μg/item/mg nicotine] |
| Aromatic amines | |||||||
| 1-Aminonaphthalene | 8.50 ± 0.54 | 9.79 ± 0.50 | 14.73 ± 1.17 | 0.048* | 0.049* | 0.057* | [ng/item/mg nicotine] |
| 2-Aminonaphthalene | 5.34 ± 0.22 | 6.26 ± 0.46 | 11.34 ± 0.90 | 0.011* | 0.011* | 0.071* | [ng/item/mg nicotine] |
| 3-Aminobiphenyl | 1.70 ± 0.08 | 1.99 ± 0.14 | 3.64 ± 0.43 | 0.020* | 0.020* | 0.023* | [ng/item/mg nicotine] |
| 4-Aminobiphenyl | 1.29 ± 0.05 | 1.55 ± 0.09 | 2.90 ± 0.39 | 0.022 ± 0.009 | 0.033* | 0.059 ± 0.014 | [ng/item/mg nicotine] |
| o-Toluidine | 47.9 ± 8.2 | 49.6 ± 4.8 | 55.7 ± 2.3 | 0.44 ± 0.18 | 0.81 ± 0.06 | 0.50 ± 0.38 | [ng/item/mg nicotine] |
| Tobacco-specific nitrosamines | |||||||
| NNN | 160 ± 19 | 146 ± 5 | 155 ± 12 | 3.36 ± 0.21 | 3.79 ± 0.20 | 4.19 ± 0.25 | [ng/item/mg nicotine] |
| NAT | 162 ± 6 | 148 ± 8 | 160 ± 12 | 7.75 ± 0.63 | 8.34 ± 0.46 | 8.57 ± 0.37 | [ng/item/mg nicotine] |
| NAB | 20.0 ± 0.9 | 17.9 ± 1.1 | 19.9 ± 1.2 | 1.18 ± 0.09 | 1.23 ± 0.08 | 1.43 ± 0.08 | [ng/item/mg nicotine] |
| NNK | 138 ± 11 | 145 ± 11 | 152 ± 12 | 3.78 ± 0.38 | 4.15 ± 0.37 | 4.43 ± 0.27 | [ng/item/mg nicotine] |
[i] Abbreviations: NAB = N-nitrosoanabasine; NAT = N-nitrosoanatabine; NNK = 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone; NNN = N-nitrosonornicotine; NO = nitrogen oxide; NOx = nitrogen oxides; NFDPM = nicotine free dry particulate matter; SD = standard deviation For results <LOD, the values used in the calculation of mean and standard deviation were estimated by the LOD; for results <LOQ but >LOD, the values were estimated by the LOQ.
Appendix C
Mean (± SD) of volume-adjusted yields of compounds investigated in 3R4F mainstream smoke and THS 2.2 aerosol, measured under various climatic conditions.
| Item | 3R4F | THS 2.2 | Unit | ||||
|---|---|---|---|---|---|---|---|
| Identification | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | 35% RH / 30 | 60% RH / 22 | 75% RH / 30 | |
| ISO parameters and product-specific constituents | |||||||
| Glycerol | 4.56 ± 0.38 | 4.13 ± 0.38 | 3.17 ± 0.21 | 6.43 ± 0.30 | 7.09 ± 0.44 | 6.30 ± 0.25 | [μg/mL] |
