An 8-Month Systems Toxicology Inhalation/Cessation Study in Apoe−/− Mice to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared With Conventional Cigarettes

doi: 10.1093/toxsci/kfv243

Toxicological Sciences 149(2),411–432, 2016

Upon further review of Supplementary Table 1, the authors identified that some data were erroneously swapped when reporting. The corrected table is available online.

This error has no impact on the overall validity or conclusion of the study.

The authors regret this error.

Supplementary Table 1. Yields per cigarette of selected 3R4F mainstream smoke and THS aerosol constituents (HPHCs).

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A. Normalized for nicotine levels, analysis from a THS2.2 batch used in this study (3R4F was measured in a previous study but is considered representative of the actual batches used during this study).

ISO parameters		THS2.2	3R4F
1. Carbon monoxide	mg/mg nicotine	0.437 ± 0.031	14.8 ± 0.715
2. Nicotine	mg/mg nicotine	1 ± 0.045	1 ± 0.0542
3. Tar	mg/mg nicotine	6.304 ± 1.214	14.3 ± 0.717
4. TPM	mg/mg nicotine	34.72 ± 1.396	22.2 ± 1.2
5. Water	mg/mg nicotine	27.41 ± 1.937	7.01 ± 0.673
*Aliphatic dienes*
6. 1,3-Butadiene	µg/mg nicotine	0.298 ± 0.053	36.7 ± 3.6
7. Isoprene	µg/mg nicotine	2.483 ± 0.335	427 ± 36.4
*Carbonyls*
8. Acetaldehyde	µg/mg nicotine	157.9 ± 15.78	719 ± 50.1
9. Acetone	µg/mg nicotine	29.35 ± 3.463	323 ± 11.9
10. Acrolein	µg/mg nicotine	8.165 ± 1.189	77 ± 5.51
11. Butyraldehyde	µg/mg nicotine	20.32 ± 2.024	41.7 ± 3.64
12. Crotonaldehyde	µg/mg nicotine	2.809 ± 0.333	40.5 ± 4.31
13. Formaldehyde	µg/mg nicotine	2.623 ± 0.271	28.3 ± 3.48
14. Methyl ethyl ketone	µg/mg nicotine	5.986 ± 0.91	91.9 ± 5.79
15. Propionaldehyde	µg/mg nicotine	11.75 ± 1.483	58.1 ± 2.68
*Acid derivatives*
16. Acetamide	µg/mg nicotine	3.063 ± 0.283	7.17 ± 0.399
17. Acrylamide	µg/mg nicotine	1.918 ± 0.188	2.03 ± 0.157
18. Acrylonitrile	µg/mg nicotine	0.166 ± 0.013	14.4 ± 0.894
*Epoxides*
19. Ethylene oxide	µg/mg nicotine	0.167 ± 0.011	12.9 ± 0.998
20. Propylene oxide	µg/mg nicotine	0.094 ± 0.008	0.723 ± 0.0234
*Nitro compounds*
21. Nitrobenzene		N.D.	N.D.
*Aromatic Amines*
22. 1-Aminonaphthalene	ng/mg nicotine	0.065 ± 0.007	9.95 ± 0.6
