Robustness of HPHC Reduction for THS 2.2 Aerosol Compared with 3R4F Reference Cigarette Smoke Under High Intensity Puffing Conditions

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

doi:10.2478/cttr-2020-0008

Figures & Tables

Average reduction of HPHC concentrations (puff volume adjusted yields) in THS 2.2 aerosol as a percentage of concentration in 3R4F cigarette mainstream smoke. Comparison between various combinations of regimes and two levels of filter ventilation occlusion for 3R4F (i.e., 50% and 100%). The respective puffing conditions identified by A, E, H, L and N are described in Table 1 and Table 2. The number of HPHCs (n) considered for the calculation of the average reductions varied between the different combinations of conditions.

Average reduction of nicotine adjusted HPHC yields in THS 2.2 aerosol as a percentage of concentration in 3R4F cigarette mainstream smoke. Comparison between various combinations of regimes and two levels of filter ventilation occlusion for 3R4F (i.e., 50% and 100%). The respective puffing conditions identified by A, E, H, L and N are described in Table 1 and Table 2. The number of HPHCs (n) considered for the calculation of the average reductions varied between the different combinations of conditions.

HPHC reduction with 0.95 confidence interval (error bars) calculated for 3R4F filter ventilation occlusion of 50% (A) and 100% (B). The dashed lines indicate the lower limit of reduction defined for THS 2.2 under HCI and more intense regimes. Charts on the right hand side are individual means of aerosol/smoke concentrations determined for each product and condition. The respective puffing conditions identified by A, E, H, L and N are described in Table 1 and Table 2.

HPHCs categorized by threshold limit of robust reduction under HCI and more intense regimes and excluding ISO regime (THS 2_2 vs_ 3R4F 50% occlusion of filter ventilation)_

Compounds	n	Limit
1-Aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 4-aminobiphenyl, 1,3-butadiene, acrylonitrile, benzene, Cd, HCN, isoprene	10	≥ 99
CO, ethylene oxide, m-cresol, NNK, NNN, NO, NO_x, o-toluidine, p-cresol, vinyl chloride, quinoline, resorcinol, styrene, toluene	14	≥ 95
Acetone, acrolein, benzo[a]anthracene, benzo[a]pyrene, hydroquinone, MEK, NAB, NAT, o-cresol, Pb, pyrene	11	≥ 90
Crotonaldehyde, propionaldehyde	2	≥ 85
Acetaldehyde, As, catechol, dibenz[a,h]anthracene, formaldehyde	5	≥ 80
-	0	≥ 75
Butyraldehyde, pyridine	2	≥ 70
-	0	≥ 65
Acetamide, propylene oxide	2	≥ 60
Acrylamide, phenol	2	≥ 55
Ammonia	1	≥ 50
Hg	1	< 50

Mean (±stdev) of compound yields for each respective product and puffing intensity_For results < LOD, the values used in the calculation of mean and standard deviation were estimated by the LOD; for results LOD, the values were estimated by the LOQ_ An asterisk (*) indicates when more than two out of five replicate values were below LOQ and standard deviation is not reported_

