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Assessment of the Nicotine Pharmacokinetics When Using Two Types of E-Cigarettes in Healthy Adults Who Smoke: Results From Two Randomized, Crossover Studies Cover

Assessment of the Nicotine Pharmacokinetics When Using Two Types of E-Cigarettes in Healthy Adults Who Smoke: Results From Two Randomized, Crossover Studies

Contributions to Tobacco & Nicotine Research
Volume 33 (2024): Issue 3 (June 2024)
By: ,  ,  ,  ,   and    
Open Access
|Aug 2024
Figures & tables

Figures & Tables

Table 1.

Study product characteristics.

StudyProductShort codeArticleBrandCategoryDevice typeFlavorNicotine content of e-liquid (%)Regimen
Study 1AeDNC1.0aTestLogic PowerE-cigaretteCig-a-likeTobacco2.4%(w/w)ad libitum, 5 min use
BeDNC1.0aTestLogic PowerE-cigaretteCig-a-likeCherry2.4% (w/w)ad libitum, 5 min use
CeDNC1.0aTestLogic PowerE-cigaretteCig-a-likeMenthol2.4% (w/w)ad libitum, 5 min use
DCCComparatorN/ACigaretteN/AN/AN/Aad libitum, one cigarette (up to 5 min)
ENicotine gumBenchmarkNicorette® Gum, White Ice Mint, 2 mgNicotine gumN/AN/AN/Aad libitum, 30 min use
FReference e-cigaretteBenchmarkblu PLUS+E-cigaretteCig-a-likeTobacco2.4% (w/w)ad libitum, 5 min use
Study 2AeDNC2.0aTestLogic ProE-cigaretteClosed tankTobacco1.80%(w/w)ad libitum, 5 min use
BeDNC2.0aTestLogic ProE-cigaretteClosed tankMenthol1.80% (w/w)ad libitum, 5 min use
CeDNC2.0aTestLogic ProE-cigaretteClosed tankCherry1.49% (w/w)ad libitum, 5 min use
DeDNC2.0aTestLogic ProE-cigaretteClosed tankBerry Mint1.49% (w/w)ad libitum, 5 min use
ECCComparatorN/ACigaretteN/AN/AN/Aad libitum, one cigarette (up to 5 min)
FNicotine inhalerBenchmarkNicotrol®Inhaler, 10 mg per cartridgeNicotine inhalerN/AN/AN/Aad libitum, 20 min use
GReference e-cigaretteBenchmarkVuse VibeE-cigaretteClosed tankTobacco3.0% (w/w)ad libitum, 5 min use

[i] Abbreviations: CC = combustible cigarettes; eDNC1.0a = electronic direct nicotine heating system platform 1 generation 0 version a; eDNC2.0a = electronic direct nicotine heating system platform 2 generation 0 version a; N/A = not applicable.

Table 2.

Demographic characteristics by study group, Study 1.

AFBECDBACFDECBDAEFDCEBFAEDFCABFEADBCTOTAL
(N = 9)(N = 10)(N = 9)(N = 8)(N = 9)(N = 7)(N = 52)
Sex
Male, n (%)5 (55.6%)5 (50.0%)7 (77.8%)4 (50.0%)6 (66.7%)4 (57.1%)31 (59.6%)
Female, n (%)4 (44.4%)5 (50.0%)2 (22.2%)4 (50.0%)3 (33.3%)3 (42.9%)21 (40.4%)
Age, years Mean (SD)40.6 (9.17)37.9 (10.19)40.8 (7.90)44.5 (8.73)38.0 (11.91)39.7 (9.23)40.1 (9.43)
Race
White, n (%)9 (100.0%)8 (80.0%)9 (100.0%)6 (75.0%)7 (77.8%)5 (71.4%)44 (84.6%)
African American, n (%)0 (0.0%)2 (20.0%)0 (0.0%)2 (25.0%)2 (22.2%)2 (28.6%)8 (15.4%)
Other, n (%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)
BMI, kg/m2 Mean (SD)27.0 (4.55)24.9 (2.61)27.3 (4.23)24.9 (2.75) 24.8(3.46)25.3 (2.36)25.7 (3.45)
CPD, Mean (SD)15.9 (4.70)18.8 (5.47)18.6 (6.23)17.6 (3.50) 18.8(8.45)15.3 (4.72)17.6 (5.68)
Regular smoking flavor
Non-menthol, n (%)5 (55.6%)6 (60.0%)7 (77.8%)5 (62.5%)3 (33.3%)3 (42.9%)29 (55.8%)
Menthol, n (%)4 (44.4%)4 (40.0%)2 (22.2%)3 (37.5%)6 (66.7%)4 (57.1%)23 (44.2%)
FTCD, Mean (SD)3.9 (0.93)5.3 (1.42)5.2 (1.39)5.0 (1.77)4.8 (1.72)5.0 (2.00)4.9 (1.55)