23. 2-Aminonaphthalene	ng/mg nicotine	3/4 < 0.024	5.11 ± 0.186
24. 3-Aminobiphenyl	ng/mg nicotine	0.043 ± 0.005	1.64 ± 0.213
25. 4-Aminobiphenyl	ng/mg nicotine	4/4 < 0.032	1.31 ± 0.115
26. o-Toluidine	ng/mg nicotine	0.962 ± 0.076	43.5 ± 1.45
27. Benzidine	ng/mg nicotine	4/4 < 7E-4	N.D.
*N-Heterocyclic aromatics*
28. Pyridine	µg/mg nicotine	6.343 ± 0.283	18 ± 0.833
29. Quinoline	µg/mg nicotine	0.016 ± 0.001	0.273 ± 0.0276
*Halogen compounds*
30. Vinyl chloride	ng/mg nicotine	4/4 < 2.477	50.2 ± 2.75
*Inorganic compounds*
31. Ammonia	µg/mg nicotine	10.18 ± 0.611	19.4 ± 0.847
32. Hydrogen cyanide	µg/mg nicotine	2.905 ± 0.201	215 ± 17.2
33. Nitric oxide	µg/mg nicotine	11.37 ± 0.521	218 ± 10.3
34. Nitrogen oxides	µg/mg nicotine	11.48 ± 0.516	240 ± 12.3
*Monocyclic aromatics*
35. Benzene	µg/mg nicotine	0.538 ± 0.037	46.8 ± 1.7
36. Styrene	µg/mg nicotine	0.578 ± 0.048	11.9 ± 0.497
37. Toluene	µg/mg nicotine	2.172 ± 0.231	97.8 ± 3.8
*N-nitrosamines*
38. N-Nitrosoanabasine (NAB)	ng/mg nicotine	4/4 < 2.173	18 ± 1.24
39. N-Nitrosoanatabine (NAT)	ng/mg nicotine	11.67 ± 1.224	173 ± 10.1
40. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)	ng/mg nicotine	4.631 ± 0.387	117 ± 5.56
41. N-Nitrosonornicotine (NNN)	ng/mg nicotine	10.37 ± 1.039	155 ± 4.31
*Phenols*
42. Catechol	µg/mg nicotine	15.53 ± 1.698	43.8 ± 2.17
43. m+p-cresol	µg/mg nicotine	0.123 ± 0.02	6.04 ± 0.448
44. o-cresol	µg/mg nicotine	0.102 ± 0.014	2.08 ± 0.18
45. Hydroquinone	µg/mg nicotine	6.614 ± 0.859	40.2 ± 1.85
46. Phenol	µg/mg nicotine	1.617 ± 0.269	6.59 ± 0.497
47. Resorcinol	µg/mg nicotine	0.049 ± 0.004	0.894 ± 0.0364
*PAHs*
48. Benzo[a]pyrene	ng/mg nicotine	3/4 < 0.696	4.66 ± 1.87
49. Benz[a]anthracene	ng/mg nicotine	1.078 ± 0.051	9.21 ± 3.19
50. Dibenz[a,h]anthracene	ng/mg nicotine	4/4 < 0.07	3/8 < 0
51. Pyrene	ng/mg nicotine	4.085 ± 0.24	25.5 ± 15.2
*Metals/Elements*
52. Arsenic	ng/mg nicotine	3/3 < 0.787	3.32 ± 0.209
53. Cadmium	ng/mg nicotine	0.371 ± 0.008	63.7 ± 3.28
54. Chromium	ng/mg nicotine	3/3 < 0.118	4/4 < 0.257
55. Lead	ng/mg nicotine	3/3 < 2.332	14.8 ± 0.773
56. Mercury	ng/mg nicotine	1.024 ± 0.105	1.86 ± 0.0981
57. Nickel	ng/mg nicotine	2/3 < 0.118	4/4 < 0.257
58. Selenium	ng/mg nicotine	3/3 < 0.383	0.687 ± 0.126

