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. Author manuscript; available in PMC: 2022 Oct 28.
Published in final edited form as: Food Chem Toxicol. 2022 May 25;165:113179. doi: 10.1016/j.fct.2022.113179

Table:

A total of 83 tobacco and tobacco smoke components have been classified as carcinogens by IARC as of 2022. Group 1 carcinogens: 18; group 2A carcinogens: 15; group 2B carcinogens: 50.

Class Name and CAS number IARC
Group		 Degree of evidence of
carcinogenicitya 		Most
recent
volume		 Year Hecht
listb 		U.S. FDA
listc 		Occurrence in tobacco mainstream smoked,e,f Occurrence in unburned tobacco
Human Animal
Hydrocarbons (22 compounds)
Alkenes (3) 1,3-Butadiene (106-99-0) 1 Suffic. Suffic. 100F 2012 × × 6.4 – 68.7 μg/cig (Hecht, 2012)
12.2 – 27.6 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
20.2 – 35.1 (ISO) or 80.9 – 90.5 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
7.6 – 60.4 (ISO) or 67.8 – 118.3 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
50 ± 21 (ISO) or 150 ± 30 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
94 ± 14 (ISO) or 180 ± 20 (CI) μg/little cigar (mean ± SD) in 60 U.S. brands (Vu et al., 2021)
Isoprene (78-79-5) 2B ND Suffic. 71 1999 × × 70 – 586 μg/cig (Hecht, 2012) <8 – 22.5 ng/g in unheated waterpipe tobacco solid waste (Hsieh et al., 2021)
1.1 – 2.9 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
207 – 373 (ISO) or 870 – 1013 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
93 ± 39 (ISO) or 290 ± 60 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
379 ± 57 (ISO) or 644 ± 94 (CI) μg/little cigar (mean ± SD) in 60 U.S. brands (Vu et al., 2021)
Styrene (100-42-5) 2A Limited Suffic. 121 2019 × × nd – 48 μg/cig (Hecht, 2012)
12.2 – 27.6 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
2.7 – 6.0 (ISO) or 15.0 – 20.0 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
0.18 – 5.36 (ISO) or 10.5 – 22.0 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
7.2 ± 1.2 μg/puff (mean ± SD) in bidi smoke (Oladipupo et al., 2019)
11 ± 6 (ISO) or 45 ± 8 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
Monocyclic Aromatic Hydrocarbons (MAH, 3) Benzene (71-43-2) 1 Suffic. Suffic. 120 2018 × × 6.1 – 58.9 μg/cig (Hecht, 2012)
45.7 – 119.5 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
27.9 – 45.5 (ISO) or 83.5 – 98.5 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
6.2 – 48.7 (ISO) or 58.7 – 128.5 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
46 ± 19 (ISO) or 130 ± 20 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
111 ± 13 (ISO) or 216 ± 18 (CI) μg/little cigar (mean ± SD) in 60 U.S. brands (Vu et al., 2021)
Ethylbenzene (100-41-4) 2B Inade. Suffic. 77 2000 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
0.41 – 6.13 (ISO) or 9.7 – 21.6 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
12 ± 6 (ISO) or 40 ± 6 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
Cumene (98-82-8) 2B ND Suffic. 101 2012 7 – 14 μg/cig (International Agency for Research on Cancer, 2012d)
Polycyclic Aromatic Hydrocarbons (PAH, 16) Naphthalene (NAP, 91-20-3) 2B Inade. Suffic. 82 2002 × × 65 – 868 ng/cig (Hecht, 2012) ~360 ng/g in Alaskan lq’mik smokeless tobacco and 360 ng/g in Copenhagen snuff (Hearn et al., 2013)
0.8 – 3.3 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012) Present (Oldham et al., 2014)
Present (Oldham et al., 2014) nd – 351.2 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
0.1 – 324.0 ng/cig in 13 Chinese brands (Gao et al., 2015)
14 – 804 (ISO) or 608 – 2120 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015)
0.02 ± 0.10 (ISO) or 0.8 ± 0.6 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
Benz[a]anthracene (B[a]A, 56-55-3) 2B ND Suffic. 92 2010 × × 2.6 – 26.8 ng/cig (Hecht, 2012) 36 – 292 ng/g in Alaskan lq’mik smokeless tobacco and 81 ng/g in Copenhagen snuff (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
2.0 – 56.4 ng/cig in 13 Chinese brands (Gao et al., 2015) nd – 769.0 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
3.7 – 39 (ISO) or 21 – 59 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015)