| Nicotine | 4.02 ± 0.31 | 3.32 ± 0.25 | 1.97 ± 0.15 | 2.21 ± 0.06 | 2.15 ± 0.07 | 1.87 ± 0.09 | [μg/mL] |
| NFDPM | 61.8 ± 2.4 | 54.3 ± 2.2 | 53.8 ± 3.9 | 17.1 ± 1.7 | 18.5 ± 1.4 | 19.1 ± 1.9 | [μg/mL] |
| Carbon monoxide | 53.8 ± 2.7 | 53.0 ± 0.8 | 44.4 ± 2.0 | 0.69 ± 0.06 | 0.93 ± 0.02 | 0.71 ± 0.03 | [μg/mL] |
| Ammonia | 71.2 ± 4.7 | 49.9 ± 3.2 | 38.8 ± 2.9 | 18.9 ± 0.6 | 15.9 ± 0.6 | 16.3 ± 1.0 | [ng/mL] |
| Carbonyls | |||||||
| Formaldehyde | 207.6 ± 25.8 | 114.1 ± 9.5 | 50.7 ± 3.9 | 7.10 ± 1.50 | 7.08 ± 0.67 | 6.25 ± 1.49 | [ng/mL] |
| Acetaldehyde | 3560 ± 200 | 2930 ± 110 | 2600 ± 150 | 287 ± 24 | 321 ± 30 | 363 ± 42 | [ng/mL] |
| Acetone | 1560 ± 100 | 1310 ± 60 | 1130 ± 70 | 55.1 ± 7.3 | 56.4 ± 5.8 | 63.2 ± 8.1 | [ng/mL] |
| Acrolein | 393 ± 19 | 327 ± 18 | 270 ± 18 | 14.0 ± 2.1 | 14.9 ± 2.2 | 20.1 ± 4.3 | [ng/mL] |
| Propionaldehyde | 277 ± 19 | 233 ± 11 | 209 ± 13 | 18.7 ± 2.2 | 21.1 ± 2.2 | 26.2 ± 3.4 | [ng/mL] |
| Crotonaldehyde | 106.8 ± 6.4 | 89.4 ± 5.5 | 76.2 ± 5.6 | 2.63 ± 0.35 | 2.74 ± 0.30 | 3.31 ± 0.59 | [ng/mL] |
| Methyl ethyl ketone | 420 ± 22 | 367 ± 22 | 317 ± 21 | 11.2 ± 1.5 | 12.1 ± 1.5 | 15.2 ± 2.2 | [ng/mL] |
| Butyraldehyde | 130.8 ± 7.8 | 109.3 ± 5.5 | 95.0 ± 6.7 | 19.7 ± 1.4 | 21.8 ± 1.8 | 23.0 ± 1.8 | [ng/mL] |
| Hydrogen cyanide | 998 ± 255 | 807 ± 67 | 720 ± 28 | 7.18 ± 0.51 | 4.68 ± 0.67 | 4.61 ± 0.27 | [ng/mL] |
| Mercury | 6.40 ± 0.46 | 7.23 ± 0.77 | 5.89 ± 0.71 | 3.67 ± 0.16 | 3.41 ± 0.09 | 3.65 ± 0.23 | [pg/mL] |
| Trace metals (except mercury) | |||||||
| Cadmium | 182 ± 14 | 176 ± 13 | 176 ± 11 | 0.19* | 0.25* | 0.31* | [pg/mL] |
| Lead | 51.0* | 43.5 ± 8.5 | 46.0 ± 2.5 | 1.43* | 0.74* | 1.77* | [pg/mL] |
| Chromium | 23.0* | 30.2* | 26.1* | 5.02* | 5.02* | 5.02* | [pg/mL] |
| Nickel | 25.0* | 32.8* | 19.5* | 24.1* | 24.1* | 24.1* | [pg/mL] |
| Arsenic | 15.9 ± 1.2 | 14.9 ± 1.4 | 13.5 ± 0.6 | 1.87* | 1.82* | 1.82* | [pg/mL] |
| Selenium | 8.55* | 7.64* | 6.67* | 0.91* | 1.08* | 1.26* | [pg/mL] |
| Nitrogen oxides | |||||||
| NO | 814 ± 60 | 820 ± 39 | 752 ± 64 | 24.7 ± 1.0 | 27.7 ± 1.5 | 27.6 ± 0.3 | [ng/mL] |