ISO parameters		THS2.2	3R4F
1. Carbon monoxide	mg/mg nicotine	0.437 ± 0.031	14.8 ± 0.715
2. Nicotine	mg/mg nicotine	1 ± 0.045	1 ± 0.0542
3. Tar	mg/mg nicotine	6.304 ± 1.214	14.3 ± 0.717
4. TPM	mg/mg nicotine	34.72 ± 1.396	22.2 ± 1.2
5. Water	mg/mg nicotine	27.41 ± 1.937	7.01 ± 0.673
*Aliphatic dienes*
6. 1,3-Butadiene	µg/mg nicotine	0.298 ± 0.053	36.7 ± 3.6
7. Isoprene	µg/mg nicotine	2.483 ± 0.335	427 ± 36.4
*Carbonyls*
8. Acetaldehyde	µg/mg nicotine	157.9 ± 15.78	719 ± 50.1
9. Acetone	µg/mg nicotine	29.35 ± 3.463	323 ± 11.9
10. Acrolein	µg/mg nicotine	8.165 ± 1.189	77 ± 5.51
11. Butyraldehyde	µg/mg nicotine	20.32 ± 2.024	41.7 ± 3.64
12. Crotonaldehyde	µg/mg nicotine	2.809 ± 0.333	40.5 ± 4.31
13. Formaldehyde	µg/mg nicotine	2.623 ± 0.271	28.3 ± 3.48
14. Methyl ethyl ketone	µg/mg nicotine	5.986 ± 0.91	91.9 ± 5.79
15. Propionaldehyde	µg/mg nicotine	11.75 ± 1.483	58.1 ± 2.68
*Acid derivatives*
16. Acetamide	µg/mg nicotine	3.063 ± 0.283	7.17 ± 0.399
17. Acrylamide	µg/mg nicotine	1.918 ± 0.188	2.03 ± 0.157
18. Acrylonitrile	µg/mg nicotine	0.166 ± 0.013	14.4 ± 0.894
*Epoxides*
19. Ethylene oxide	µg/mg nicotine	0.167 ± 0.011	12.9 ± 0.998
20. Propylene oxide	µg/mg nicotine	0.094 ± 0.008	0.723 ± 0.0234
*Nitro compounds*
21. Nitrobenzene		N.D.	N.D.
*Aromatic Amines*
22. 1-Aminonaphthalene	ng/mg nicotine	0.065 ± 0.007	9.95 ± 0.6
23. 2-Aminonaphthalene	ng/mg nicotine	3/4 < 0.024	5.11 ± 0.186
24. 3-Aminobiphenyl	ng/mg nicotine	0.043 ± 0.005	1.64 ± 0.213
25. 4-Aminobiphenyl	ng/mg nicotine	4/4 < 0.032	1.31 ± 0.115
26. o-Toluidine	ng/mg nicotine	0.962 ± 0.076	43.5 ± 1.45
27. Benzidine	ng/mg nicotine	4/4 < 7E-4	N.D.
*N-Heterocyclic aromatics*
28. Pyridine	µg/mg nicotine	6.343 ± 0.283	18 ± 0.833
29. Quinoline	µg/mg nicotine	0.016 ± 0.001	0.273 ± 0.0276
*Halogen compounds*
30. Vinyl chloride	ng/mg nicotine	4/4 < 2.477	50.2 ± 2.75
*Inorganic compounds*
31. Ammonia	µg/mg nicotine	10.18 ± 0.611	19.4 ± 0.847
32. Hydrogen cyanide	µg/mg nicotine	2.905 ± 0.201	215 ± 17.2
33. Nitric oxide	µg/mg nicotine	11.37 ± 0.521	218 ± 10.3
34. Nitrogen oxides	µg/mg nicotine	11.48 ± 0.516	240 ± 12.3
*Monocyclic aromatics*
35. Benzene	µg/mg nicotine	0.538 ± 0.037	46.8 ± 1.7
36. Styrene	µg/mg nicotine	0.578 ± 0.048	11.9 ± 0.497
37. Toluene	µg/mg nicotine	2.172 ± 0.231	97.8 ± 3.8
*N-nitrosamines*
38. N-Nitrosoanabasine (NAB)	ng/mg nicotine	4/4 < 2.173	18 ± 1.24
39. N-Nitrosoanatabine (NAT)	ng/mg nicotine	11.67 ± 1.224	173 ± 10.1
40. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)	ng/mg nicotine	4.631 ± 0.387	117 ± 5.56
41. N-Nitrosonornicotine (NNN)	ng/mg nicotine	10.37 ± 1.039	155 ± 4.31
*Phenols*
42. Catechol	µg/mg nicotine	15.53 ± 1.698	43.8 ± 2.17
43. m+p-cresol	µg/mg nicotine	0.123 ± 0.02	6.04 ± 0.448
44. o-cresol	µg/mg nicotine	0.102 ± 0.014	2.08 ± 0.18
45. Hydroquinone	µg/mg nicotine	6.614 ± 0.859	40.2 ± 1.85
46. Phenol	µg/mg nicotine	1.617 ± 0.269	6.59 ± 0.497
47. Resorcinol	µg/mg nicotine	0.049 ± 0.004	0.894 ± 0.0364
*PAHs*
48. Benzo[a]pyrene	ng/mg nicotine	3/4 < 0.696	4.66 ± 1.87
49. Benz[a]anthracene	ng/mg nicotine	1.078 ± 0.051	9.21 ± 3.19
50. Dibenz[a,h]anthracene	ng/mg nicotine	4/4 < 0.07	3/8 < 0
51. Pyrene	ng/mg nicotine	4.085 ± 0.24	25.5 ± 15.2
*Metals/Elements*
52. Arsenic	ng/mg nicotine	3/3 < 0.787	3.32 ± 0.209
53. Cadmium	ng/mg nicotine	0.371 ± 0.008	63.7 ± 3.28
54. Chromium	ng/mg nicotine	3/3 < 0.118	4/4 < 0.257
55. Lead	ng/mg nicotine	3/3 < 2.332	14.8 ± 0.773
56. Mercury	ng/mg nicotine	1.024 ± 0.105	1.86 ± 0.0981
57. Nickel	ng/mg nicotine	2/3 < 0.118	4/4 < 0.257
58. Selenium	ng/mg nicotine	3/3 < 0.383	0.687 ± 0.126