15 – 74 (ISO) or 35 – 100 (CI) ng/cig in 13 Natural American Spirit cigarettes and 17 – 34 (ISO) or 33 – 53 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Benzo[c]phenanthrene (B[c]P, 195-19-7) 2B ND Limited 92 2010 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
nd – 18.6 ng/cig in 13 Chinese brands (Gao et al., 2015)
Chrysene (CHR, 218-01-9) 2B ND Suffic. 92 2010 × × 2.6 – 24.7 ng/cig (Hecht, 2012) 37 – 359 ng/g in Alaskan lq’mik smokeless tobacco) and 97 ng/g in Copenhagen snuff (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
2.5 – 64.4 ng/cig in 13 Chinese brands (Gao et al., 2015) <1.42 – 211 ng/g wet weight in Rapé tobacco products (Stanfill et al., 2015)
4.5 – 61 (ISO) or 30 – 97 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015) nd – 936.7 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
23 – 103 (ISO) or 52 – 145 (CI) ng/cig in 13 Natural American Spirit cigarettes and 24 – 43 (ISO) or 51 – 69 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
5-Methylchrysene (3697-24-3) 2B ND Suffic. 92 2010 × × nd – 2 ng/cig (Hecht, 2012) nd – 18 ng/g in Alaskan lq’mik smokeless tobacco and 8.4 ng/g in Copenhagen snuff (Hearn et al., 2013)
Present (Oldham et al., 2014)
<1.5 ng/cig in 3R4F cigarette (Jeffery et al., 2018)
Benz[j]aceanthrylene (B[j]A, 202-33-5) 2B ND Limited 92 2010 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
<2.5 ng/cig in 3R4F cigarette (Jeffery et al., 2018)
Benzo[b]fluoranthene (B[b]F, 205-99-2) 2B ND Suffic. 92 2010 × × 1.3 – 17.0 ng/cig (Hecht, 2012) 19.4 – 68 ng/g in Alaskan lq’mik smokeless tobacco and 31 ng/g in Copenhagen snuff ng/g (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
0.5 – 17.7 ng/cig in 13 Chinese brands (Gao et al., 2015) <0.79 – 23.2 ng/g wet weight in Rapé tobacco products (Stanfill et al., 2015)
1.9 – 22 (ISO) or 15 – 37 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015) nd – 203.9 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
Benzo[j]fluoranthene (B[j]F, 205-82-3) 2B ND Suffic. 92 2010 × 1.8 – 24 ng/cig (Hecht, 2012) 18 – 63 ng/g in Alaskan lq’mik smokeless tobacco and 30 ng/g in Copenhagen snuff (Hearn et al., 2013)
B[b]F plus B[j]F: 10 – 41 (ISO) or 26 – 50 (CI) ng/cig in 13 Natural American Spirit cigarettes and 12 – 22 (ISO) or 27 – 37 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019) nd – 1052.8 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
Benzo[k]fluoranthene (B[k]F, 207-08-9) 2B ND Suffic. 92 2010 × × 0.5 – 3.3 ng/cig (Hecht, 2012) 5.4 – 39 (Alaskan lq’mik smokeless tobacco) and 10 (Copenhagen snuff) ng/g (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
0.6 – 17.1 ng/cig in 13 Chinese brands (Gao et al., 2015) <0.53 – 9.83 ng/g wet weight in Rapé tobacco products (Stanfill et al., 2015)
0.7 – 3.7 (ISO) or 2.0 – 7.0 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015) nd – 921.4 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
1.4 – 7.7 (ISO) or 2.0 – 3.8 (CI) ng/cig in 13 Natural American Spirit cigarettes and 12 – 22 (ISO) or 4.1 – 6.5 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Cyclopenta[cd]pyrene (CP[cd]P, 27208-37-3) 2A ND Suffic. 92 2010 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
0.5 – 12.1 ng/cig in 13 Chinese brands (Gao et al., 2015)
Indeno[1,2,3-cd]pyrene (I[cd]P, 193-39-5) 2B ND Suffic. 92 2010 × × 0.65 – 11.2 ng/cig (Hecht, 2012) 30 – 77 ng/g in Alaskan lq’mik smokeless tobacco and 36 ng/g in Copenhagen snuff (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
0.3 – 18.1 ng/cig in 13 Chinese brands (Gao et al., 2015) nd – 446.8 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
2.6 – 17.3 (ISO) or 7.4 – 23 (CI) ng/cig in 13 Natural American Spirit cigarettes and 8.8 – 15.9 (ISO) or 8.4 – 13 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Dibenz[a,h]anthracene (DB[ah]A, 53-70-3) 2A ND Suffic. 92 2010 × × nd – 6 ng/cig (Hecht, 2012) 5.7 – 19 (Alaskan lq’mik smokeless tobacco) and 6.3 (Copenhagen snuff) ng/g (Hearn et al., 2013)
Present (Oldham et al., 2014) Detectable (Oldham et al., 2014)
0.1 – 3.3 ng/cig in 13 Chinese brands (Gao et al., 2015) nd – 97.3 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