| NOx | 882 ± 59 | 901 ± 42 | 839 ± 77 | 26.2 ± 1.0 | 29.6 ± 1.8 | 28.9 ± 0.5 | [ng/mL] |
| Phenols and acid derivatives | |||||||
| Hydroquinone | 156 ± 8 | 147 ± 3 | 163 ± 4 | 8.25 ± 1.29 | 11.75 ± 0.84 | 13.14 ± 1.22 | [ng/mL] |
| Resorcinol | 3.48 ± 0.21 | 3.28 ± 0.09 | 3.26 ± 0.03 | 0.044 ± 0.006 | 0.058 ± 0.005 | 0.086 ± 0.012 | [ng/mL] |
| Catechol | 188 ± 12 | 157 ± 4 | 133 ± 3 | 17.8 ± 1.9 | 22.6 ± 1.2 | 23.6 ± 1.9 | [ng/mL] |
| Phenol | 40.25 ± 5.03 | 24.41 ± 2.41 | 5.73 ± 0.89 | 2.20 ± 0.49 | 2.28 ± 0.27 | 2.82 ± 0.18 | [ng/mL] |
| p-cresol | 24.06 ± 2.73 | 17.15 ± 1.38 | 6.07 ± 0.75 | 0.10 ± 0.02 | 0.11 ± 0.01 | 0.15 ± 0.01 | [ng/mL] |
| m-Cresol | 9.35 ± 1.04 | 6.67 ± 0.55 | 2.41 ± 0.26 | 0.050 ± 0.010 | 0.053 ± 0.006 | 0.070 ± 0.005 | [ng/mL] |
| o-Cresol | 12.17 ± 1.46 | 8.61 ± 0.79 | 3.28 ± 0.40 | 0.10 ± 0.02 | 0.12 ± 0.01 | 0.17 ± 0.02 | [ng/mL] |
| Acetamide | 24.1 ± 2.0 | 22.5 ± 1.1 | 14.9 ± 2.0 | 4.21 ± 0.39 | 4.86 ± 0.17 | 5.13 ± 0.25 | [ng/mL] |
| Acrylamide | 9.60 ± 0.94 | 7.74 ± 0.49 | 3.95 ± 0.58 | 2.38 ± 0.23 | 2.65 ± 0.14 | 2.55 ± 0.11 | [ng/mL] |
| Polycyclic aromatic hydrocarbons | |||||||
| Pyrene | 161 ± 8 | 139 ± 7 | 148 ± 15 | 11.02 ± 1.98 | 8.57 ± 0.75 | 8.87 ± 1.54 | [pg/mL] |
| Benzo[a]anthracene | 51.6 ± 1.4 | 46.0 ± 4.1 | 43.6 ± 3.7 | 2.29 ± 0.42 | 2.11 ± 0.12 | 2.10 ± 0.25 | [pg/mL] |
| Benzo[a]pyrene | 26.2 ± 1.0 | 22.1 ± 2.2 | 23.3 ± 2.3 | 1.55* | 1.52* | 1.52* | [pg/mL] |
| Dibenz[a,h]anthracene | 2.66 ± 0.19 | 2.45 ± 0.26 | 2.20 ± 0.26 | 0.15* | 0.15* | 0.15* | [pg/mL] |
| Volatiles | |||||||
| 1,3-Butadiene | 134 ± 4 | 109 ± 4 | 111 ± 4 | 0.38 ± 0.02 | 0.42 ± 0.04 | 0.48 ± 0.03 | [ng/mL] |
| Isoprene | 1690 ± 60 | 1470 ± 80 | 1450 ± 20 | 2.78 ± 0.22 | 3.32 ± 0.26 | 3.93 ± 0.31 | [ng/mL] |
| Acrylonitrile | 64.3 ± 1.6 | 56.8 ± 1.5 | 51.7 ± 2.6 | 0.27 ± 0.03 | 0.25 ± 0.04 | 0.29 ± 0.04 | [ng/mL] |
| Benzene | 206 ± 6 | 178 ± 5 | 169 ± 8 | 0.90 ± 0.04 | 0.91 ± 0.05 | 0.93 ± 0.04 | [ng/mL] |
| Toluene | 390 ± 13 | 347 ± 7 | 331 ± 20 | 2.80 ± 0.18 | 3.20 ± 0.24 | 3.41 ± 0.22 | [ng/mL] |
| Semi-volatiles | |||||||