[i] Abbreviations: BMI = body mass index; CPD = cigarettes per day; FTCD = Fagerström Test for Cigarette Dependence; SD = standard deviation;

[ii] Products: Product A = eDNC1.0a, Tobacco flavor; Product B = eDNC1.0a, Cherry flavor; Product C = eDNC1.0a, Menthol flavor; Product D = Usual brand of combustible cigarettes; Product E = Nicotine gum; Product F = reference e-cigarette.

Table 2.

Demographic characteristics by study group, Study 1.

AFBECDBACFDECBDAEFDCEBFAEDFCABFEADBCTOTAL
(N = 9)(N = 10)(N = 9)(N = 8)(N = 9)(N = 7)(N = 52)
Sex
Male, n (%)5 (55.6%)5 (50.0%)7 (77.8%)4 (50.0%)6 (66.7%)4 (57.1%)31 (59.6%)
Female, n (%)4 (44.4%)5 (50.0%)2 (22.2%)4 (50.0%)3 (33.3%)3 (42.9%)21 (40.4%)
Age, years Mean (SD)40.6 (9.17)37.9 (10.19)40.8 (7.90)44.5 (8.73)38.0 (11.91)39.7 (9.23)40.1 (9.43)
Race
White, n (%)9 (100.0%)8 (80.0%)9 (100.0%)6 (75.0%)7 (77.8%)5 (71.4%)44 (84.6%)
African American, n (%)0 (0.0%)2 (20.0%)0 (0.0%)2 (25.0%)2 (22.2%)2 (28.6%)8 (15.4%)
Other, n (%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)
BMI, kg/m2 Mean (SD)27.0 (4.55)24.9 (2.61)27.3 (4.23)24.9 (2.75)24.8 (3.46)25.3 (2.36)25.7 (3.45)
CPD, Mean (SD)15.9 (4.70)18.8 (5.47)18.6 (6.23)17.6 (3.50)18.8 (8.45)15.3 (4.72)17.6 (5.68)
Regular smoking flavor
Non-menthol, n (%)5 (55.6%)6 (60.0%)7 (77.8%)5 (62.5%)3 (33.3%)3 (42.9%)29 (55.8%)
Menthol, n (%)4 (44.4%)4 (40.0%)2 (22.2%)3 (37.5%)6 (66.7%)4 (57.1%)23 (44.2%)
FTCD, Mean (SD)3.9 (0.93)5.3 (1.42)5.2 (1.39)5.0 (1.77)4.8 (1.72)5.0 (2.00)4.9 (1.55)

[i] Abbreviations: BMI = body mass index; CPD = cigarettes per day; FTCD = Fagerström Test for Cigarette Dependence; SD = standard deviation;

[ii] Products: Product A = eDNC1.0a, Tobacco flavor; Product B = eDNC1.0a, Cherry flavor; Product C = eDNC1.0a, Menthol flavor; Product D = Usual brand of combustible cigarettes; Product E = Nicotine gum; Product F = reference e-cigarette.

Figure 1.

Mean plasma nicotine concentration profiles in Study 1. Error bars correspond to standard error.

Table 3.

Summary of the pharmacokinetic parameters for nicotine, Study 1.