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ISO parameters		THS2.2	3R4F
1. Carbon monoxide	mg/mg nicotine	0.437 ± 0.031	14.8 ± 0.715
2. Nicotine	mg/mg nicotine	1 ± 0.045	1 ± 0.0542
3. Tar	mg/mg nicotine	6.304 ± 1.214	14.3 ± 0.717
4. TPM	mg/mg nicotine	34.72 ± 1.396	22.2 ± 1.2
5. Water	mg/mg nicotine	27.41 ± 1.937	7.01 ± 0.673
*Aliphatic dienes*
6. 1,3-Butadiene	µg/mg nicotine	0.298 ± 0.053	36.7 ± 3.6
7. Isoprene	µg/mg nicotine	2.483 ± 0.335	427 ± 36.4
*Carbonyls*
8. Acetaldehyde	µg/mg nicotine	157.9 ± 15.78	719 ± 50.1
9. Acetone	µg/mg nicotine	29.35 ± 3.463	323 ± 11.9
10. Acrolein	µg/mg nicotine	8.165 ± 1.189	77 ± 5.51
11. Butyraldehyde	µg/mg nicotine	20.32 ± 2.024	41.7 ± 3.64
12. Crotonaldehyde	µg/mg nicotine	2.809 ± 0.333	40.5 ± 4.31
13. Formaldehyde	µg/mg nicotine	2.623 ± 0.271	28.3 ± 3.48
14. Methyl ethyl ketone	µg/mg nicotine	5.986 ± 0.91	91.9 ± 5.79
15. Propionaldehyde	µg/mg nicotine	11.75 ± 1.483	58.1 ± 2.68
*Acid derivatives*
16. Acetamide	µg/mg nicotine	3.063 ± 0.283	7.17 ± 0.399
17. Acrylamide	µg/mg nicotine	1.918 ± 0.188	2.03 ± 0.157
18. Acrylonitrile	µg/mg nicotine	0.166 ± 0.013	14.4 ± 0.894
*Epoxides*
19. Ethylene oxide	µg/mg nicotine	0.167 ± 0.011	12.9 ± 0.998
20. Propylene oxide	µg/mg nicotine	0.094 ± 0.008	0.723 ± 0.0234
*Nitro compounds*
21. Nitrobenzene		N.D.	N.D.
*Aromatic Amines*
22. 1-Aminonaphthalene	ng/mg nicotine	0.065 ± 0.007	9.95 ± 0.6
23. 2-Aminonaphthalene	ng/mg nicotine	3/4 < 0.024	5.11 ± 0.186
24. 3-Aminobiphenyl	ng/mg nicotine	0.043 ± 0.005	1.64 ± 0.213
25. 4-Aminobiphenyl	ng/mg nicotine	4/4 < 0.032	1.31 ± 0.115
26. o-Toluidine	ng/mg nicotine	0.962 ± 0.076	43.5 ± 1.45
27. Benzidine	ng/mg nicotine	4/4 < 7E-4	N.D.
*N-Heterocyclic aromatics*
28. Pyridine	µg/mg nicotine	6.343 ± 0.283	18 ± 0.833
29. Quinoline	µg/mg nicotine	0.016 ± 0.001	0.273 ± 0.0276