Item	3R4F						THS 2.2

Regime	L^a		N		H		L	A	N	H	E

Blocked ventilation	50%	100%	50%	100%	50%	100%	NA
ISO parameters and product specific constituents
Glycerol (mg/item)	1.01 ± 0.05	1.12 ± 0.05	2.31 ± 0.08	2.37 ± 0.16	3.02 ± 0.09	3.32 ± 0.16	1.97 ± 0.14	5.86 ± 0.28	4.89 ± 0.35	6.02 ± 0.20	5.84 ± 0.40
Nicotine (mg/item)	0.76 ± 0.04	0.84 ± 0.02	1.67 ± 0.05	1.72 ± 0.06	2.14 ± 0.07	2.24 ± 0.07	0.39 ± 0.02	1.33 ± 0.04	1.08 ± 0.08	1.39 ± 0.07	1.65 ± 0.04
NFDPM (mg/item)^b	11.4 ± 0.6	13.4 ± 0.8	26.4 ± 1.2	30.6 ± 1.6	41.4 ± 3.0	52.1 ± 1.8	11.2 ± 0.4	31.0 ± 1.9	27.7 ± 1.0	27.4 ± 2.0	27.4 ± 2.4
Carbon monoxide (mg/item)	14.1 ± 0.5	17.1 ± 1.4	28.4 ± 0.9	30.3 ± 1.1	34.6 ± 1.3	40.2 ± 0.3	0.28 ± 0.05	0.58 ± 0.04	0.51 ± 0.04	0.50 ± 0.11	0.40 ± 0.08
Ammonia (μg/item)	9.58 ± 0.81	13.30 ± 0.91	24.33 ± 0.91	28.21 ± 2.19	42.39 ± 3.57	49.55 ± 5.52	1.76 ± 0.19	13.99 ± 0.76	10.37 ± 0.78	16.90 ± 0.98	21.97 ± 1.60
Carbonyls
Formaldehyde (μg/item)	26.4 ± 4.0	32.8 ± 2.2	84.2 ± 12.5	83.7 ± 9.2	116.6 ± 5.0	106.3 ± 11.0	4.68 ± 0.26	9.77 ± 0.73	8.79 ± 0.85	11.67 ± 2.52	17.09 ± 2.15
Acetaldehyde (μg/item)	694 ± 46	884 ± 44	1646 ± 96	1665 ± 73	2273 ± 47	2057 ± 229	138 ± 3	202± 6	201 ± 13	195 ± 17	183 ± 14
Acetone (μg/item)	286 ± 16	363 ± 20	655 ± 35	666 ± 31	906 ± 18	811 ± 87	18.0 ± 0.6	32.8 ± 1.4	31.4 ± 2.8	33.7 ± 4.0	33.6 ± 3.1
Acrolein (μg/item)	59.7 ± 5.1	73.8 ± 3.8	153.2 ± 11.7	156.7 ± 7.6	204.9 ± 5.3	190.4 ± 22.4	3.86 ± 0.25	9.01 ± 0.66	8.39 ± 0.88	9.93 ± 1.67	10.87 ± 1.38
Propionaldehyde (μg/item)	49.0 ± 2.9	62.1 ± 3.0	116.6 ± 7.2	118.8 ± 4.2	163.6 ± 3.6	147.3 ± 16.1	7.61 ± 0.29	12.43 ± 0.43	11.86 ± 0.91	12.37 ± 1.36	11.57 ± 1.03
Crotonaldehyde (μg/item)	13.7 ± 1.3	19.2 ± 1.9	48.0 ± 4.2	48.0 ± 2.5	74.5 ± 2.0	65.4 ± 7.8	0.99 ^*	3.29 ^*	3.29 ^*	3.32 ^*	3.33 ^*
Methyl ethyl ketone (μg/item)	72.7 ± 3.8	93.9 ± 5.9	178.1 ± 9.4	180.6 ± 8.3	255.0 ± 5.2	225.4 ± 22.9	4.89 ± 0.13	8.58 ± 0.56	7.78 ± 0.78	9.87 ± 0.97	9.70 ± 0.44
Butyraldehyde (μg/item)	34.3 ± 2.0	42.8 ± 2.0	79.0 ± 4.6	80.7 ± 2.4	112.7 ± 1.7	100.8 ± 11.3	13.1 ± 0.3	19.4 ± 1.2	18.3 ± 1.0	20.5 ± 1.2	18.9 ± 0.8
Hydrogen cyanide (μg/item)	128 ± 8	187 ± 7	323 ± 11	398 ± 20	419 ± 39	501 ± 33	1.75 ^*	2.52 ± 0.21	2.40 ± 0.26	3.16 ± 0.22	4.28 ± 0.64
Mercury (ng/item)	3.17 ± 0.22	3.25 ± 0.40	2.61 ± 0.09	4.44 ± 0.40	5.78 ± 0.35	6.03 ± 0.36	1.35 ± 0.13	1.88 ± 0.17	1.95 ± 0.15	1.80 ± 0.17	1.97 ± 0.13
Trace metals (except mercury)
Cadmium (ng/item)	36.9 ± 2.4	44.7 ± 5.0	97.1 ± 4.4	100.2 ± 5.8	102.2 ± 4.3	115.5 ± 2.3	0.090 ^*	0.090 ^*	0.128 ^*	0.090 ^*	0.090 ^*
Lead (ng/item)	25.7 ^*	25.7 ^*	25.8 ^*	26.0 ^*	28.4 ± 1.2	32.4 ± 1.2	0.94 ^*	0.72 ^*	0.49 ^*	0.94 ^*	0.94 ^*
Chromium (ng/item)	11.9 ^*	11.9 ^*	11.9 ^*	11.9 ^*	11.9 ^*	11.9 ^*	4.85 ^*	9.46 ^*	9.46 ^*	9.46 ^*	11.97 ^*
Nickel (ng/item)	12.9 ^*	12.9 ^*	18.9 ^*	12.9 ^*	12.9 ^*	12.9 ^*	15.9 ^*	15.9 ^*	15.9 ^*	15.9 ^*	15.9 ^*
Arsenic (ng/item)	7.49 ^*	7.49 ^*	7.55 ^*	8.35 ± 0.53	11.18 ± 0.29	11.82 ± 0.28	0.54 ^*	1.20^*	0.86 ^*	1.20 ^*	1.46 ± 0.24
Selenium (ng/item)	4.42 ^*	4.42 ^*	4.42 ^*	4.42 ^*	4.42 ^*	4.42 ^*	0.48 ^*	0.71 ^*	0.48 ^*	0.71 ^*	0.60 ^*
Nitrogen oxides
NO (μg/item)	240 ± 15	290 ± 13	470 ± 13	518 ± 23	664 ± 26	827 ± 114	7.63 ± 0.40	12.85 ± 1.80	10.55 ± 0.78	12.98 ± 1.30	12.20 ± 0.92
NO_x(μg/item)	257 ± 16	308 ± 13	506 ± 10	558 ± 22	720 ± 28	901 ± 121	8.19 ± 0.41	13.97 ± 1.90	11.40 ± 0.82	14.17 ± 1.31	14.94 ± 1.01
Semi-volatiles
Pyridine (μg/item)	11.4 ± 0.8	13.1 ± 1.8	29.1 ± 4.0	35.1 ± 5.8	47.7 ± 4.4	51.4 ± 2.4	1.99 ± 0.30	6.60 ± 0.53	6.11 ± 0.50	6.72 ± 0.80	4.77 ± 0.15
Quinoline (μg/item)	0.27 ± 0.02	0.29 ± 0.02	0.54 ± 0.04	0.51 ± 0.02	0.63 ± 0.05	0.64 ± 0.05	0.0030 ^*	0.0124 ± 0.0009	0.0110 ^*	0.0188 ± 0.0027	0.0252 ± 0.0014
Styrene (μg/item)	5.79 ± 0.84	6.99 ± 1.22	17.61 ± 4.52	18.36 ± 2.90	24.45 ± 3.22	24.16± 0.53	0.11 ± 0.00	0.52 ± 0.03	0.37 ± 0.04	0.57 ± 0.04	0.51 ± 0.03
Nitrobenzene (μg/item)	0.038 ^*	0.038 ^*	0.038 ^*	0.038 ^*	0.038 ^*	0.038 ^*	0.011 ^*	0.011 ^*	0.011 ^*	0.011 ^*	0.011 ^*
Phenols and acid derivatives
Hydroquinone (μg/item)	39.1 ± 4.0	41.2 ± 5.0	89.0 ± 2.1	97.5 ± 5.0	124.3 ± 6.6	138.2 ± 12.2	2.66 ± 0.20	8.67 ± 0.41	7.34 ± 0.64	8.11 ± 0.68	7.86 ± 0.64
Resorcinol (μg/item)	1.32 ^*	1.32 ^*	2.68 ± 0.17	2.20 ± 0.20	3.20 ± 0.37	3.84 ± 0.31	0.016 ^*	0.055 ^*	0.055 ^*	0.055 ^*	0.055 ^*
