Table 2.
Biomarkers of exposure to nicotine and selected toxicants in urine of exclusive E-cigarette users (n = 124) from US, UK and Poland (normalized for creatinine; geometric means, 95% confidence intervals).
| Parent Compound | Biomarker | US (n = 48) |
UK (n = 36) | Poland (n = 40) | p-Value |
|---|---|---|---|---|---|
| Nicotine Metabolites (ng/mg creatinine) | |||||
| Nicotine | Nicotine Equivalence (nmol/mg) |
35.81
c
(24.98–51.33) |
27.36
c
(17.85–41.92) |
81.34
a,b
(54.47–121.45) |
0.002 |
| trans-3′-Hydroxycotinine (HCTT) |
3239.25
(2208.17–4751.76) |
2334.34
c
(1482.06–3676.73) |
7273.45
a,b
(4747.35–11143.70) |
0.002 | |
| Cotinine (COTT) |
1710.08
c
(1191.35–2454.66) |
1331.44
c
(867.38–2043.79) |
3882.26
a,b
(2595.98–5805.89) |
0.002 | |
| Nicotine (NICT) |
457.22
c
(316.74–659.98) |
422.20
c
(273.22–652.41) |
1205.23
a,b
(800.89–1813.69) |
0.001 | |
| Cotinine N-oxide (COXT) |
214.18
c
(147.90–310.15) |
150.78
c
(97.20–233.87) |
459.79
a,b
(304.46–694.37) |
0.002 | |
| Nicotine 1′-oxide (NOXT) |
430.34
c
(289.21–640.33) |
403.70
c
(252.01–646.69) |
1209.91
a,b
(777.28–1883.36) |
0.001 | |
| Norcotinine (NCTT) |
48.70
c
(34.46–68.83) |
29.64
c
(19.66–44.67) |
94.29
a,b
(64.14–138.59) |
0.001 | |
| Nornicotine (NNCT) |
27.57
c
(20.56–36.98) |
18.10
c
(12.78–25.63) |
67.00
a,b
(48.32–92.89) |
<0.001 | |
| Minor Tobacco Alkaloids (ng/mg creatinine) | |||||
| Anabasine (ANBT) | Anabasine (ANBT) |
1.33
c
(0.93–1.89) |
1.08
c
(0.71–1.63) |
4.66
a,b
(3.15–6.87) |
<0.001 |
| Anatabine (ANTT) | Anatabine (ANTT) |
0.76
c
(0.49–1.15) |
0.81
c
(0.48–1.34) |
2.46
a,b
(1.53–3.94) |
0.001 |
| Tobacco-Specific Nitrosamines (TSNAs) (pg/mg creatinine) | |||||
| 4-methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK) | 4-methylnitrosamino)-4-(3-pyridyl)-1-butanol (NNAL) |
5.14 b
(3.63–7.26) |
1.74
a,c
(1.15–2.62) |
4.82
b
(3.26–7.12) |
<0.001 |
| N’-nitrosoanabasine (NAB) | N’-nitrosoanabasine (NAB) |
1.7 (1.35–2.26) |
1.17 (0.85–1.58) |
1.55 (1.16–2.08) |
0.157 |
| N’-nitrosoanatabine (NAT) | N’-nitrosoanatabine (NAT) |
3.50 (2.65–4.63) |
2.97 2.14–4.13) |
4.43 (3.24–6.06) |
0.257 |
| Volatile Organic Compounds (VOCs) (ng/mg creatinine) | |||||
| Acrolein | N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA) |
218.91
c
(171.19–279.91) |
169.18
c
(126.40–226.42) |
436.59
a,b
(332.04–574.05) |
<0.001 |
| N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) |
79.04
c
(62.68–99.68) |
53.45
c
(40.59–70.37) |
156.82
a,b
(121.11–203.04) |
<0.001 | |
| Acrylamide | N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) |
47.49
b
(37.08–60.81) |
27.33
a
(20.38–36.64) |
38.46
(29.20–50.65) |
0.026 |
| N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) |
15.17
b,c
(12.08–19.04) |
9.52
a
(7.27–12.46) |
9.62
a
(7.46–12.38) |
0.012 | |
| Acrylonitrile | N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA) |
3.75
b
(2.51–5.58) |
1.38
a
(0.85–2.21) |
2.90
(1.86–4.52) |
0.009 |
| Benzene | N-Acetyl-S-(phenyl)-L-cysteine (PMA) |
0.77
c
(0.61–0.95) |
0.75
(0.57–0.97) |
1.14
a
(0.89–1.46) |
0.035 |
| 1,3-Butadiene | N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (MHBMA3) |
5.22
c
(3.97–6.85) |
4.30
c
(3.11–5.93) |
10.11
a,b
(7.46–13.69) |
<0.001 |
| N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA) |
206.14
c
(170.16–249.72) |
151.88
c
(120.99–190.66) |
392.56
a,b
(317.08–486.01) |
<0.001 | |
| Crotonaldehyde | N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA) |
251.95
c
(203.88–311.34) |
227.82
c
(177.26–292.81) |
421.77
a,b
(333.21–533.85) |
0.002 |
| Cyanide | 2-Aminothiazoline-4-carboxylic acid (ATCA) |
67.46
c
(50.60–89.92) |
66.54
c
(47.32–93.56) |
121.85
a,b
(88.48–167.81) |
0.017 |
| N,N-Dimethylformamide; methyl isocyanate | N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) |
160.50
b
(128.50–200.45) |
61.50
a,c
(47.24–80.04) |
224.10
b
(174.96–287.03) |
<0.001 |
| Ethylene oxide; acrylonitrile; vinyl chloride | N-Acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA) *** |
0.55 (0.44–0.69) |
0.44 (0.33–0.57) |
0.50 (0.39–0.64) |
0.442 |
| Propylene oxide | N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) |
39.34 (30.11–51.41) |
31.51 (22.94–43.26) |
40.75 (30.25–54.89) |
0.491 |
| Styrene | Mandelic acid (MA) |
98.37 (79.67–121.45) |
102.37 (79.73–131.43) |
134.56 (106.41–170.15) |
0.144 |
| Styrene; ethylbenzene | Phenylglyoxylic acid (PGA) |
100.57
c
(79.01–128.01) |
72.03
c
(54.11–95.88) |
160.44
a,b
(122.64–209.88) |
0.001 |
| Toluene; benzyl alcohol | N-Acetyl-S-(benzyl)-L-cysteine (BMA) |
4.14 (3.18–5.36) |
4.84 (3.55–6.61) |
5.78 (4.31–7.74) |
0.266 |
| Xylene | 2-Methylhippuric acid (2MHA) |
17.66 (13.49–23.11) |
10.75 (7.81–14.78) |
16.73 (12.40–22.58) |
0.063 |
| 3- + 4-Methylhippuric acids (34MHA) |
134.38
b
(103.81–173.94) |
50.29
a,c
(37.03–68.29) |
97.28
b
(72.98–129.66) |
<0.001 | |
Note: Bolded values denote statistically significant differences in geometric mean concentrations between at least two of the countries. a indicates statistically significant difference from the US; b indicates statistically difference from the UK; c indicates statistically significant difference from Poland (all p < 0.05). Reported p-values indicate findings from omnibus statistic; superscript letter notation reflects significant findings adjusted for multiple comparisons (sidak). Geometric means are adjusted for urinary creatinine, age, sex, and race. ***: These analytes had more than 40% of measured values fall below the analytical limit of detection (LOD).