*Halogen compounds*
30. Vinyl chloride	ng/mg nicotine	4/4 < 2.477	50.2 ± 2.75
*Inorganic compounds*
31. Ammonia	µg/mg nicotine	10.18 ± 0.611	19.4 ± 0.847
32. Hydrogen cyanide	µg/mg nicotine	2.905 ± 0.201	215 ± 17.2
33. Nitric oxide	µg/mg nicotine	11.37 ± 0.521	218 ± 10.3
34. Nitrogen oxides	µg/mg nicotine	11.48 ± 0.516	240 ± 12.3
*Monocyclic aromatics*
35. Benzene	µg/mg nicotine	0.538 ± 0.037	46.8 ± 1.7
36. Styrene	µg/mg nicotine	0.578 ± 0.048	11.9 ± 0.497
37. Toluene	µg/mg nicotine	2.172 ± 0.231	97.8 ± 3.8
*N-nitrosamines*
38. N-Nitrosoanabasine (NAB)	ng/mg nicotine	4/4 < 2.173	18 ± 1.24
39. N-Nitrosoanatabine (NAT)	ng/mg nicotine	11.67 ± 1.224	173 ± 10.1
40. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)	ng/mg nicotine	4.631 ± 0.387	117 ± 5.56
41. N-Nitrosonornicotine (NNN)	ng/mg nicotine	10.37 ± 1.039	155 ± 4.31
*Phenols*
42. Catechol	µg/mg nicotine	15.53 ± 1.698	43.8 ± 2.17
43. m+p-cresol	µg/mg nicotine	0.123 ± 0.02	6.04 ± 0.448
44. o-cresol	µg/mg nicotine	0.102 ± 0.014	2.08 ± 0.18
45. Hydroquinone	µg/mg nicotine	6.614 ± 0.859	40.2 ± 1.85
46. Phenol	µg/mg nicotine	1.617 ± 0.269	6.59 ± 0.497
47. Resorcinol	µg/mg nicotine	0.049 ± 0.004	0.894 ± 0.0364
*PAHs*
48. Benzo[a]pyrene	ng/mg nicotine	3/4 < 0.696	4.66 ± 1.87
49. Benz[a]anthracene	ng/mg nicotine	1.078 ± 0.051	9.21 ± 3.19
50. Dibenz[a,h]anthracene	ng/mg nicotine	4/4 < 0.07	3/8 < 0
51. Pyrene	ng/mg nicotine	4.085 ± 0.24	25.5 ± 15.2
*Metals/Elements*
52. Arsenic	ng/mg nicotine	3/3 < 0.787	3.32 ± 0.209
53. Cadmium	ng/mg nicotine	0.371 ± 0.008	63.7 ± 3.28
54. Chromium	ng/mg nicotine	3/3 < 0.118	4/4 < 0.257
55. Lead	ng/mg nicotine	3/3 < 2.332	14.8 ± 0.773
56. Mercury	ng/mg nicotine	1.024 ± 0.105	1.86 ± 0.0981
57. Nickel	ng/mg nicotine	2/3 < 0.118	4/4 < 0.257
58. Selenium	ng/mg nicotine	3/3 < 0.383	0.687 ± 0.126