Catechol (μg/item)	42.1 ± 2.8	43.4 ± 5.2	94.1 ± 2.3	98.8 ± 7.0	120.5± 8.1	124.7 ± 9.4	5.10 ± 0.29	15.70 ± 0.75	14.57 ± 1.02	14.64 ± 1.23	12.42 ± 0.81
Phenol (μg/item)	8.13 ± 0.79	7.28 ± 1.06	17.96 ± 1.23	14.87 ± 1.66	16.96 ± 2.06	12.67 ± 0.82	0.099 ^*	2.111 ± 0.230	1.287 ± 0.199	4.219 ±0.374	8.960 ± 0.635
p-Cresol (μg/item)	5.11 ± 0.35	4.72 ± 0.58	10.59 ± 0.61	9.06 ± 1.01	11.04 ± 1.20	8.69 ± 0.57	0.010 ^*	0.083 ± 0.009	0.049 ± 0.006	0.161 ± 0.019	0.378 ± 0.024
m-Cresol (μg/item)	2.11 ± 0.21	1.99 ± 0.26	4.30 ± 0.26	3.75 ± 0.42	4.27 ± 0.48	3.44 ± 0.29	0.0060 ^*	0.0427 ± 0.0059	0.0231 ± 0.0026	0.0819 ± 0.0104	0.1966 ± 0.0116
o-Cresol (μg/item)	2.49 ± 0.27	2.26 ± 0.29	5.24 ± 0.33	4.39 ± 0.50	5.27 ± 0.65	4.26 ± 0.28	0.0080 ^*	0.0886 ± 0.0128	0.0552 ± 0.0074	0.1784 ± 0.0165	0.3606 ± 0.0213
Acetamide (μg/item)	4.53 ± 0.32	4.91 ± 0.28	12.81 ± 0.34	12.89 ± 0.36	15.62 ± 1.01	16.66 ± 2.04	0.96 ± 0.10	3.98 ± 0.24	3.33 ± 0.15	4.04± 0.34	5.23 ± 0.13
Acrylamide (μg/item)	1.68 ± 0.11	1.85 ± 0.14	4.68 ± 0.42	4.51 ± 0.32	4.86 ± 0.44	4.87 ± 0.51	0.46 ± 0.08	1.87 ± 0.08	1.42 ± 0.06	2.07 ± 0.09	2.58 ± 0.08
Polycyclic aromatic hydrocarbons
Pyrene (ng/item)	41.2 ± 2.0	47.4 ± 1.9	84.4 ± 5.5	91.0 ± 2.8	104.2 ±3.6	100.8 ± 3.4	3.25 ± 0.51	7.48 ± 0.44	6.11 ± 0.33	7.07 ± 0.78	5.49± 0.66
Benzo[a]anthracene (ng/item)	12.2 ± 0.4	14.3 ± 0.4	27.2 ± 2.1	29.6 ± 1.5	36.2 ± 1.2	35.9 ± 1.3	0.71 ± 0.10	1.93 ± 0.22	1.67 ± 0.09	2.07 ± 0.17	1.56 ± 0.15
Benzo[a]pyrene (ng/item)	6.10 ± 0.30	7.25 ± 0.15	13.21 ± 1.04	14.38 ± 0.61	15.63 ± 0.80	15.00 ± 0.74	0.35 ^*	0.70 ± 0.06	0.60 ± 0.07	0.80 ± 0.07	0.66 ± 0.08
Dibenz[a,h]anthracene (ng/item)	0.69 ^*	0.69 ^*	1.19 ± 0.15	1.18 ± 0.05	1.45 ± 0.06	1.60 ± 0.16	0.12 ^*	0.18 ^*	0.12 ^*	0.18 ^*	0.18 ^*
Volatiles
1,3-Butadiene (μg/item)	33.3 ± 3.1	41.5 ± 1.2	69.6 ± 6.5	96.7 ± 8.5	90.3 ± 2.8	104.6 ± 2.4	0.13 ± 0.02	0.15 ± 0.02	0.19 ± 0.07	0.16 ± 0.01	0.15 ± 0.01
Isoprene (μg/item)	381 ± 49	496 ± 19	835 ± 87	871 ± 77	1102 ± 32	1226± 56	1.27 ± 0.14	1.39 ± 0.16	1.96 ± 0.49	1.28 ± 0.12	1.35 ± 0.25
Acrylonitrile (μg/item)	7.87 ± 1.24	11.14 ± 0.17	22.72 ± 2.55	24.69± 2.25	31.68 ± 1.62	35.55 ± 2.58	0.11 ^*	0.11 ± 0.00	0.14 ± 0.02	0.12± 0.00	0.13 ± 0.02
Benzene (μg/item)	38.6 ± 5.3	48.9 ± 0.8	88.8 ± 6.9	90.4 ± 6.6	109.8 ± 5.4	113.3 ± 7.0	0.30 ± 0.01	0.53 ± 0.05	0.69 ± 0.11	0.56 ± 0.01	0.56 ± 0.09
Toluene (μg/item)	55.7 ± 12.9	68.6 ± 2.9	149.5 ± 10.9	158.8 ± 17.6	200.0 ± 15.9	200.8 ± 14.3	0.79 ± 0.07	1.60 ± 0.13	2.16 ± 0.46	1.74 ± 0.05	1.65 ± 0.36
Epoxides and vinyl chloride
Vinyl chloride (ng/item)	50.7 ± 4.1	54.8 ± 9.5	89.7 ± 11.4	107.6 ± 16.2	121.6 ± 8.5	136.2 ± 7.9	0.66 ^*	0.66 ^*	0.66 ^*	2.19 ^*	2.19 ^*
Ethylene oxide (μg/item)	9.43 ± 0.87	11.32 ± 0.95	18.18 ± 1.48	18.65 ± 0.84	24.09 ± 1.05	26.89 ± 1.23	0.16 ± 0.01	0.19 ± 0.02	0.20 ± 0.02	0.20 ± 0.01	0.23 ± 0.01
Propylene oxide (ng/item)	502 ± 56	527 ± 74	480 ± 39	1143 ± 239	1115± 121	1273 ± 153	89.9 ± 9.8	110.4 ± 12.1	137.3 ± 20.6	115.4 ± 12.5	99.3 ± 10.5
Aromatic amines
1-Aminonaphthalene (ng/item)	13.7 ± 1.2	13.5 ± 0.6	22.4 ± 2.2	22.3 ± 2.6	25.1 ± 1.6	23.5 ± 2.1	0.019 ^*	0.034 ± 0.003	0.039 ± 0.010	0.032± 0.005	0.031 ± 0.005
2-Aminonaphthalene (ng/item)	13.9 ± 2.4	10.9 ± 0.9	20.2 ± 2.3	17.4 ± 2.1	17.5 ± 1.7	18.7 ± 1.5	0.0120 ^*	0.0142 ^*	0.0145 ± 0.0024	0.0122 ^*	0.0072 ^*
3-Aminobiphenyl (ng/item)	2.82 ± 0.14	3.11 ± 0.28	4.67 ± 0.67	4.85 ± 0.51	5.55 ± 0.40	6.17 ± 0.24	0.0035 ^*	0.0056 ± 0.0017	0.0086 ± 0.0015	0.0051 ^*	0.0052 ± 0.0016
4-Aminobiphenyl (ng/item)	1.77 ± 0.09	2.09 ± 0.11	3.10 ± 0.47	3.10 ± 0.50	3.62 ± 0.35	3.70 ± 0.16	0.0056 ^*	0.0097 ± 0.0037	0.0128 ± 0.0036	0.0069 ± 0.0018	0.0084 ± 0.0018
o-Toluidine (ng/item)	59.6 ± 2.9	63.1 ± 2.8	118.7 ± 1.8	115.5 ± 3.5	127.2 ± 8.0	129.5 ± 2.4	0.35 ± 0.04	1.10 ± 0.10	1.12 ± 0.07	1.45 ± 0.09	2.15 ± 0.22
Tobacco-specific nitrosamines
NNN (ng/item)	123 ± 7	137 ± 7	252 ± 14	286 ± 17	357 ± 28	396 ± 22	2.50± 0.27	6.16 ± 0.87	5.61 ± 0.55	6.34 ± 0.23	6.58 ± 0.39
NAT (ng/item)	132 ± 3	133 ± 6	251 ± 29	279 ± 37	333 ± 14	398 ± 41	5.14± 0.61	14.42 ± 1.51	12.48 ± 1.35	14.04 ± 0.93	13.86 ± 0.79
NAB (ng/item)	12.1 ± 0.7	14.3 ± 1.2	27.9 ± 3.6	27.5 ± 3.0	29.9 ± 4.5	27.1 ± 1.5	0.97 ± 0.26	1.90 ± 0.22	1.49 ± 0.28	1.83 ± 0.22	1.82 ± 0.04
NNK (ng/item)	111 ± 5	115 ± 8	231 ± 10	245 ± 26	274 ± 14	324 ± 38	2.36± 0.33	6.17 ± 1.12	5.49 ± 0.58	6.28 ± 0.44	7.22 ± 0.71