Product AProduct BProduct CProduct DProduct EProduct F
eDNC1.0a Tobacco flavoreDNC1.0a Cherry flavoreDNC1.0a Menthol flavorUsual brand of combustible cigarettesNicotine gumReference e-cigarette
Parameter(n = 52)(n = 52)(n = 52)(n = 52)(n = 52)(n = 52)
Cmax (ng/mL)
Geometric LS mean (95% CI) a3.71 (3.15, 4.37) b3.44 (2.92, 4.05) b4.18 (3.55, 4.92) b15.32 (13.00, 18.04)3.26 (2.77, 3.85)2.90 (2.46, 3.42)
Min, Max0.72, 17.200.65, 11.301.41, 13.505.52, 42.800.87, 10.100.66, 11.40
AUC0–last (ng × hr/mL)
Geometric LS mean (95% CI) a6.24 (5.37, 7.25) b5.62 (4.84, 6.54) b7.04 (6.06, 8.18) b21.09 (18.15, 24.52)8.21 (7.06, 9.54)4.64 (3.99, 5.39)
Min, Max0.92, 20.670.99, 14.532.22, 21.505.25, 45.331.98, 15.680.80, 12.77
Tmax (min)
Median15.015.015.07.145.215.0
Min, Max5.0, 60.07.0, 45.05.0, 60.03.0, 45.030.0, 90.05.0, 60.0
Amount of e-liquid used (mg)
Mean (SD)31.5 (16.31)29.6 (13.25)35.0 (19.44)N/AN/A28.2 (16.77)
Min, Max8.0, 73.77.1, 64.410.2, 104.25.9, 73.9
Estimated nicotine consumption (mg)
Mean (SD)0.75 (0.391)0.71 (0.318)0.84 (0.467)N/AN/A0.68 (0.402)
Min, Max0.19, 1.770.17, 1.550.24, 2.500.14, 1.77

a Geometric LS means were evaluated separately in a linear mixed-effects analysis of variance (ANOVA) model with fixed effects for period, sequence, product, and a random effect for subject nested within sequence.

b Significantly different from usual brand of combustible cigarettes (Product D); p < 0.05.

Abbreviations: SD = standard deviation; CI = confidential interval; N/A = not applicable; LS = least square.

Table 4.

Summary of the subjective effects measures, Study 1.

ParameterProduct AProduct BProduct CProduct DProduct EProduct F
eDNC1.0a Tobacco flavoreDNC1.0a Cherry flavoreDNC1.0a Menthol flavorUsual brand of combustible cigarettesNicotine gumReference e-cigarette
(n = 52)(n = 52)(n = 52)(n = 52)(n = 52)(n = 52)
Product liking VAS a
Emax – Mean (SD)54.5 (34.44)53.4 (30.32)56.7 (33.03)83.1 (22.80)52.0 (31.60)57.8 (31.58)
> 50 to 100 mm – n (%)32 (61.5%)32 (61.5%)33 (63.5%)47 (90.4%)30 (57.7%)36 (69.2%)
Intent to use the product again VAS b
Emax – Mean (SD)55.1 (33.70)49.3 (31.22)52.7 (36.15)90.4 (17.37)46.2 (36.19)54.2 (33.20)
> 50 to 100 mm – n (%)36 (69.2%)31 (59.6%)32 (61.5%)51 (98.1%)29 (55.8%)31 (59.6%)
mPES, subscales c
Satisfaction – Mean (SD)3.4 (1.74)3.4 (1.55)3.7 (1.79)5.3 (1.56)3.5 (1.76)3.6 (1.58)
Psychological reward – Mean (SD)2.8 (1.49)2.8 (1.37)2.8 (1.35)3.9 (1.67)2.7 (1.67)2.7 (1.42)
Aversion – Mean (SD)1.4 (0.59)1.3 (0.41)1.4 (0.74)2.1 (1.18)1.4 (0.77)1.2 (0.47)
Relief – Mean (SD)3.7 (2.15)4.0 (2.00)3.9 (1.86)5.5 (2.02)3.0 (1.91)4.0 (1.75)

a Product liking VAS questionnaire (“Do you like the product effect?”) rating scales with “Not at all (0 mm)” to “Extremely (100 mm)”.

b Intent to use product again VAS questionnaire (“If given the opportunity, would you use this product again?”) rating scales with “Definitely would not (0 mm)”, “Don’t care (50 mm)”, to “Definitely would (100 mm)”.

c The subscales of modified Product Evaluation Scale (mPES):

  • Satisfaction = average score from 4 questions (“Was it satisfying?”, “Did it taste good?”, “Did you enjoy the sensations in your mouth?” and “Did you enjoy it?”);

  • Psychological reward = average scores from 5 questions (“Did it calm you down?”, “Did it make you feel more awake?”, “Did it make you feel less irritable?”, “Did it help you concentrate?”, and “Did it reduce your hunger for food?”);

  • Aversion = average score from 2 questions (“Did it make you dizzy?” and “Did it make you nauseous?”);

  • Relief = score from a question (“Did it immediately relieve your craving for a cigarette?”). Each item was rated on a 7-point Likert scale ranging from 1 (“Not at all”) to 7 (“Extremely”).

