Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

Laurent Poget; Catherine Goujon; Samuel Kleinhans; Serge Maeder; Jean-Pierre Schaller

doi:10.2478/cttr-2021-0008

Figures & Tables

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%).

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.

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.

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.

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]
NO_x	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]

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 lowest^a 3R4F ISO cond. (Threshold)	Lowest^b 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

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, NO_x, 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

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]
NO_x	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]

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]
NO_x	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]

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

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, NO_x, 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

Ambient conditions representing the climatic zones considered for the study_

Conditions (abbreviation)	Temperature (°C)	Relative humidity (% RH)
ISO^a (S)	22 ± 2	60 ± 5
Hot and Very Humid (H)	30 ± 2	75 ± 5
Hot and Dry (D)	30 ± 2	35 ± 5

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)

Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

Figures & Tables

Figure 1

Figure 2

Figure 3

Figure 4

Mean (± SD) of nicotine-adjusted yields of compounds investigated in 3R4F mainstream smoke and THS 2_2 aerosol, measured under various climatic conditions_

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_

HPHCs categorized by thresholds of robust reduction: THS 2_2 vs_ 3R4F over all climatic conditions_

Mean (± SD) of compound deliveries investigated in 3R4F mainstream smoke and THS 2_2 aerosol, measured under various climatic conditions_

Mean (± SD) of volume-adjusted yields of compounds investigated in 3R4F mainstream smoke and THS 2_2 aerosol, measured under various climatic conditions_

Mean differences (CI95%) of volume-adjusted yields in “Hot and Very Humid” relative to ISO climatic conditions_

HPHCs categorized by thresholds of robust reduction: THS 2_2 over all climatic conditions vs_ 3R4F ISO climatic conditions_

Ambient conditions representing the climatic zones considered for the study_

Puff count for 3R4F as function of climatic conditions_

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