Machine-smoking parameters used for generation of 3R4F mainstream smoke

Parameter (Unit)	Regime

	L(50)	L(100)	N(50)	N(100)	H(50)	H(100)
Puff volume (mL)	35	35	55	55	80	80
Puff interval (s)	60	60	30	30	25	25
Puff duration (s)	2.0	2.0	2.0	2.0	2.0	2.4
Occlusion (%)	50	100	50	100	50	100

HPHCs categorized by threshold limit of robust reduction over all regimes (THS 2_2 vs_ 3R4F 100% occlusion of filter ventilation)_

Compounds	n	Limit
1,3-Butadiene, 1-aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 4-aminobiphenyl, benzene, Cd, isoprene, o-toluidine	9	≥ 99
Acrylonitrile, CO, ethylene oxide, HCN, m-cresol, NNK, NNN, NO, NO_x, p-cresol, quinoline, resorcinol, styrene, toluene, vinyl chloride	15	≥ 95
Acetone, acrolein, benzo[a]anthracene, benzo[a]pyrene, crotonaldehyde, hydroquinone, MEK, NAT, o-cresol	9	≥ 90
NAB, Pb, pyrene	3	≥ 85
As, catechol	2	≥ 80
Formaldehyde, propionaldehyde, pyridine,	3	≥ 75
Acetaldehyde, dibenz[a,h]anthracene, propylene oxide	3	≥ 70
Acetamide	2	≥ 65
Acrylamide	1	≥ 60
Ammonia, phenol	2	≥ 55
-	0	≥ 50
Butyraldehyde, Hg	2	< 50

Mean (± stdev) of puff volume-adjusted compound yields for each respective product and puffing intensity_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_ An asterisk (*) indicates when more than two out of five replicate values were below LOQ and standard deviation is not reported_ (For explanations and abbreviations please refer to Table 6_)