3.8 – 8.6 (ISO) or 6.1 – 10 (CI) ng/cig in 13 Natural American Spirit cigarettes and 3.0 – 4.8 (ISO) or 5.0 – 6.9 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Benzo[a]pyrene (B[a]P, 50-32-8) 1 ND Suffic. 100F 2012 × × 1.0 – 15.2 ng/cig (Hecht, 2012) 13 – 104 (Alaskan lq’mik smokeless tobacco) and 27 (Copenhagen snuff) ng/g (Hearn et al., 2013)
Present (Oldham et al., 2014) Present (Oldham et al., 2014)
1.1 – 41.6 ng/cig in 13 Chinese brands (Gao et al., 2015) 3.51 – 24.3 ng/g wet weight in Rapé tobacco products (Stanfill et al., 2015)
2.1 – 22 (ISO) or 13 – 38 (CI) ng/cig in 35 top-selling U.S. brands (Vu et al., 2015) <0.5 – 1.9 ng/g unheated waterpipe tobacco solid waste (Hsieh et al., 2021)
4.43 – 8.03 (ISO) or 13.04 – 17.27 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) nd – 366.8 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
4 – 44 ng/cig in 43 Chinese brands (Yershova et al., 2016)
2.0 – 8.7 (ISO) or 6.3 – 17.8 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
8.0 – 34.8 (ISO) or 15 – 38 (CI) ng/cig in 13 Natural American Spirit cigarettes and 8.8 – 15.9 (ISO) or 18 – 23 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Dibenzo[a,h]pyrene (DB[ah]P, 189-64-0) 2B ND Suffic. 92 2010 × × 5 – 9.5 ng/cig (Hecht, 2012)
Detectable (Oldham et al., 2014)
0.1 – 1.1 ng/cig in 3R4F cigarette (Jeffery et al., 2018)
Dibenzo[a,i]pyrene (DB[ai]P, 189-55-9) 2B ND Suffic. 92 2010 × × 0.7 – 1.2 ng/cig (Hecht, 2012) 1.4 – 2.2 ng/g in Alaskan lq’mik smokeless tobacco) and 1.5 ng/g in Copenhagen snuff (Hearn et al., 2013)
Present (Oldham et al., 2014)
0.1 – 0.8 ng/cig in 3R4F cigarette (Jeffery et al., 2018)
Dibenzo[a,l]pyrene (DB[al]P, 191-30-0) 2A ND Suffic. 92 2010 × × 0.1 ng (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
0.03 or 0.1 ng/cig in 3R4F cigarette (Jeffery et al., 2018)
Amines (22 compounds)
Aliphatic Amine (1) Hydrazine (302-01-2) 2A Limited Suffic. 115 2018 × × 24 – 57 ng/cig (Hecht, 2012)
Detectable (Oldham et al., 2014)
Aromatic Amines (AA, 6) Aniline (62-53-3) 2A Inade. Suffic. 127 2021 430 – 9570 or 120 – 809 or 129 – 838 ng/cig (International Agency for Research on Cancer, 2021b)
ortho-Toluidine (95-53-4) 1 Suffic. Suffic. 100F 2012 × × 8.6 – 144 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
21.2 – 99.9 (ISO) or 115.7 – 206.9 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
6.89 – 46.75 (ISO) or 53.18 – 149.70 (CI) ng/cig in 16 top-selling Chinese cigarettes (Zhang et al., 2017)
2,6-Dimethylaniline (87-62-7) 2B ND Suffic. 57 1993 × × 3.6 – 18 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
7.1 – 37.4 (ISO) or 34.4 – 74.7 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
0.38 – 1.63 (ISO) or 0.64 – 2.67 (CI) ng/cig in 16 top-selling Chinese cigarettes (Zhang et al., 2017)
ortho-Anisidine (90-04-0) 2A Inade. Suffic. 127 2021 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
0.7 – 2.6 (ISO) or 1.7 – 5.7 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
0.23 – 1.52 (ISO) or 1.02 – 3.98 (CI) ng/cig in 16 top-selling Chinese cigarettes (Zhang et al., 2017)
4-Aminobiphenyl (4-ABP, 92-67-1) 1 Suffic. Suffic. 100F 2012 × × 0.3 – 3.3 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
0.83 – 1.61 (ISO) or 2.60 – 3.64 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015)
1.2 – 4.6 (ISO) or 5.6 – 11.1 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
0.16 – 1.36 (ISO) or 0.38 – 5.95 (CI) ng/cig in 16 top-selling Chinese cigarettes (Zhang et al., 2017)
2-Naphthylamine (2-NA, 91-59-8) 1 Suffic. Suffic. 100F 2012 × × 1.47 – 17.2 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
4.7 – 9.9 (ISO) or 10.9 – 16.6 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015)
3.6 – 15.1 (ISO) or 17.1 – 36.3 (CI) ng/cig in SPECTRUM research cigarettes (Ding et al., 2017)
0.35 – 1.88 (ISO) or 0.89 – 4.60 (CI) ng/cig in 16 top-selling Chinese cigarettes (Zhang et al., 2017)
Heterocyclic Aromatic Amines (HAA, 15) 2-Methylimidazole (693-98-1) 2B ND Suffic. 101 2012 Possibly present (International Agency for Research on Cancer, 2012a)