Abbreviations: SD = standard deviation; mPES = modified Product Evaluation Scale; VAS = visual analog scale.

Table 5.

Demographic characteristics by study group, Study 2.

ABGCFDEAGBFCEDBACGDFEBCADGEFCBDAEGFCDBEAFGDCEBFAGDECFBGAEDFCGBAEFDGCABFEGDACBFGEADBCGAFBECDGFAEBDCTOTAL
(N= 3)(N= 2)(N= 4)(N= 4)(N= 3)(N= 4)(N= 3)(N= 4)(N= 4)(N= 4)(N= 4)(N= 4)(N= 4)(N= 4)(N= 51)
Sex
Male, n(%)3 (100.0%)2 (100.0%)3 (75.0%)2 (50.0%)2 (66.7%)4 (100.0%)2 (66.7%)2 (50.0%)1 (25.0%)3 (75.0%)1 (25.0%)3 (75.0%)3 (75.0%)2 (50.0%)33 (64.7%)
Female, n (%)0 (0.0%)0 (0.0%)1 (25.0%)2 (50.0%)1 (33.3%)0 (0.0%)1 (33.3%)2 (50.0%)3 (75.0%)1 (25.0%)3 (75.0%)1 (25.0%)1 (25.0%)2 (50.0%)18 (35.3%)
Age, years, Mean (SD)27.3 (5.13)26.5 (0.71)41.0 (13.44)28.0 (2.16)39.3 (10.60)39.0 (11.60)29.7 (8.62)43.3 (9.43)31.8 (10.05)39.0 (4.97)41.8 (14.59)45.8 (15.95)46.8 (11.21)42.3 (10.69)38.0 (11.27)
Race
White,n (%)2 (66.7%)2 (100.0%)2 (50.0%)4 (100.0%)3 (100.0%)4 (100.0%)1 (33.3%)4 (100.0%)3 (75%)4 (100.0%)3 (75.0%)4 (100.0%)4 (100.0%)4 (100.0%)44 (86.3%)
African American, n (%)0 (0.0%)0 (0.0%)2 (50.0%)0 (0.0%)0 (0.0%)0 (0.0%)2 (66.7%)0 (0.0%)1 (25%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)5 (9.8%)
Other, n (%)1 (33.3%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)0 (0.0%)1 (25.0%)0 (0.0%)0 (0.0%)0 (0.0%)2 (3.9%)
BMI, kg/m2Mean (SD)23.3 (3.59)31.6 (3.01)28.6 (4.52)24.8 (2.27)28.4 (2.13)29.9 (5.75)25.8 (6.08)27.8 (3.45)25.7 (5.51)28.5 (5.06)23.7 (3.52)27.3 (3.10)27.8 (3.76)26.1 (6.05)27.0 (4.33)
CPD, Mean (SD)17.3 (4.62)20.0 (0.00)15.5 (5.26)13.8 (4.79)14.0 (5.29)17.5 (5.00)12.0 (2.65)18.8 (8.54)11.5 (2.38)17.5 (2.89)20.0 (0.00)13.5 (4.43)17.5 (2.89)19.5 (1.00)16.3 (4.64)
Regular smoking flavor
Non-menthol, n (%)3 (100.0%)0 (0.0%)0 (0.0%)2 (50.0%)1 (33.3%)2 (50.0%)0 (0.0%)2 (50.0%)3 (75.0%)4 (100.0%)3 (75.0%)1 (25.0%)2 (50.0%)4 (100.0%)27 (52.9%)
Menthol, n (%)0 (0.0%)2 (100.0%)4 (100.0%)2 (50.0%)2 (66.7%)2 (50.0%)3 (100.0%)2 (50.0%)1 (25.0%)0 (0.0%)1 (25.0%)3 (75.0%)2 (50.0%)0 (0.0%)24 (47.1%)
FTCD, Mean (SD)3.3 (2.31)5.5 (2.12)4.8 (1.26)3.0 (2.71)5.0 (3.61)5.0 (1.63)5.3 (0.58)5.3 (1.50)5.0 (2.16)5.0 (1.42)5.0 (1.42)3.8 (1.72)5.5 (2.38)5.5 (1.29)4.8 (1.85)

[i] Abbreviations: BMI = body mass index; CPD = cigarettes per day;FTCD = Fagerström Test for Cigarette Dependence; SD = standarddeviation;

[ii] Products: Product A = eDNC2.0a, Tobacco flavor; Product B = eDNC2.0a, Menthol flavor; Product C = eDNC2.0a, Cherry flavor; Product D = eDNC2.0a, Berry mint flavor; Product E = Usual brand of combustible cigarettes; Product F = Nicotine inhaler; Product G= Reference e-cigarette.