ISO parameters		THS2.2	3R4F
1. Carbon monoxide	mg/mg nicotine	0.437 ± 0.031	14.8 ± 0.715
2. Nicotine	mg/mg nicotine	1 ± 0.045	1 ± 0.0542
3. Tar	mg/mg nicotine	6.304 ± 1.214	14.3 ± 0.717
4. TPM	mg/mg nicotine	34.72 ± 1.396	22.2 ± 1.2
5. Water	mg/mg nicotine	27.41 ± 1.937	7.01 ± 0.673
*Aliphatic dienes*
6. 1,3-Butadiene	µg/mg nicotine	0.298 ± 0.053	36.7 ± 3.6
7. Isoprene	µg/mg nicotine	2.483 ± 0.335	427 ± 36.4
*Carbonyls*
8. Acetaldehyde	µg/mg nicotine	157.9 ± 15.78	719 ± 50.1
9. Acetone	µg/mg nicotine	29.35 ± 3.463	323 ± 11.9
10. Acrolein	µg/mg nicotine	8.165 ± 1.189	77 ± 5.51
11. Butyraldehyde	µg/mg nicotine	20.32 ± 2.024	41.7 ± 3.64
12. Crotonaldehyde	µg/mg nicotine	2.809 ± 0.333	40.5 ± 4.31
13. Formaldehyde	µg/mg nicotine	2.623 ± 0.271	28.3 ± 3.48
14. Methyl ethyl ketone	µg/mg nicotine	5.986 ± 0.91	91.9 ± 5.79
15. Propionaldehyde	µg/mg nicotine	11.75 ± 1.483	58.1 ± 2.68
*Acid derivatives*
16. Acetamide	µg/mg nicotine	3.063 ± 0.283	7.17 ± 0.399
17. Acrylamide	µg/mg nicotine	1.918 ± 0.188	2.03 ± 0.157
18. Acrylonitrile	µg/mg nicotine	0.166 ± 0.013	14.4 ± 0.894
*Epoxides*
19. Ethylene oxide	µg/mg nicotine	0.167 ± 0.011	12.9 ± 0.998
20. Propylene oxide	µg/mg nicotine	0.094 ± 0.008	0.723 ± 0.0234
*Nitro compounds*
21. Nitrobenzene		N.D.	N.D.
*Aromatic Amines*
22. 1-Aminonaphthalene	ng/mg nicotine	0.065 ± 0.007	9.95 ± 0.6
23. 2-Aminonaphthalene	ng/mg nicotine	3/4 < 0.024	5.11 ± 0.186
24. 3-Aminobiphenyl	ng/mg nicotine	0.043 ± 0.005	1.64 ± 0.213
25. 4-Aminobiphenyl	ng/mg nicotine	4/4 < 0.032	1.31 ± 0.115
26. o-Toluidine	ng/mg nicotine	0.962 ± 0.076	43.5 ± 1.45
27. Benzidine	ng/mg nicotine	4/4 < 7E-4	N.D.
*N-Heterocyclic aromatics*
28. Pyridine	µg/mg nicotine	6.343 ± 0.283	18 ± 0.833
29. Quinoline	µg/mg nicotine	0.016 ± 0.001	0.273 ± 0.0276
*Halogen compounds*
30. Vinyl chloride	ng/mg nicotine	4/4 < 2.477	50.2 ± 2.75
*Inorganic compounds*
31. Ammonia	µg/mg nicotine	10.18 ± 0.611	19.4 ± 0.847
32. Hydrogen cyanide	µg/mg nicotine	2.905 ± 0.201	215 ± 17.2
33. Nitric oxide	µg/mg nicotine	11.37 ± 0.521	218 ± 10.3
34. Nitrogen oxides	µg/mg nicotine	11.48 ± 0.516	240 ± 12.3
*Monocyclic aromatics*
35. Benzene	µg/mg nicotine	0.538 ± 0.037	46.8 ± 1.7
36. Styrene	µg/mg nicotine	0.578 ± 0.048	11.9 ± 0.497
37. Toluene	µg/mg nicotine	2.172 ± 0.231	97.8 ± 3.8
*N-nitrosamines*
38. N-Nitrosoanabasine (NAB)	ng/mg nicotine	4/4 < 2.173	18 ± 1.24
39. N-Nitrosoanatabine (NAT)	ng/mg nicotine	11.67 ± 1.224	173 ± 10.1
40. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)	ng/mg nicotine	4.631 ± 0.387	117 ± 5.56
41. N-Nitrosonornicotine (NNN)	ng/mg nicotine	10.37 ± 1.039	155 ± 4.31
*Phenols*
42. Catechol	µg/mg nicotine	15.53 ± 1.698	43.8 ± 2.17
43. m+p-cresol	µg/mg nicotine	0.123 ± 0.02	6.04 ± 0.448
44. o-cresol	µg/mg nicotine	0.102 ± 0.014	2.08 ± 0.18
45. Hydroquinone	µg/mg nicotine	6.614 ± 0.859	40.2 ± 1.85
46. Phenol	µg/mg nicotine	1.617 ± 0.269	6.59 ± 0.497
47. Resorcinol	µg/mg nicotine	0.049 ± 0.004	0.894 ± 0.0364
*PAHs*
48. Benzo[a]pyrene	ng/mg nicotine	3/4 < 0.696	4.66 ± 1.87
49. Benz[a]anthracene	ng/mg nicotine	1.078 ± 0.051	9.21 ± 3.19
50. Dibenz[a,h]anthracene	ng/mg nicotine	4/4 < 0.07	3/8 < 0
51. Pyrene	ng/mg nicotine	4.085 ± 0.24	25.5 ± 15.2
*Metals/Elements*
52. Arsenic	ng/mg nicotine	3/3 < 0.787	3.32 ± 0.209
53. Cadmium	ng/mg nicotine	0.371 ± 0.008	63.7 ± 3.28
54. Chromium	ng/mg nicotine	3/3 < 0.118	4/4 < 0.257
55. Lead	ng/mg nicotine	3/3 < 2.332	14.8 ± 0.773
56. Mercury	ng/mg nicotine	1.024 ± 0.105	1.86 ± 0.0981
57. Nickel	ng/mg nicotine	2/3 < 0.118	4/4 < 0.257
58. Selenium	ng/mg nicotine	3/3 < 0.383	0.687 ± 0.126