4-Methylimidazole (822-36-6) 2B ND Suffic. 101 2012 2.3 – 15 μg/cig (International Agency for Research on Cancer, 2012b)
Pyridine (110-86-1) 2B Inade. Suffic. 119 2019 31.1 ± 1.7 (ISO) or 59 ± 4.9 (CI) μg/cig (mean ± SD) in a Canadian cigarette brand (Moir et al., 2008)
2.00 – 13.10 μg/cig in 10 Indian popular cigarettes (Saha et al., 2010)
3 – 28 μg/cig (International Agency for Research on Cancer, 2019a)
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 105650-23-5) 2B Inade. Suffic. 56 1993 × × 11 – 23 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
Quinoline (91-22-5) 2B Inade. Suffic. 121 2019 1.31 ± 0.08 (ISO) μg/cig (mean ± SD) in a Canadian cigarette brand (Moir et al., 2008)
0.07 – 1.19 μg/cig in 10 Indian popular cigarettes (Saha et al., 2010)
0.23 – 0.30 μg/cig (International Agency for Research on Cancer, 2019b)
2-Amino-9H-pyrido[2,3-b]indole (A-α-C, 26148-68-5) 2B ND Suffic. Sup 7 1987 × × nd – 260 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
49 – 160 ng/cig in U.S. commercial cigarettes (Zhang et al., 2011)
2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA-α-C, 68006-83-7) 2B ND Suffic. Sup 7 1987 × × 2 – 37 ng/cig (Hecht, 2012)
Present (Oldham et al., 2014)
3.1 – 9.7 ng/cig in U.S. commercial cigarettes (Zhang et al., 2011)
3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1, 62450-06-0) 2B ND Suffic. Sup 7 1987 × × 0.2 – 0.3 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
0.6 – 2.4 ng/cig in U.S. commercial cigarettes (Zhang et al., 2011)
3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2, 62450-07-1) 2B ND Suffic. Sup 7 1987 × × nd – 0.2 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
1.8 – 9.2 ng/cig in U.S. commercial cigarettes (Zhang et al., 2011)
2-Aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2, 67730-10-3) 2B ND Suffic. Sup 7 1987 × × 0.25 – 0.88 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1, 67730-11-4) 2B ND Suffic. Sup 7 1987 × × nd – 0.89 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ, 76180-96-6) 2A Inade. Suffic. 56 1993 × × 0.3 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
7H-Dibenzo[c,g]carbazole (194-59-2) 2B ND Suffic. 103 2013 × nd – 0.7 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
Dibenz[a,h]acridine (226-36-8) 2B ND Suffic. 103 2013 × nd – 0.1 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
Dibenz[a,j]acridine (224-42-0) 2A ND Suffic. 103 2013 × nd – 10 ng/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
N-Nitrosamines (11 compounds)
Acylic N-Nitrosamines (7) N-Nitrosodimethylamine (NDMA) (62-75-9) 2A ND Suffic. Sup 7 1987 × × nd – 7.9 ng/cig (Hecht, 2012) <LOQ – 39.8 and <LOQ – 24.5 ng/g dry weight in U.S. and Swedish smokeless tobacco, respectively. (Borgerding et al., 2012)
Present (Oldham et al., 2014) Detectable (Oldham et al., 2014)
<LOQ – 8.7 ng/g in 7 different Chinese tobacco samples (Lv et al., 2016)
nd – 8.9 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
N-Nitrosoethylmethylamine (NEMA, 10595-95-6) 2B ND Suffic. Sup 7 1987 × × nd – 0.2 ng/cig (Hecht, 2012)
Detectable (Oldham et al., 2014)
N-Nitrosodiethylamine (NDEA, 55-18-5) 2A ND Suffic. Sup 7 1987 × × nd – 7.6 ng/cig (Hecht, 2012) 0.5 ng/g in one out of 7 different Chinese tobacco samples (Lv et al., 2016)
Detectable (Oldham et al., 2014)
N-Nitrosodi-n-butylamine (NDBA, 924-16-3) 2B ND Suffic. Sup 7 1987 nd – 1.4 ng/g in 7 different Chinese tobacco samples (Lv et al., 2016)
N-Nitrososarcosine (NSAR, 13256-22-9) 2B ND Suffic. Sup 7 1987 × 22 – 460 ng/cig (National Toxicology Program, 2016) 550.5 ± 43.7 ng/g in one U.S. dry snuff (Wu et al., 2012b)
29.9 and 61.9 ng/g in 2 U.S. smokeless tobacco products (Werneth et al., 2021)
N-Nitrosodiethanolamine (NDELA, 1116-54-7) 2B Inade. Suffic. 77 2000 × × nd – 290 ng/cig (Hecht, 2012) Detectable (Oldham et al., 2014)
Present (Oldham et al., 2014)
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 64091-91-4) 1 Inade. Suffic. 100E 2012 × × 25.6 – 146.1 ng/cig in 17 U.S. cigarette brands (Stepanov et al., 2012) <LOQ – 6761 and <LOQ – 319 ng/g dry weight in U.S. and Swedish smokeless tobacco, respectively (Borgerding et al., 2012)