Item	3R4F						THS 2.2

Regime	L		N		H		L	A	N	H	E

Blocked ventilation	50%	100%	50%	100%	50%	100%	NA
ISO parameters and product specific constituents
Glycerol (μg/mL)	3.32 ± 0.13	3.96 ± 0.17	3.49 ± 0.09	4.03 ± 0.19	3.55 ± 0.16	4.36 ± 0.19	9.36 ± 0.66	6.97 ± 0.34	7.41 ± 0.53	5.38 ± 0.18	3.79 ± 0.26
Nicotine (μg/mL)	2.48 ± 0.10	2.98 ± 0.07	2.51 ± 0.04	2.93 ± 0.06	2.52 ± 0.13	2.94 ± 0.04	1.85 ± 0.10	1.58 ± 0.05	1.64 ± 0.12	1.25 ± 0.06	1.07 ± 0.03
NFDPM (μg/mL)	37.3 ± 1.5	47.3 ± 2.5	39.8 ± 1.8	52.1 ± 2.0	48.8 ± 4.8	68.5 ± 2.6	53.3 ± 2.0	36.9 ± 2.2	42.0 ± 1.5	24.4 ± 1.7	17.8 ± 1.6
Carbon monoxide (μg/mL)	46.1 ± 2.0	60.6 ± 4.5	42.8 ± 1.2	51.6 ± 1.2	40.8 ± 2.8	52.9 ± 1.3	1.32 ± 0.24	0.69 ± 0.05	0.77 ± 0.06	0.44 ± 0.10	0.26 ± 0.05
Ammonia (ng/mL)	37.1 ± 3.3	51.4 ± 4.1	38.8 ± 1.2	45.1 ± 3.7	51.2 ± 3.5	68.1 ± 3.4	8.36 ± 0.89	16.66 ± 0.90	15.71 ± 1.17	15.09 ± 0.88	14.26 ± 1.04
Carbonyls
Formaldehyde (ng/mL)	84.8 ± 12.8	107.8 ± 8.4	137.0 ± 23.0	140.8 ± 14.8	145.8 ± 6.2	128.7 ± 19.4	22.3 ± 1.2	11.6 ± 0.9	13.3 ± 1.3	10.4 ± 2.2	11.1 ± 1.4
Acetaldehyde (ng/mL)	2230 ± 150	2900 ± 170	2680 ± 210	2800 ± 110	2840 ± 60	2490 ± 400	655 ± 14	241 ± 8	304 ± 19	175 ± 15	119 ± 9
Acetone (ng/mL)	918 ± 54	1194 ± 74	1065 ± 75	1120 ± 48	1132 ± 22	982 ± 154	85.9 ± 2.7	39.0 ± 1.7	47.6 ± 4.3	30.1 ± 3.6	21.8 ± 2.0
Acrolein (ng/mL)	192 ± 17	243 ± 15	249 ± 24	264 ± 11	256 ± 7	231 ± 39	18.40 ± 1.19	10.72 ± 0.78	12.72 ± 1.33	8.86 ± 1.49	7.06 ± 0.90
Propionaldehyde (ng/mL)	157 ± 10	204 ± 13	190 ± 15	200 ± 6	204 ± 4	178 ± 28	36.24 ± 1.40	14.80± 0.51	17.96 ± 1.38	11.05 ± 1.22	7.51 ± 0.67
Crotonaldehyde (ng/mL)	44.0 ± 4.9	63.2 ± 7.5	78.1 ± 8.1	80.7 ± 3.8	93.1 ± 2.5	79.3 ± 13.4	4.70^*	3.92^*	4.98^*	2.96^*	2.16^*
Methyl ethyl ketone (ng/mL)	234 ± 15	309 ± 26	289 ± 20	304 ± 13	319 ± 6	273 ± 42	23.30 ± 0.60	10.21 ± 0.67	11.79 ± 1.18	8.81 ± 0.87	6.30 ± 0.28
Butyraldehyde (ng/mL)	110 ± 7	141 ± 9	128 ± 10	136 ± 4	141 ± 2	122 ± 20	62.4 ± 1.5	23.1 ± 1.4	27.7 ± 1.5	18.3 ± 1.1	12.3 ± 0.5
Hydrogen cyanide (ng/mL)	457 ± 29	679 ± 23	516 ± 39	688 ± 26	526 ± 37	671 ± 57	8.33^*	3.00 ± 0.26	3.64 ± 0.40	2.82 ± 0.20	2.78 ± 0.42
Mercury (pg/mL)	11.04 ± 0.78	11.38 ± 1.42	4.41 ± 0.16	7.27 ± 0.85	6.37 ± 0.45	7.47 ±0.80	6.43 ± 0.60	2.24 ± 0.20	2.96 ± 0.22	1.60 ± 0.15	1.28 ± 0.08
Trace metals (except mercury)
Cadmium (pg/mL)	128 ± 9	161 ± 18	155 ± 5	172 ± 11	118 ± 4	144 ± 3	0.429^*	0.107^*	0.194^*	0.080^*	0.058^*
Lead (pg/mL)	89.2^*	92.6^*	41.3^*	44.4^*	32.9 ± 1.7	40.4 ± 2.1	4.49^*	0.85^*	0.74^*	0.84^*	0.61^*
Chromium (pg/mL)	41.3^*	42.9^*	19.0^*	20.4^*	13.8^*	14.8^*	23.09^*	11.26^*	14.34^*	8.45^*	7.77^*
Nickel (pg/mL)	44.8^*	46.5^*	30.4^*	22.1^*	14.9^*	16.1^*	75.7^*	18.9^*	24.1^*	14.2^*	10.3^*
Arsenic (pg/mL)	26.0^*	27.0^*	12.1^*	14.3 ± 1.0	12.9 ± 0.3	14.7 ± 0.4	2.59^*	1.43^*	1.31^*	1.07^*	0.95 ± 0.16
Selenium (pg/mL)	15.34^*	15.92^*	7.07^*	7.57^*	5.12^*	5.51^*	2.30^*	0.85^*	0.73^*	0.64^*	0.39^*
Nitrogen oxides
NO (ng/mL)	836 ± 36	1023 ± 63	738 ± 30	905 ± 50	728 ± 17	1072 ± 192	36.35 ± 1.89	15.29 ± 2.14	15.99 ± 1.17	11.59 ± 1.16	7.92 ± 0.60
NO_x(ng/mL)	896 ± 37	1089 ± 67	794 ± 33	974 ± 51	790 ± 18	1167 ± 205	39.00 ± 1.93	16.63 ± 2.26	17.27 ± 1.25	12.65 ± 1.17	9.70 ± 0.66
Semi-volatiles
Pyridine (ng/mL)	39.2 ± 3.9	47.4 ± 5.9	46.1 ± 7.0	60.6 ± 8.8	56.4 ± 5.3	70.6 ± 4.2	9.47 ± 1.43	7.85 ± 0.63	9.25 ± 0.75	6.00 ± 0.72	3.10 ± 0.10
Quinoline (ng/mL)	0.93 ± 0.05	1.06 ± 0.10	0.85 ± 0.08	0.89 ± 0.01	0.74 ± 0.07	0.88 ± 0.08	0.014^*	0.015 ± 0.001	0.017^*	0.017 ± 0.002	0.016 ± 0.001
Styrene (ng/mL)	19.8 ± 3.1	25.2 ± 3.6	28.0 ± 7.7	31.7 ± 4.5	28.9 ± 3.8	33.2 ± 2.1	0.54 ± 0.01	0.62 ± 0.03	0.57 ± 0.05	0.51 ± 0.03	0.33 ± 0.02
Nitrobenzene (ng/mL)	0.130^*	0.138^*	0.060^*	0.066^*	0.045^*	0.052^*	0.0524^*	0.0131^*	0.0167^*	0.0098^*	0.0071^*
Phenols and acid derivatives
Hydroquinone (ng/mL)	134 ± 8	148 ± 19	138 ± 7	164 ± 8	143 ± 9	174 ± 16	12.66 ± 0.96	10.32 ±0.49	11.11 ± 0.97	7.24 ± 0.61	5.11 ± 0.41
Resorcinol (ng/mL)	4.54^*	4.75^*	4.15 ± 0.34	3.71 ± 0.42	3.69 ± 0.48	4.83 ± 0.40	0.076^*	0.065^*	0.083^*	0.049^*	0.036^*
Catechol (ng/mL)	145 ± 6	156 ± 20	146 ± 6	166 ± 11	139 ± 9	157 ± 13	24.29 ± 1.38	18.69 ± 0.89	22.07 ± 1.55	13.07 ± 1.10	8.06 ± 0.52
Phenol (ng/mL)	27.9 ± 2.7	26.2 ± 4.0	27.8 ± 1.8	25.0 ± 2.7	19.5 ± 1.8	15.9 ± 1.2	0.47^*	2.51 ± 0.27	1.95 ± 0.30	3.77 ± 0.33	5.82 ± 0.41
p-Cresol (ng/mL)	17.6 ± 1.1	17.0 ± 2.3	16.4 ± 0.8	15.3 ± 1.6	12.7 ± 1.1	10.9 ± 0.8	0.048^*	0.098 ± 0.010	0.074 ± 0.009	0.144 ± 0.017	0.246 ± 0.016
m-Cresol (ng/mL)	7.24 ± 0.68	7.15 ± 0.99	6.67 ± 0.40	6.32 ± 0.63	4.92 ± 0.43	4.32 ± 0.39	0.029^*	0.051 ± 0.007	0.035 ± 0.004	0.073 ± 0.009	0.128 ± 0.008
o-Cresol (ng/mL)	8.53 ± 0.82	8.13 ± 1.13	8.12 ± 0.48	7.39 ± 0.76	6.06 ± 0.61	5.36 ± 0.39	0.038^*	0.106 ± 0.015	0.084 ± 0.011	0.159 ± 0.015	0.234 ± 0.014
Acetamide (ng/mL)	15.5 ± 0.8	17.8 ± 1.5	20.3 ± 0.8	22.3 ± 0.6	18.5 ± 1.5	22.8 ± 2.3	4.56 ± 0.48	4.74 ± 0.29	5.04 ± 0.23	3.61 ± 0.30	3.40 ± 0.09
Acrylamide (ng/mL)	5.75 ± 0.45	6.70 ± 0.59	7.41 ± 0.57	7.80 ± 0.47	5.74 ± 0.53	6.68 ± 0.72	2.17 ± 0.37	2.22 ± 0.09	2.15 ± 0.09	1.85 ± 0.08	1.67 ± 0.05
Polycyclic aromatic hydrocarbons
Pyrene (pg/mL)	143 ± 8	167 ± 8	139 ± 8	161 ± 8	120 ± 6	135 ± 3	15.49 ± 2.41	8.90 ± 0.52	9.25 ± 0.49	6.32 ± 0.69	3.57 ± 0.43
Benzo[a]anthracene (pg/mL)	42.2 ± 1.5	50.1 ± 1.3	44.9 ± 2.7	52.5 ± 3.0	41.6 ± 1.5	48.2 ± 1.8	3.37 ± 0.46	2.30 ± 0.26	2.53 ± 0.14	1.84 ± 0.15	1.01 ± 0.10
Benzo[a]pyrene (pg/mL)	21.2 ± 1.3	25.5 ± 0.9	21.7 ± 1.4	25.5 ± 1.4	18.0 ± 0.9	20.1 ± 1.1	1.69^*	0.84 ± 0.08	0.90 ± 0.10	0.71 ± 0.06	0.43 ± 0.05
Dibenz[a,h]anthracene (pg/mL)	2.39^*	2.42^*	1.97 ± 0.28	2.09 ± 0.10	1.66 ± 0.07	2.15 ± 0.20	0.59^*	0.22^*	0.19^*	0.16^*	0.12^*
Volatiles
1,3-Butadiene (ng/mL)	115 ± 11	143 ± 7	115 ± 10	170 ± 19	116 ± 4	150 ± 8	0.60 ± 0.09	0.18 ± 0.02	0.29 ± 0.10	0.14 ± 0.01	0.10 ± 0.01
Isoprene (ng/mL)	1310 ± 180	1710 ± 100	1380 ± 140	1530 ± 170	1410 ± 60	1760 ± 80	6.04 ± 0.66	1.65 ± 0.19	2.96 ± 0.74	1.14 ± 0.10	0.88 ± 0.16
Acrylonitrile (ng/mL)	27.1 ± 4.4	38.4 ± 1.0	37.5 ± 4.0	43.5 ± 4.7	40.6 ± 2.0	50.9 ± 3.8	0.510^*	0.130 ± 0.004	0.213 ± 0.029	0.103 ± 0.004	0.084 ± 0.014
Benzene (ng/mL)	133 ± 19	168 ± 6	147 ± 11	159 ± 15	141 ± 8	162 ± 9	1.44 ± 0.07	0.64 ± 0.05	1.05 ± 0.17	0.50 ± 0.01	0.36 ± 0.06
Toluene (ng/mL)	192 ± 45	236 ± 13	247 ± 17	279 ± 35	256 ± 22	287 ± 17	3.78 ± 0.32	1.91± 0.16	3.28 ± 0.70	1.56 ± 0.05	1.07 ± 0.23
Epoxides and vinyl chloride
Vinyl chloride (pg/mL)	175 ± 15	190 ± 37	148 ± 18	189 ± 29	156 ± 14	195 ± 13	3.13^*	0.78^*	1.00^*	1.96^*	1.42^*
Ethylene oxide (ng/mL)	32.5 ± 3.1	38.9 ± 2.4	30.0 ± 2.3	32.8 ± 2.3	30.9 ± 1.7	38.6 ± 3.5	0.75 ± 0.05	0.23 ± 0.02	0.31 ± 0.03	0.18 ± 0.00	0.15 ± 0.01
Propylene oxide (pg/mL)	1725 ± 188	1815 ± 249	793 ± 63	2008 ± 409	1428 ± 145	1817 ± 132	428.2± 46.7	131.4 ± 14.5	208.1 ± 31.2	103.0 ± 11.2	64.5 ± 6.8
Aromatic amines
1-Aminonaphthalene (pg/mL)	47.2 ± 3.9	46.6 ± 2.3	37.0 ± 3.5	38.2 ± 4.7	32.1 ± 2.5	33.6 ± 2.3	0.092^*	0.040 ± 0.003	0.059 ± 0.015	0.028 ± 0.005	0.020 ± 0.003
2-Aminonaphthalene (pg/mL)	47.9 ± 7.9	37.5 ± 2.3	33.3 ± 3.7	29.9 ± 3.9	22.4 ± 2.3	26.7 ± 1.3	0.0571^*	0.0169^*	0.0220 ± 0.0036	0.0109^*	0.0047^*
3-Aminobiphenyl (pg/mL)	9.71 ± 0.50	10.70 ± 0.70	7.72 ± 1.09	8.33 ± 0.89	7.11 ± 0.56	8.84 ± 0.48	0.0169^*	0.0066 ± 0.0021	0.0130 ± 0.0023	0.0046^*	0.0034 ± 0.0010
4-Aminobiphenyl (pg/mL)	6.09 ± 0.32	7.19 ± 0.38	5.12 ± 0.76	5.31 ± 0.78	4.64 ± 0.49	5.31 ± 0.31	0.0267^*	0.0115 ± 0.0045	0.0194 ± 0.0054	0.0062 ± 0.0016	0.0054 ±0.0012
o-Toluidine (pg/mL)	205 ± 10	217 ± 7	196 ± 2	198 ± 7	163 ± 11	185 ± 9	1.66 ± 0.17	1.30 ± 0.12	1.70 ± 0.10	1.29 ± 0.08	1.39 ± 0.14
Tobacco-specific nitrosamines
NNN (pg/mL)	423 ± 29	474 ± 33	418 ± 22	486 ± 33	438 ± 31	542 ± 17	11.91 ± 1.30	7.34 ± 1.04	8.50 ± 0.84	5.66 ± 0.20	4.27 ± 0.25
NAT (pg/mL)	451 ± 18	458 ± 31	416 ± 49	474 ± 64	409 ± 21	547 ± 78	24.50 ± 2.92	17.16 ± 1.80	18.92 ± 2.04	12.54 ± 0.83	9.00 ± 0.52
NAB (pg/mL)	41.6 ± 2.6	49.3 ± 4.3	46.2 ± 5.8	46.8 ± 5.4	36.7 ± 5.3	37.1 ± 2.2	4.63 ± 1.22	2.26 ± 0.26	2.26 ± 0.43	1.64 ± 0.19	1.18 ± 0.02
NNK (pg/mL)	379 ± 23	398 ± 32	384 ± 14	416 ± 45	336 ± 19	444 ± 56	11.23 ± 1.55	7.34 ± 1.33	8.32 ± 0.88	5.61 ± 0.39	4.69 ± 0.46