| Pyridine | 74.9 ± 3.6 | 67.1 ± 1.5 | 54.9 ± 4.7 | 8.73 ± 0.51 | 11.32 ± 0.38 | 11.01 ± 0.34 | [ng/mL] |
| Quinoline | 1.07 ± 0.08 | 0.83 ± 0.03 | 0.50* | 0.020* | 0.020* | 0.020* | [ng/mL] |
| Styrene | 48.4 ± 2.0 | 45.0 ± 1.2 | 42.0 ± 2.8 | 0.94 ± 0.05 | 0.97 ± 0.04 | 1.05 ± 0.05 | [ng/mL] |
| Nitrobenzene | 0.90 ± 0.10 | 0.90 ± 0.08 | 0.37 ± 0.02 | 0.13 ± 0.01 | 0.20 ± 0.01 | 0.13 ± 0.01 | [ng/mL] |
| Epoxides and vinyl chloride | |||||||
| Vinyl chloride | 156 ± 9 | 142 ± 4 | 128 ± 6 | 5.65* | 5.65* | 5.65* | [pg/mL] |
| Ethylene oxide | 66.2 ± 3.2 | 61.6 ± 1.8 | 54.7 ± 3.1 | 0.41 ± 0.02 | 0.40 ± 0.02 | 0.54 ± 0.04 | [ng/mL] |
| Propylene oxide | 3.35 ± 0.08 | 2.82 ± 0.06 | 2.64 ± 0.16 | 0.20 ± 0.01 | 0.23 ± 0.01 | 0.24 ± 0.02 | [ng/mL] |
| Aromatic amines | |||||||
| 1-Aminonaphthalene | 34.7 ± 2.1 | 31.6 ± 1.6 | 29.6 ± 2.5 | 0.11* | 0.11* | 0.11* | [pg/mL] |
| 2-Aminonaphthalene | 21.8 ± 0.9 | 20.2 ± 1.5 | 22.7 ± 1.5 | 0.025* | 0.024* | 0.133* | [pg/mL] |
| 3-Aminobiphenyl | 6.94 ± 0.36 | 6.44 ± 0.45 | 7.29 ± 0.72 | 0.044* | 0.044* | 0.044* | [pg/mL] |
| 4-Aminobiphenyl | 5.26 ± 0.18 | 5.02 ± 0.28 | 5.80 ± 0.67 | 0.048 ± 0.020 | 0.071* | 0.111 ± 0.027 | [pg/mL] |
| o-Toluidine | 196 ± 34 | 160 ± 17 | 112 ± 5 | 0.98 ± 0.39 | 1.73 ± 0.14 | 0.94 ± 0.72 | [pg/mL] |
| Tobacco-specific nitrosamines | |||||||
| NNN | 635 ± 74 | 479 ± 24 | 363 ± 29 | 7.44 ± 0.46 | 8.15 ± 0.43 | 7.84 ± 0.46 | [pg/mL] |
| NAT | 645 ± 27 | 484 ± 32 | 375 ± 30 | 17.1 ± 1.4 | 18.0 ± 1.0 | 16.1 ± 0.7 | [pg/mL] |
| NAB | 79.3 ± 2.9 | 58.6 ± 4.5 | 46.5 ± 3.0 | 2.62 ± 0.19 | 2.65 ± 0.16 | 2.68 ± 0.14 | [pg/mL] |
| NNK | 550 ± 44 | 474 ± 45 | 355 ± 29 | 8.36 ± 0.84 | 8.94 ± 0.79 | 8.29 ± 0.50 | [pg/mL] |
[i] Abbreviations: NAB = N-nitrosoanabasine; NAT = N-nitrosoanatabine; NNK = 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone; NNN = N-nitrosonornicotine; NO = nitrogen oxide; NOx = nitrogen oxides; NFDPM = nicotine free dry particulate matter; SD = standard deviation For results <LOD, the values used in the calculation of mean and standard deviation were estimated by the LOD; for results <LOQ but >LOD, the values were estimated by the LOQ.