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B. Total weights per chemical classes, manufacturer’s specifications.

Chemical class	Unit weight per stick	Total weight		% reduction
Chemical class	Unit weight per stick	3R4F	THS2.2	% reduction
Carbon monoxide	mg	32.8	0.531	98.4%
Carbonyls	µg	2970.7	328.45	88.9%
Nitrogen oxides	µg	1028	34.1	96.7%
Aliphatic dienes	µg	861.8	2.644	99.7%
Inorganic compounds	µg	532.3	19.01	96.4%
Monocyclic aromatic HC	µg	310.1	3.847	98.8%
Phenols	µg	206.62	25.771	87.5%
Acid derivatives	µg	50.63	6.008	88.1%
N-Heterocyclic aromatics	µg	36.613	7.552	79.4%
Epoxides	µg	30.72	0.349	98.9%
TSNA	ng	926.7	47.52*	94.9%
Elements	ng	214.03	7.65*	96.4%
PAHs	ng	131.2	7.55*	94.2%
Aromatic amines	ng	124.33	1.466*	98.8%
Halogen compounds	ng	96.7	3.54*	96.3%
Nitro compounds	ng	0.499	0.09	82.0%

Chemical class	Unit weight per stick	Total weight		% reduction
Chemical class	Unit weight per stick	3R4F	THS2.2	% reduction
Carbon monoxide	mg	32.8	0.531	98.4%
Carbonyls	µg	2970.7	328.45	88.9%
Nitrogen oxides	µg	1028	34.1	96.7%
Aliphatic dienes	µg	861.8	2.644	99.7%
Inorganic compounds	µg	532.3	19.01	96.4%
Monocyclic aromatic HC	µg	310.1	3.847	98.8%
Phenols	µg	206.62	25.771	87.5%
Acid derivatives	µg	50.63	6.008	88.1%
N-Heterocyclic aromatics	µg	36.613	7.552	79.4%
Epoxides	µg	30.72	0.349	98.9%
TSNA	ng	926.7	47.52*	94.9%
Elements	ng	214.03	7.65*	96.4%
PAHs	ng	131.2	7.55*	94.2%
Aromatic amines	ng	124.33	1.466*	98.8%
Halogen compounds	ng	96.7	3.54*	96.3%
Nitro compounds	ng	0.499	0.09	82.0%