Machine-smoking parameters used for the generation of THS 2_2 aerosol

Parameter (Unit)	Regime

	Low L(ISO)	Normal N(HCI)	Augmented A	High H	Extreme E
Puff volume (mL)	35	55	60	80	110
Puff interval (s)	60	30	25	25	22
Puff duration (s)	2.0	2.0	2.4	2.4	4.5
Puff number (n)	6	12	14	14	14

Mean (± stdev) of nicotine-adjusted compound yields for each respective product and puffing intensity_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_ An asterisk (*) indicates when more than two out of five replicate values were below LOQ and standard deviation is not reported_ (For explanations and abbreviations please refer to Table 6_)

Item	3R4F						THS 2.2

Regime	L^a		N		H		L	A	N	H	E

Blocked ventilation	50%	100%	50%	100%	50%	100%	NA
ISO parameters and product specific constituents
Glycerol (mg/item/mg nicotine)	1.34 ± 0.07	1.33 ± 0.06	1.39 ± 0.05	1.37 ± 0.09	1.41 ± 0.04	1.48 ± 0.07	5.05 ± 0.36	4.42 ± 0.21	4.52 ± 0.32	4.32 ± 0.15	3.55 ± 0.25
Nicotine (mg/item/mg nicotine)	1.00 ± 0.05	1.00 ± 0.03	1.00 ± 0.03	1.00 ± 0.04	1.00 ± 0.03	1.00 ± 0.03	1.00 ± 0.06	1.00 ± 0.03	1.00 ± 0.07	1.00 ± 0.05	1.00 ± 0.03
NFDPM (mg/item/mg nicotine)^b	15.1 ± 0.8	15.9 ± 0.9	15.8 ± 0.7	17.8 ± 0.9	19.4 ± 1.4	23.3 ± 0.8	28.7 ± 1.1	23.4 ± 1.4	25.6 ± 0.9	19.6 ± 1.4	16.6 ± 1.5
Carbon monoxide (mg/item/mg nicotine)	18.6 ± 0.6	20.3 ± 1.6	17.0 ± 0.6	17.6 ± 0.6	16.2 ± 0.6	18.0 ± 0.1	0.71 ± 0.13	0.44 ± 0.03	0.47 ± 0.04	0.36 ± 0.08	0.24 ± 0.05
Ammonia (μg/item/mg nicotine)	12.7 ± 1.1	15.8 ± 1.1	14.6 ± 0.5	16.4 ± 1.3	19.8 ± 1.7	22.2 ± 2.5	4.51 ± 0.48	10.55 ± 0.57	9.57 ± 0.72	12.12 ± 0.71	13.33 ± 0.97
Carbonyls
Formaldehyde (μg/item/mg nicotine)	34.9 ± 5.3	38.9 ± 2.6	50.5 ± 7.5	48.6 ± 5.4	54.6 ± 2.3	47.5 ± 4.9	12.03 ± 0.67	7.37 ± 0.55	8.12 ± 0.78	8.37 ± 1.81	10.37 ± 1.30
Acetaldehyde (μg/item/mg nicotine)	917 ± 61	1050 ± 52	988 ± 58	967 ± 43	1064 ± 22	920 ± 102	354 ± 8	153 ±5	185 ± 12	140 ± 12	111 ± 9
Acetone (μg/item/mg nicotine)	378 ± 21	431 ± 23	393 ± 21	387 ± 18	424 ± 8	362 ± 39	46.4 ± 1.5	24.7 ±1.1	29.0 ± 2.6	24.2 ± 2.9	20.4 ± 1.9
Acrolein (μg/item/mg nicotine)	78.9 ± 6.7	87.6 ± 4.5	92.0 ± 7.0	91.0 ± 4.4	95.9 ± 2.5	85.1 ± 10.0	9.93 ± 0.64	6.79 ± 0.49	7.75 ± 0.81	7.12 ± 1.20	6.60 ± 0.84
Propionaldehyde (μg/item/mg nicotine)	64.8 ± 3.9	73.8 ± 3.5	70.0 ± 4.3	69.0 ± 2.4	76.6 ± 1.7	65.9 ± 7.2	19.56 ± 0.76	9.38 ± 0.32	10.94 ± 0.84	8.87 ± 0.98	7.02 ± 0.63
Crotonaldehyde (μg/item/mg nicotine)	18.1 ± 1.7	22.8 ± 2.2	28.8 ± 2.5	27.9 ± 1.5	34.9 ± 0.9	29.3 ± 3.5	2.54^*	2.48^*	3.04^*	2.38^*	2.02^*
Methyl ethyl ketone (μg/item/mg nicotine)	96.1 ± 5.0	111.5 ± 7.0	106.9 ± 5.7	104.9 ± 4.8	119.3 ± 2.4	100.8 ± 10.3	12.57 ± 0.32	6.47 ± 0.43	7.18 ± 0.72	7.08 ± 0.70	5.89 ± 0.27
Butyraldehyde (μg/item/mg nicotine)	45.3 ± 2.7	50.8 ± 2.4	47.4 ± 2.8	46.9 ± 1.4	52.7 ± 0.8	45.1 ± 5.0	33.7 ± 0.8	14.6 ± 0.9	16.9 ± 0.9	14.7 ± 0.9	11.5 ± 0.5
Hydrogen cyanide (μg/item/mg nicotine)	169 ± 10	222 ± 8	194 ± 6	231 ± 11	196 ± 18	224 ± 15	4.50^*	1.90 ± 0.16	2.22 ± 0.24	2.26 ± 0.16	2.60 ± 0.39
Mercury (ng/item/mg nicotine)	4.18 ± 0.30	3.86 ± 0.48	1.56 ± 0.05	2.58 ± 0.23	2.71 ± 0.16	2.69 ± 0.16	3.47 ± 0.33	1.42 ± 0.13	1.80 ± 0.14	1.29 ± 0.12	1.20 ± 0.08
Trace metals (except mercury)
Cadmium (ng/item/mg nicotine)	48.8 ± 3.2	53.1 ± 5.9	58.3 ± 2.7	58.2 ± 3.4	47.8 ± 2.0	51.6 ± 1.0	0.231^*	0.068^*	0.118^*	0.065^*	0.055^*
Lead (ng/item/mg nicotine)	34.0^*	30.5^*	15.5^*	15.1^*	13.3 ± 0.6	14.5 ± 0.6	2.42^*	0.54^*	0.45^*	0.68^*	0.57^*
Chromium (ng/item/mg nicotine)	15.72^*	14.13^*	7.14^*	6.91^*	5.57^*	5.32^*	12.46^*	7.14^*	8.73^*	6.78^*	7.27^*
Nickel (ng/item/mg nicotine)	17.05^*	15.32^*	11.37^*	7.49^*	6.04^*	5.77^*	40.86^*	11.99^*	14.68^*	11.40^*	9.65^*
Arsenic (ng/item/mg nicotine)	9.90^*	8.90^*	4.53^*	4.85 ± 0.31	5.24 ± 0.13	5.29 ± 0.12	1.40^*	0.90^*	0.80^*	0.86^*	0.89 ± 0.15
Selenium (ng/item/mg nicotine)	5.84^*	5.25^*	2.65^*	2.57^*	2.07^*	1.98^*	1.24^*	0.54^*	0.44^*	0.51^*	0.36^*
Nitrogen oxides
NO (μg/item/mg nicotine)	317 ± 20	344 ± 15	282 ± 8	301 ± 13	311 ± 12	370 ± 51	19.62 ± 1.02	9.69± 1.35	9.74 ± 0.72	9.31 ± 0.93	7.40 ± 0.56
NO_x(μg/item/mg nicotine)	340 ± 21	366 ± 16	304 ± 6	324 ± 13	337 ± 13	403 ± 54	21.05 ± 1.04	10.54 ± 1.43	10.52 ± 0.76	10.16 ± 0.94	9.07 ± 0.61
Semi-volatiles
Pyridine (μg/item/mg nicotine)	15.1 ± 1.1	15.5 ± 2.1	17.4 ± 2.4	20.4 ± 3.4	22.3 ± 2.0	23.0 ± 1.1	5.11 ± 0.77	4.98 ± 0.40	5.64 ± 0.46	4.82 ± 0.58	2.90 ± 0.09
Quinoline (μg/item/mg nicotine)	0.36 ± 0.02	0.35 ± 0.03	0.32 ± 0.03	0.30 ± 0.01	0.29 ± 0.02	0.29 ± 0.02	0.0077^*	0.0093 ± 0.0007	0.0102^*	0.0135 ± 0.0020	0.0153 ± 0.0008
Styrene (μg/item/mg nicotine)	7.65 ± 1.11	8.30 ± 1.44	10.57 ± 2.71 10.66 ± 1.69		11.44 ± 1.51	10.80± 0.24	0.29 ± 0.01	0.39 ± 0.02	0.34 ± 0.03	0.41 ± 0.03	0.31 ± 0.02
Nitrobenzene (μg/item/mg nicotine)	0.050^*	0.045^*	0.023^*	0.022^*	0.018^*	0.017^*	0.0283^*	0.0083^*	0.0102^*	0.0079^*	0.0067^*
Phenols and acid derivatives