21.4 – 50.5 (ISO) or 78.1 – 151.3 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.34 – 0.91 μg/g wet weight in the tobacco filler of 17 U.S. cigarette brands (Stepanov et al., 2012)
3.3 – 63.9 ng/cig in 43 Chinese cigarette brands (Yershova et al., 2016) 0.109 – 4.57 μg/g dry weight in selected Indian smokeless tobacco products (Stepanov et al., 2017b)
13 – 122.4 (ISO) or 39.9 – 245.9 (CI) ng/cig in 50 U.S. cigarette brands (Edwards et al., 2017) 0.185 – 1.13 μg/g in 216 U.S. snus and dissolvable tobacco products (Stepanov et al., 2014a)
9.2 – 39 (ISO) or 38 – 128 (CI) ng/cig in 13 Natural American Spirit cigarettes and 71 – 121 (ISO) or 129 – 198 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019) 0.19 – 3.44 μg/g wet weight in 31 U.S. smokeless tobacco brands (Hatsukami et al., 2015)
89 – 879 (ISO) or 138 – 1570 (CI) ng/cigar in 60 U.S. little cigars (Edwards et al., 2021) 1.2 – 5.0 μg/g wet weight in Chaini Khaini from Indian market (Stepanov et al., 2015)
0.032 – 1.35 μg/g in the tobacco filler of 43 Chinese cigarette brands (Yershova et al., 2016)
192 ± 21 (prepackaged) and 71 ± 4 (bulk) ng/g wet weight (mean ± SD) in nasvai from Kyrgyzstan (Stepanov et al., 2017a)
193.9 – 1092.9 ng/g in cigarette filler of 50 U.S. brands (Edwards et al., 2017)
0.11 – 0.35 μg/g in cigarette filler of 13 Natural American Spirit cigarette varieties and 0.11 – 0.35 μg/g in cigarette filler of 5 U.S. popular cigarette brands (Jain et al., 2019)
0.72 – 34 and 3.7 – 9.7 μg/g wet weight in two Bangladeshi smokeless tobacco products Zarda and Gul, respectively (Nasrin et al., 2020)
321 ± 68.1 ng/g wet weight (mean ± SD) in 8 U.S. snus products (Lawler et al., 2020)
26 – 2950 ng/g in the tobacco filler of 60 U.S. little cigars (Edwards et al., 2021)
Cyclic N-Nitrosamines (4) N-Nitrosopyrrolidine (NPYR, 930-55-2) 2B ND Suffic. Sup 7 1987 × × nd – 19.7 ng/cig (Hecht, 2012) Present (Oldham et al., 2014)
Present (Oldham et al., 2014) nd – 30.7 ng/g in 7 different Chinese tobacco samples (Lv et al., 2016)
1.1 – 13.5 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
N′-Nitrosonornicotine (NNN, 16543-55-8) 1 Inade. Suffic. 100E 2012 × × 19.5 – 232.1 ng/cig in 17 U.S. cigarette brands (Stepanov et al., 2012) <LOQ – 14424 and <LOQ – 1318 ng/g dry weight in U.S. and Swedish smokeless tobacco products, respectively (Borgerding et al., 2012)
60.4 – 138.7 (ISO) or 163.5 – 329.1 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.33 – 4.03 μg/g wet weight in tobacco filler of 17 U.S. cigarette brands (Stepanov et al., 2012)
1.8 – 135.3 ng/cig in 43 Chinese cigarette brands (Yershova et al., 2016) 0.457 – 37.0 μg/g dry weight in selected Indian smokeless tobacco products (Stepanov et al., 2017b)
17.2 – 171.1 (ISO) or 32.8 – 323.3 (CI) ng/cig in 50 U.S. cigarette brands (Edwards et al., 2017) 0.267 – 2.66 μg/g in 216 U.S. snus and dissolvable tobacco products (Stepanov et al., 2014a)
7.1 – 113 (ISO) or 32 – 323 (CI) ng/cig in 13 Natural American Spirit cigarettes and 117 – 165 (ISO) or 237 – 382 (CI) ng/cig in 5 U.S. popular cigarette brands (Jain et al., 2019) 0.48 – 11.11 μg/g wet weight in 31 U.S. smokeless tobacco brands (Hatsukami et al., 2015)
201 – 1450 (ISO) or 445 – 2780 (CI) ng/cigar ng/cigar in 60 U.S. little cigars (Edwards et al., 2021) 13.2 – 29.4 μg/g wet weight in Chaini Khaini from Indian market (Stepanov et al., 2015)
0.020 – 4.67 μg/g in tobacco filler of 43 Chinese cigarette brands (Yershova et al., 2016)
1189 ± 68 (prepackaged) and 642 ± 53 (bulk) ng/g wet weight (mean ± SD) in nasvai from Kyrgyzstan (Stepanov et al., 2017a)
0.14 – 1.76 μg/g in cigarette filler of 13 Natural American Spirit cigarette varieties and 0.99 – 2.06 μg/g in cigarette filler of 5 U.S. popular cigarette brands (Jain et al., 2019)
305.7 – 2970 ng/g in the tobacco filler of 50 U.S. cigarette brands (Edwards et al., 2017)
2.8 – 59 and 13 – 25 μg/g wet weight in two Bangladeshi smokeless tobacco products Zarda and Gul, respectively (Nasrin et al., 2020)
1050 ± 168 ng/g wet weight (mean ± SD) in 8 U.S. snus products (Lawler et al., 2020)