*Measurement replaced by lower limit of quantification.

Remarks: Smoke/aerosol generation according to Health Canada regimen (Burnset al., 2008). These numbers are provided to illustrate the reduction in HPHCs per chemical class and were derived from later product batches.

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B. Total weights per chemical classes, manufacturer’s specifications.

Chemical class	Unit weight per stick	Total weight		% reduction
Chemical class	Unit weight per stick	3R4F	THS2.2	% reduction
Carbon monoxide	mg	32.8	0.531	98.4%
Carbonyls	µg	2970.7	328.45	88.9%
Nitrogen oxides	µg	1028	34.1	96.7%
Aliphatic dienes	µg	861.8	2.644	99.7%
Inorganic compounds	µg	532.3	19.01	96.4%
Monocyclic aromatic HC	µg	310.1	3.847	98.8%
Phenols	µg	206.62	25.771	87.5%
Acid derivatives	µg	50.63	6.008	88.1%
N-Heterocyclic aromatics	µg	36.613	7.552	79.4%
Epoxides	µg	30.72	0.349	98.9%
TSNA	ng	926.7	47.52*	94.9%
Elements	ng	214.03	7.65*	96.4%
PAHs	ng	131.2	7.55*	94.2%
Aromatic amines	ng	124.33	1.466*	98.8%
Halogen compounds	ng	96.7	3.54*	96.3%
Nitro compounds	ng	0.499	0.09	82.0%

Chemical class	Unit weight per stick	Total weight		% reduction
Chemical class	Unit weight per stick	3R4F	THS2.2	% reduction
Carbon monoxide	mg	32.8	0.531	98.4%
Carbonyls	µg	2970.7	328.45	88.9%
Nitrogen oxides	µg	1028	34.1	96.7%
Aliphatic dienes	µg	861.8	2.644	99.7%
Inorganic compounds	µg	532.3	19.01	96.4%
Monocyclic aromatic HC	µg	310.1	3.847	98.8%
Phenols	µg	206.62	25.771	87.5%
Acid derivatives	µg	50.63	6.008	88.1%
N-Heterocyclic aromatics	µg	36.613	7.552	79.4%
Epoxides	µg	30.72	0.349	98.9%
TSNA	ng	926.7	47.52*	94.9%
Elements	ng	214.03	7.65*	96.4%
PAHs	ng	131.2	7.55*	94.2%
Aromatic amines	ng	124.33	1.466*	98.8%
Halogen compounds	ng	96.7	3.54*	96.3%
Nitro compounds	ng	0.499	0.09	82.0%

*Measurement replaced by lower limit of quantification.

Published by Oxford University Press on behalf of the Society of Toxicology 2016.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]

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An 8-Month Systems Toxicology Inhalation/Cessation Study in Apoe^−/− Mice to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared With Conventional Cigarettes

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An 8-Month Systems Toxicology Inhalation/Cessation Study in Apoe^−/− Mice to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared With Conventional Cigarettes