Hydroquinone (μg/item/mg nicotine)	51.6 ± 5.2	48.9 ± 5.9	53.4 ± 1.3	56.6 ± 2.9	58.2 ± 3.1	61.8 ± 5.4	6.83 ± 0.52	6.54 ± 0.31	6.77 ± 0.59	5.81 ± 0.49	4.77 ± 0.39
Resorcinol (μg/item/mg nicotine)	1.74^*	1.57^*	1.61 ± 0.10	1.28 ± 0.12	1.50 ± 0.17	1.72 ± 0.14	0.041^*	0.041^*	0.051^*	0.039^*	0.033^*
Catechol (μg/item/mg nicotine)	55.6 ± 3.7	51.6 ± 6.2	56.5 ± 1.4	57.4 ± 4.0	56.4 ± 3.8	55.8 ± 4.2	13.11 ± 0.74	11.84 ± 0.57	13.44 ± 0.94	10.49 ± 0.88	7.54 ± 0.49
Phenol (μg/item/mg nicotine)	10.75 ± 1.04	8.65 ± 1.26	10.78 ± 0.74	8.64 ± 0.97	7.94 ± 0.96	5.66 ± 0.37	0.25^*	1.59 ± 0.17	1.19 ± 0.18	3.02 ± 0.27	5.44 ± 0.39
p-Cresol (μg/item/mg nicotine)	6.76 ± 0.46	5.61 ± 0.69	6.36 ± 0.37	5.26 ± 0.58	5.17 ± 0.56	3.88 ± 0.25	0.026^*	0.062 ± 0.007	0.045 ± 0.005	0.115 ± 0.014	0.230 ± 0.015
m-Cresol (μg/item/mg nicotine)	2.78 ± 0.28	2.36 ± 0.30	2.58 ± 0.16	2.18 ± 0.24	2.00 ± 0.23	1.54 ± 0.13	0.015^*	0.032 ± 0.004	0.021 ± 0.002	0.059 ± 0.007	0.119 ± 0.007
o-Cresol (μg/item/mg nicotine)	3.28 ± 0.36	2.68 ± 0.34	3.14 ± 0.20	2.55 ± 0.29	2.47 ± 0.31	1.91 ± 0.13	0.021^*	0.067 ± 0.010	0.051 ± 0.007	0.128 ± 0.012	0.219 ± 0.013
Acetamide (μg/item/mg nicotine)	5.99 ± 0.42	5.83 ± 0.33	7.69 ± 0.21	7.49 ± 0.21	7.31 ± 0.47	7.45 ± 0.91	2.46 ± 0.26	3.00 ± 0.18	3.07 ± 0.14	2.90 ± 0.24	3.18 ± 0.08
Acrylamide (μg/item/mg nicotine)	2.22 ± 0.15	2.19 ± 0.16	2.81 ± 0.25	2.62 ± 0.18	2.28 ± 0.21	2.18 ± 0.23	1.17 ± 0.20	1.41 ± 0.06	1.31 ±0.06	1.49 ± 0.06	1.56 ± 0.05
Polycyclic aromatic hydrocarbons
Pyrene (ng/item/mg nicotine)	54.4 ± 2.7	56.3 ± 2.3	50.7 ± 3.3	52.8 ± 1.6	48.8 ± 1.7	45.1 ± 1.5	8.36 ± 1.30	5.64 ± 0.33	5.64 ± 0.30	5.07 ± 0.56	3.33 ± 0.40
Benzo[a]anthracene (ng/item/mg nicotine)	16.1 ± 0.5	16.9 ± 0.5	16.4 ± 1.3	17.2 ± 0.9	16.9 ± 0.6	16.0 ± 0.6	1.82 ± 0.25	1.46 ± 0.16	1.54 ± 0.08	1.48 ± 0.12	0.95 ± 0.09
Benzo[a]pyrene (ng/item/mg nicotine)	8.06 ± 0.39	8.60 ± 0.18	7.93 ± 0.62	8.35 ± 0.35	7.32 ± 0.38	6.70 ± 0.33	0.91^*	0.53 ± 0.05	0.55 ± 0.06	0.57± 0.05	0.40 ± 0.05
Dibenz[a,h]anthracene (ng/item/mg nicotine)	0.91^*	0.82^*	0.72 ± 0.09	0.69 ± 0.03	0.68 ± 0.03	0.72 ± 0.07	0.32^*	0.14^*	0.11^*	0.13^*	0.11^*
Volatiles
1,3-Butadiene (μg/item/mg nicotine)	44.06 ± 4.11	49.32 ± 1.44	41.77 ± 3.91	56.18 ± 4.96	42.29 ± 1.30	46.78 ± 1.07	0.323 ± 0.048	0.114 ± 0.016	0.174 ± 0.061	0.112 ± 0.010	0.094 ± 0.008
Isoprene (μg/item/mg nicotine)	504 ± 65	589 ± 23	501 ± 52	506 ± 44	516 ± 15	548 ± 25	3.26 ± 0.36	1.05 ± 0.12	1.81 ± 0.45	0.92 ± 0.08	0.82± 0.15
Acrylonitrile (μg/item/mg nicotine)	10.4 ± 1.6	13.2 ± 0.2	13.6 ± 1.5	14.3 ± 1.3	14.8 ± 0.8	15.9 ± 1.2	0.275^*	0.082 ± 0.002	0.130 ± 0.017	0.083 ± 0.003	0.078 ± 0.013
Benzene (μg/item/mg nicotine)	51.1 ± 7.0	58.0 ± 0.9	53.3 ± 4.2	52.5± 3.9	51.4 ± 2.5	50.6 ± 3.1	0.78 ± 0.04	0.40 ± 0.03	0.64 ± 0.10	0.40± 0.01	0.34 ± 0.06
Toluene (μg/item/mg nicotine)	73.6 ± 17.1	81.5 ± 3.4	89.8 ± 6.6	92.2 ± 10.2	93.6 ± 7.4	89.8 ± 6.4	2.04 ± 0.17	1.21 ± 0.10	2.00 ± 0.42	1.25 ± 0.04	1.00 ± 0.22
Epoxides and vinyl chloride
Vinyl chloride (ng/item/mg nicotine)	67.0 ± 5.5	65.1 ± 11.2	53.9 ±6.8	62.5 ± 9.4	56.9 ± 4.0	60.9 ± 3.6	1.69^*	0.50^*	0.61^*	1.57^*	1.33^*
Ethylene oxide (μg/item/mg nicotine)	12.5 ± 1.1	13.4 ± 1.1	10.9 ± 0.9	10.8 ± 0.5	11.3 ± 0.5	12.0 ± 0.5	0.41 ± 0.03	0.15 ± 0.01	0.19 ± 0.02	0.15 ± 0.00	0.14 ± 0.01
Propylene oxide (ng/item/mg nicotine)	663 ± 73	626 ± 88	288 ± 23	664 ± 139	522 ± 57	569 ± 69	231.1 ± 25.2	83.2 ± 9.2	126.8 ± 19.0	82.7 ±9.0	60.3 ± 6.4
Aromatic amines
1-Aminonaphthalene (ng/item/mg nicotine)	18.2 ± 1.6	16.1 ± 0.7	13.4 ± 1.3	12.9 ± 1.5	11.7 ± 0.7	10.5 ± 0.9	0.050^*	0.026 ± 0.002	0.036 ±0.009	0.023 ± 0.004	0.019 ± 0.003
2-Aminonaphthalene (ng/item/mg nicotine)	18.42 ± 3.11	12.94 ± 1.12	12.10 ± 1.39	10.12 ± 1.20	8.19 ± 0.78	8.34 ± 0.69	0.0308^*	0.0107^*	0.0134 ± 0.0022	0.0087^*	0.0044^*
3-Aminobiphenyl (ng/item/mg nicotine)	3.73 ± 0.19	3.70 ± 0.33	2.81± 0.40	2.82 ± 0.30	2.60 ± 0.19	2.76 ± 0.11	0.0091^*	0.0042 ± 0.0013	0.0079 ± 0.0014	0.0037^*	0.0032 ± 0.0010
4-Aminobiphenyl (ng/item/mg nicotine)	2.34 ± 0.12	2.48 ± 0.13	1.86± 0.28	1.80 ± 0.29	1.70 ± 0.17	1.66 ± 0.07	0.0144^*	0.0073 ± 0.0028	0.0118 ± 0.0033	0.0050 ± 0.0013	0.0051 ± 0.0011
o-Toluidine (ng/item/mg nicotine)	78.8 ± 3.8	75.0 ± 3.3	71.2 ± 1.1	67.1 ± 2.0	59.5 ± 3.8	57.9 ± 1.1	0.90 ± 0.09	0.83 ± 0.08	1.03 ± 0.06	1.04 ± 0.06	1.30 ± 0.14
Tobacco-specific nitrosamines
NNN (ng/item/mg nicotine)	163 ± 9	163 ± 8	151 ± 9	166 ± 10	167 ± 13	177 ± 10	6.43 ± 0.70	4.65 ± 0.66	5.18 ± 0.51	4.54 ± 0.16	3.99 ± 0.24
NAT (ng/item/mg nicotine)	174 ± 4	157 ± 7	151 ± 17	162 ± 22	156 ± 7	178 ± 18	13.22 ± 1.58	10.87 ± 1.14	11.52 ± 1.24	10.07 ± 0.67	8.42 ± 0.48
NAB (ng/item/mg nicotine)	16.1 ± 1.0	16.9 ± 1.4	16.7 ± 2.1	16.0 ± 1.7	14.0 ± 2.1	12.1 ± 0.7	2.50 ± 0.66	1.43 ± 0.16	1.37 ± 0.26	1.32 ± 0.16	1.11 ± 0.02
NNK (ng/item/mg nicotine)	146 ± 6	137 ± 10	139 ± 6	142 ± 15	128 ± 7	145 ± 17	6.06 ± 0.84	4.65 ± 0.84	5.07 ± 0.53	4.50 ± 0.31	4.38 ± 0.43