1440 – 12100 ng/g in the tobacco filler of 60 U.S. little cigars (Edwards et al., 2021)
N-Nitrosopiperidine (NPIP, 100-75-4) 2B ND Suffic. Sup 7 1987 × × nd – 231 ng/cig (Hecht, 2012) Barely detectable (Oldham et al., 2014)
Barely detectable (Oldham et al., 2014) nd – 9.1 ng/g in 7 different Chinese tobacco samples (Lv et al., 2016)
nd – 5.2 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
N-Nitrosomorpholine (NMOR, 59-89-2) 2B ND Suffic. Sup 7 1987 × Detectable (Oldham et al., 2014)
nd – 2.7 ng/g in 7 different Chinese tobacco samples (Lv et al., 2016)
nd – 4.4 ng/g in 18 Chinese smokeless tobacco products (Wang et al., 2021)
Ethers (4 compounds)
Ethylene oxide (75-21-8) 1 Limited Suffic. 100F 2012 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
Methyleugenol (93-15-2) 2B ND Suffic. 101 2012 0.018 – 0.021 μg/g in U.S. cigarettes and 0.49 – 61 μg/g in U.S. and Indian bidi cigarettes (International Agency for Research on Cancer, 2012c)
Furan (110-00-9) 2B Inade. Suffic. 63 1995 × × 18 – 65 μg/cig (Hecht, 2012)
7.2 – 16.1 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
4.7 – 34.1 (ISO) or 32.4 – 68.3 μg/cig (CI) in 50 U.S. brands (Pazo et al., 2016)
Benzofuran (271-89-6) 2B Inade. Suffic. 63 1995 × × Present (Hecht, 2012)
Present (Oldham et al., 2014)
Aldehydes (4 compounds)
Formaldehyde (50-00-0) 1 Suffic. Suffic. 100F 2012 × × 1.6 – 75.5 μg/cig (Hecht, 2012) Present (Oldham et al., 2014)
Present (Oldham et al., 2014) 0.2 – 5.4 μg/g in unheated waterpipe tobacco solid waste (Hsieh et al., 2021)
9.0 – 34.3 (ISO) or 46.8 – 92.7 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
55 – 108 (CI) μg/cig in U.S. commercial cigarettes (Ding et al., 2016)
ND – 24.5 (ISO) or 3.4 – 45.6 (CI) μg/cig in SPECTRUM research cigarettes (Ding et al., 2017)
20 ± 13 (ISO) or 67 ± 20 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
9.0 – 75 (ISO) or 61 – 267 (CI) μg/cig in 13 Natural American Spirit cigarettes and 22 – 62 (ISO) or 65 – 149 (CI) μg/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
Acetaldehyde (75-07-0) 2B Inade. Suffic. 71 1999 × × 32 – 828 μg/cig (Hecht, 2012) Present (Oldham et al., 2014)
249.5 – 528.3 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012)
Present (Oldham et al., 2014)
243 – 428 (ISO) or 973 – 1103 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
1198 – 1947 (CI) μg/cig in U.S. commercial cigarettes (Ding et al., 2016)
126 – 1143 (ISO) or 1098 – 2244 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
434 – 1129 (ISO) or 1658 – 2170 (CI) μg/cig in SPECTRUM research cigarettes (Ding et al., 2017)
477 – 921 (ISO) or 1245 – 1523 (CI) μg/cig in 13 Natural American Spirit cigarettes and 631 – 941 (ISO) or 1250 – 1521 (CI) μg/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
470 ± 280 (ISO) or 1400 ± 200 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
Acrolein (107-02-8) 2A Inade. Suffic. 128 2021 × 7.8 – 20.0 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012) <56 ng/g in unheated waterpipe tobacco solid waste (Hsieh et al., 2021)
Present (Oldham et al., 2014)
24.9 – 48.5 (ISO) or 100.0 – 120.7 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
106 – 144 (CI) μg/cig in U.S. commercial cigarettes (Ding et al., 2016)
8.6 – 62.7 (ISO) or 82.9 – 110 (CI) μg/cig in SPECTRUM research cigarettes (Ding et al., 2017)
30.8 – 105 (ISO) or 105 – 213 (CI) μg/unit in 15 sheet-wrapped cigars and 35 cigarettes from the U.S. market (Cecil et al., 2017)
21 – 64 (ISO) or 103 – 158 (CI) μg/cig in 13 Natural American Spirit cigarettes and 49 – 60 (ISO) or 100 – 162 (CI) μg/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
55 ± 37 (ISO) or 230 ± 40 (CI) μg/g (mean ± SD) in Dutch commercial cigarettes (Pennings et al., 2020)
24.9 – 223 μg/cig (International Agency for Research on Cancer, 2021a)
Crotonaldehyde ((E/Z), 4170-30-3) 2B Inade. Limited 128 2021 × 2.0 – 4.7 (modified ISO) μg/cig in 10 Spanish brands (Marcilla et al., 2012) Present (Oldham et al., 2014)
Present (Oldham et al., 2014)
4.8 – 12.1 (ISO) or 37.9 – 47.1 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
