Table 1.
HPHC yields and associated biomarkers of exposure reported in four clinical studies.
| HPHC [Organ class toxicity1] | 3R4F2 | THS2.2 FR12 | THS2.2 FR1 M2 | Biomarker of Exposure [Matrix] | |
|---|---|---|---|---|---|
| 1 | 1,3-butadiene [CA, RT, RDT] | 63.8 ± 3.5 μg/stick | 0.294 ± 0.042 μg/stick | 0.265 ± 0.024 μg/stick | Monohydroxybutenylmercapturic acid (MHBMA) [Urine] |
| 2 | 1-aminonaphthalene [CA] | 20.8 ± 1.3 ng/stick | 0.077 ng/stick | 0.086 ng/stick | 1-Aminonaphthalene (1-NA) [Urine] |
| 3 | 2-aminonaphthalene [CA] | 11.0 ± 0.6 ng/stick | 0.046 ± 0.008 ng/stick | <0.035 ng/stick | 2-Aminonaphthalene (2-NA) [Urine] |
| 4 | 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) [CA] | 266 ± 15 ng/stick | 6.7 ± 0.6 ng/stick | 5.9 ± 0.4 ng/stick | Total 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol (total NNAL) [Urine] |
| 5 | 4-aminobiphenyl [CA] | 3.26 ± 0.12 ng/stick | <0.051 ng/stick | <0.051 ng/stick | 4-Aminobiphenyl (4-ABP) [Urine] |
| 6 | Acrolein [RT, CT] | 154 ± 20 μg/stick | 11.30 ± 2.36 μg/stick | 9.15 ± 0.43 μg/stick | 3-Hydroxypropyl- mercapturic acid (3-HPMA) [Urine] |
| 7 | Acrylonitrile [CA, RT] | 31.9 ± 1.8 μg/stick | 0.258 ± 0.041 μg/stick | 0.220 ± 0.014 μg/stick | 2-Cyanoethyl Mercapturic acid (CEMA) [Urine] |
| 8 | Benzene [CA, CT, RDT] | 97.6 ± 4.7 μg/stick | 0.649 ± 0.074 μg/stick | 0.640 ± 0.040 μg/stick | S-Phenyl-mercapturic acid (S-PMA) [Urine] |
| 9 | Benzo[a]pyrene [CA] | 14.2 ± 0.3 ng/stick | <1.00 ng/stick | 1.29 ± 0.10 ng/stick | Total 3-Hydroxy Benzopyrene (3-OH-B[a]P)[Urine] |
| 10 | Carbon monoxide [RDT, CT] | 32.8 ± 2.4 mg/stick | 0.531 ± 0.068 mg/stick | 0.594 ± 0.110 mg/stick | Carboxyhemoglobin (COHb) [Blood] |
| 11 | Crotonaldehyde [CA] | 68.8 ± 14.4 μg/stick | 4.14 ± 0.23 μg/stick | 3.24 ± 0.21 μg/stick | 3-Hydroxy-1-methyl propyl-mercapturic acid (3-HMPMA) [Urine] |
| 12 | Ethylene oxide [CA, RT, RDT] | 29.4 ± 2.0 μg/stick | 0.201 ± 0.014 μg/stick | 0.202 ± 0.013 μg/stick | 2-Hydroxyethyl-mercapturic acid (HEMA) [Urine] |
| 13 | N-nitrosonornicotine (NNN) [CA] | 309 ± 41 ng/stick | 17.2 ± 1.25 ng/stick | 13.7 ± 1.21 ng/stick | Total N-nitrosonornicotine (total NNN) [Urine] |
| 14 | o-toluidine [CA] | 85.5 ± 2.7 ng/stick | 1.260 ± 0.18 ng/stick | 0.777 ± 0.287 ng/stick | o-Toluidine (o-tol) [Urine] |
| 15 | Pyrene [Indicator of CA substances] | 87.3 ± 2.5 ng/stick | <5.00 ng/stick | 9.06 ± 0.68 ng/stick | Total 1-hydroxypyrene (1-OHP) [Urine] |
All markers were measured in 24h urine, with the exception of carboxyhemoglobin which was measured in blood samples. Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was determined as the molar sum of 4-(methylnitrosamino)-1-(3-pyridy1)-1-butanol and its O-glucuronide conjugate and Total 1-hydroxypyrene was determined as the molar sum of 1-hydroxypyrene and its glucuronide and sulfate conjugates. HPHC yields from 3R4F and THS 2.2 FR1 were obtained under HCI machine-smoking conditions and expressed on a per-cigarette/tobacco stick basis.
3R4F = Reference combustible cigarette from University of Kentucky, AD = addictive, CA = carcinogen, CT = cardiovascular toxicant, RT = respiratory toxicant, RDT = reproductive and developmental toxicant, THS2.2 FR1 = THS 2.2 heatsticks, THS2.2 FR1 M = mentholated version of THS2.2 FR1.
1Organ class toxicities from FDA list of HPHCs (US Food and Drug Administration, 2012).
2Analyte yields from THS2.2 FR1, THS2.2 FR1 M, and 3R4F obtained under HCI machine-smoking conditions and expressed on a per-cigarette/tobacco stick basis published in Schaller et al. (2016a).