HPHCs categorized by threshold limit of robust reduction under HCI and more intense regimes and excluding ISO regime (THS 2_2 vs_ 3R4F 100% occlusion of filter ventilation)_

Compounds	n	Limit
1-Aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 4-aminobiphenyl, 1,3-butadiene, acrylonitrile, benzene, Cd, HCN, isoprene, o-toluidine	11	≥ 99
Benzo[a]pyrene, CO, ethylene oxide, m-cresol MEK, NAT, NNK, NNN, NO, NO_x, Pb, p-cresol, quinoline, resorcinol, styrene, toluene, vinyl chloride	17	≥ 95
Acetone, acrolein, As, benzo[a]anthracene, crotonaldehyde, hydroquinone, NAB, o-cresol, pyrene	9	≥ 90
Acetaldehyde, dibenz[a,h]anthracene, formaldehyde, propionaldehyde, propylene oxide	5	≥ 85
Catechol	1	≥ 80
Butyraldehyde, pyridine	2	≥ 75
-	0	≥ 70
Acetamide	1	≥ 65
Acrylamide	1	≥ 60
Ammonia, phenol	2	≥ 55
Hg	1	≥ 50

Robustness of HPHC Reduction for THS 2.2 Aerosol Compared with 3R4F Reference Cigarette Smoke Under High Intensity Puffing Conditions

Figures & Tables

Figure 1

Figure 2

Figure 3

HPHCs categorized by threshold limit of robust reduction under HCI and more intense regimes and excluding ISO regime (THS 2_2 vs_ 3R4F 50% occlusion of filter ventilation)_

Machine-smoking parameters used for generation of 3R4F mainstream smoke

HPHCs categorized by threshold limit of robust reduction over all regimes (THS 2_2 vs_ 3R4F 100% occlusion of filter ventilation)_

Machine-smoking parameters used for the generation of THS 2_2 aerosol

HPHCs categorized by threshold limit of robust reduction under HCI and more intense regimes and excluding ISO regime (THS 2_2 vs_ 3R4F 100% occlusion of filter ventilation)_

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