0.86 – 17.45 (ISO) or 29.2 – 52.7 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
25 – 72 (CI) μg/cig in U.S. commercial cigarettes (Ding et al., 2016)
3.9 – 20.3 (ISO) or 34.0 – 99.5 (CI) μg/cig in SPECTRUM research cigarettes (Ding et al., 2017)
11 – 36 (ISO) or 20 – 52 (CI) μg/cig in 13 Natural American Spirit cigarettes and 13 – 31 (ISO) or 41 – 63 (CI) μg/cig in 5 U.S. popular cigarette brands (Jain et al., 2019)
19.79 μg/cig (mean value) in Chinese cigarettes (Cai et al., 2019)
Halogenated compounds (2 compounds)
Vinyl chloride (75-01-4) 1 Suffic. Suffic. 100F 2012 × × nd – 36.6 ng/cig (Hecht, 2012)
<0.005 – 0.042 (ISO) or 0.046 – 0.098 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
2,3,4,7,8-Pentachlorodibenzofuran (2,3,4,7,8-PeCDF, 57117-31-4) 1 ND Suffic. 100F 2012 × Detectable (Oldham et al., 2014)
Nitro compounds (3 compounds)
Nitromethane (75-52-5) 2B ND Suffic. 77 2000 × × 0.13 – 2.3 (ISO) μg/cig in 10 Chinese cigarette brands (Wang et al., 2015)
0.27 – 3.26 (ISO) or 2.13 – 7.66 (CI) μg/cig in 50 U.S. brands (Pazo et al., 2016)
1.6 – 4.9 (modified ISO) or 3.2 – 12 (CI) μg/cig in 10 U.S. popular cigarettes (Junco et al., 2021)
2-Nitropropane (79-46-9) 2B Inade. Suffic. 71 1999 × × nd – 18.7 μg/cig (Hecht, 2012)
Barely detectable (Oldham et al., 2014)
0.18 – 1.5 (ISO) μg/cig in 10 Chinese cigarette brands (Wang et al., 2015)
Nitrobenzene (98-95-3) 2B Inade. Suffic. 65 1996 × × 18 – 38 ng/cig in 13 U.S. popular cigarettes (Chapman et al., 2018)
Phenolic compounds (2 compounds)
Catechol (120-80-9) 2B ND Suffic. 71 1999 × × 5.1 – 89.9 μg/cig (Hecht, 2012) <0.7 – 50.5 μg/g in unheated waterpipe tobacco solid waste (Hsieh et al., 2021)
22.7 – 51.1 (ISO) or 49.6 – 118 (CI) μg/cig in 10 cigarette brands (Wu et al., 2012a)
Present (Oldham et al., 2014)
25.0 – 54.8 (ISO) and 86.3 – 137.0 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
Caffeic acid (331-39-5) 2B ND Suffic. 56 1993 × × Detectable (Oldham et al., 2014)
Miscellaneous compounds (5 compounds)
Acetamide (60-35-5) 2B ND Suffic. 71 1999 × × 2.2 – 111 μg/cig (Hecht, 2012)
Present (Oldham et al., 2014)
Acrylamide (79-06-1) 2A Inade. Suffic. 60 1994 × × 2.3 μg/cig (Hecht, 2012)
Present (Oldham et al., 2014)
Ethyl carbamate (51-79-6) 2A Inade. Suffic. 96 2010 × × 10 – 35 ng/cig (Hecht, 2012) Barely detectable (Oldham et al., 2014)
Barely detectable (Oldham et al., 2014)
Vinyl acetate (108-05-4) 2B Inade. Limited 63 1995 × × 1.6 – 4 μg/cig (Hecht, 2012)
Present (Oldham et al., 2014)
0.056 – 0.497 (ISO) or 0.670 – 1.272 (CI) μg/cig in 50 U.S. cigarette brands (Pazo et al., 2016)
Acrylonitrile (107-13-1) 2B Inade. Suffic. 71 1999 × × 0.9 – 19.6 μg/cig (Hecht, 2012)
Present (Oldham et al., 2014)
6.1 – 12.6 (ISO) and 32.4 – 37.4 (CI) μg/cig in 3 commercial brands (Eldridge et al., 2015)
0.90 – 15.34 μg/cig (ISO); 19.7 – 37.7 μg/cig (CI) in 50 U.S. brands (Pazo et al., 2016)
28 ± 3.6 (ISO) or 69 ± 6.6 (CI) μg/little cigar (mean ± SD) in 60 U.S. brands (Vu et al., 2021)
Inorganic compounds (8 compounds)
Arsenic 1 Suffic. Suffic. 100C 2012 × × Present (Oldham et al., 2014) 0.22 – 0.36 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<0.5 – 5.8 (ISO) or 5.7 – 15.2 (CI) ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) Present (Oldham et al., 2014)
<2.7 – 2.8 (ISO) or <8.8 – 9.6 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.12 – 0.66 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
0.105 – 0.177 μg/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
0.48 – 0.64 μg/g in 13 Natural American Spirit cigarettes and 0.42 – 0.67 μg/g in 5 U.S. popular cigarette brands (Jain et al., 2019)
Beryllium 1 Suffic. Suffic. 100C 2012 × × nd – 0.5 ng (Hecht, 2012) 0.015 – 0.049 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
Barely detectable (Oldham et al., 2014) Detectable (Oldham et al., 2014)
0.020 – 0.075 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
13 – 20 ng/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
Cadmium 1 Suffic. Suffic. 100C 2012 × × Present (Oldham et al., 2014) 1.0 – 1.7 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<5.0 – 80 (ISO) and 81 – 200 ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) Present [Oldham et al, 2014](Oldham et al., 2014)
13.2 – 30.0 (ISO) and 77.8 – 96.7 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.752 – 1.69 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
0.91 – 1.11 μg/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
0.90 – 1.74 μg/g in 13 Natural American Spirit cigarettes and 1.01 – 1.11 μg/g in 5 U.S. popular cigarette brands (Jain et al., 2019)
Chromium(VI) 1 Suffic. Suffic. 100C 2012 × × Barely detectable (Oldham et al., 2014) 1.4 – 3.1 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<0.88 (ISO) or <1.1 (CI) ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) Present (Oldham et al., 2014)
<3.7 (ISO) or <14.0 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.88 – 6.46 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
0.6 – 1.03 ng/cig in U.S. commercial cigarettes (Fresquez et al., 2017) 0.89 – 1.34 μg/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
0.42 – 0.95 μg/g in 13 Natural American Spirit cigarettes and 1.07 – 2.15 μg/g in 5 U.S. popular cigarette brands (Jain et al., 2019)
Cobalt 2B Inade. Suffic./limited/Inade. 52 1991 × × Barely detectable (Oldham et al., 2014) 0.44 – 1.11 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<0.025 – 0.151 (ISO) or 0.09 – 0.30 (CI) ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) 0.65 – 1.00 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
0.36 – 0.58 μg/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
Lead (inorganic) 2A Limited Suffic. 87 2006 × × Present (Oldham et al., 2014) 0.60 – 1.16 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<5.0 – 23 (ISO) or 29 – 58 (CI) ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) Present (Oldham et al., 2014)
<10.3 – 12.7 (ISO) or 26.3 – 33.3 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 0.40 – 0.82 μg/g in the tobacco of SPECTRUM cigarettes (Richter et al., 2016)
0.59 – 0.78 μg/g in 13 Natural American Spirit cigarettes and 0.66 – 1.03 μg/g in 5 U.S. popular cigarette brands (Jain et al., 2019)
Nickel 1 Suffic. Suffic. 100C 2012 × × Present (Oldham et al., 2014) 2.1 – 3.9 μg/g dry weight in the tobacco of 50 U.S. cigarette brands (Fresquez et al., 2013)
<0.38 – 0.48 (ISO) or < 0.50 – 1.09 (CI) ng/cig in 50 U.S. cigarette brands (Pappas et al., 2014) Present (Oldham et al., 2014)
<30.9 (ISO) and <25.5 (CI) ng/cig in 3 commercial brands (Eldridge et al., 2015) 1.58 – 4.37 μg/g dry weight in the tobacco of 17 U.S. litter cigar brands (Pappas et al., 2015)
1.35 – 1.79 μg/g in SPECTRUM cigarettes (Richter et al., 2016)
0.56 – 1.65 μg/g in 13 Natural American Spirit cigarettes and 2.11 – 3.24 μg/g in 5 U.S. popular cigarette brands (Jain et al., 2019)
Polonium-210 1 Inade. Suffic. 78 2001 × × 0.03 – 1.0 pCi/cig (Hecht, 2012) Present (Oldham et al., 2014)
Present (Oldham et al., 2014)
a

ND: no adequate data; Inade.: inadequate evidence; Limited: limited evidence; Suffic.: sufficient evidence.

b

Hecht, SS. Nicotine Tob. Res. 2012, 14 (1), 18.

c

In the U.S. FDA list of harmful and potentially harmful constitutes in tobacco and tobacco smoke, a total of 79 carcinogens is included. However, some compounds including 1-aminonaphthalene (group 3), dibenzo[a,e]pyrene (also in the Hecht list, group 3), mercury and inorganic mercury compounds (group 3) are not considered carcinogenic to humans by IARC. The compounds cresols and uranium-235 and -238 have not been classified. Aflatoxin B1 is generally considered as the contaminant from the preparation and storage of tobacco products.

d

ISO: ISO 3308 non-intense smoking regimen; CI: ISO 20778 Canadian intense smoking regimen.

e

nd: not detected.

f

For the description of the reported detection of tobacco carcinogens by Oldham et al, 2014, Regul. Toxicol. Pharmacol. 70 (1), 138 – 148: “Present” indicates the analyte levels were above limit of quantitation in multiple batches of samples; “Detectable” indicates the analyte levels were less than limit of quantitation in at least some batches of samples; “Barely detectable” indicates the analyte levels were less than limit of detection.