Figure 2.

Mean plasma nicotine concentration profiles in Study 2. Errors bars correspond to standard error.

Table 6.

Summary of the pharmacokinetic parameters for nicotine, Study 2.

Product AProduct BProduct CProduct DProduct EProduct FProduct G
eDNC2.0a Tobacco flavoreDNC2.0a Menthol flavoreDNC2.0a Cherry flavoreDNC2.0a Berry mint flavorUsual brand of combustible cigarettesNicotine inhalerReference e-cigarette
Parameter(n = 51)(n = 51)(n = 51)(n = 50) c(n = 51)(n = 50) c(n = 51 )
Cmax (ng/mL)
Geometric LS mean (95% CI) a4.22 (3.35, 5.31) b4.11 (3.27, 5.18) b3.52 (2.8, 4.44) b3.99 (3.16, 5.03) b12.30 (9.76, 15.49)1.95 (1.55, 2.46)5.74 (4.55, 7.22)
Min, Max0.31, 24.100.36, 17.400.30, 21.600.36, 16.604.38, 34.000.23, 13.000.43, 36.4.0
AUC0–last (ng×hr/mL)
Geometric LS mean (95% CI) a6.71 (5.14, 8.78) b6.62 (5.06, 8.66) b5.28 (4.04, 6.9) b6.17 (4.71, 8.08) b19.02 (14.55, 24.87)3.93 (3, 5.15)7.69 (5.88, 10.05)
Min, Max0.35, 23.170.53, 23.670.15, 17.330.58, 23.333.52, 50.330.02, 31.330.31, 33.33
Tmax (min)
Median10.010.015.010.07.340.07.0
Min, Max5.0, 41.03.0, 61.05.0, 60.05.0, 40.03.0, 40.07.0, 90.03.0, 40.0
Amount of e-liquid used (mg)
Mean (SD)58.2 (33.36)60.7 (34.54)62.4 (35.49)64.8 (39.62)N/AN/A48.2 (29.88)
Min, Max2.0, 171.03.7, 126.92.0, 160.22.2, 203.21.7, 116.8
Estimated nicotine consumption (mg)
Mean (SD)1.05 (0.601)1.09 (0.621)0.93 (0.529)0.96 (0.591)N/AN/A1.45 (0.896)
Min, Max0.04, 3.080.07, 2.280.03, 2.390.03, 3.030.05, 3.50

a Geometric LS means were evaluated separately in a linear mixed-effects analysis of variance (ANOVA) model with fixed effects for period, sequence, product, and a random effect for subject nested within sequence.

b Significantly different from usual brand cigarette; p < 0.05.

c No baseline-adjusted nicotine PK parameters were calculated for a subject because the terminal elimination phase was not well defined when using Product E and F.

Abbreviations: CI = confidential interval; N/A = not applicable; SD = standard deviation; LS = least square.

Table 7.

Summary of the subjective effects measures, Study 2.

ParameterProduct AProduct BProduct CProduct DProduct EProduct FProduct G
eDNC2.0a Tobacco flavoreDNC2.0a Menthol flavoreDNC2.0a Cherry flavoreDNC2.0a Berry mint flavorUsual brand of combustible cigarettesNicotine inhalerReference e-cigarette
(n = 50)(n = 51)(n = 51)(n = 51)(n = 51)(n = 51)(n = 51)
Product liking VAS a
Emax – Mean (SD)41.5 (27.55)51.6 (28.00)51.1 (27.00)52.7 (28.73)77.7 (26.12)29.7 (28.56)58.2 (26.00)
> 50 to 100 mm – n (%)16 (32.0%)27 (52.9%)26 (51.0%)30 (58.8%)45 (88.2%)16 (31.4%)32 (62.7%)
Intent to use the product again VASb
Emax – Mean (SD)44.8 (28.86)53.1 (31.46)54.2 (25.60)55.3 (27.89)83.9 (20.31)24.3 (26.48)59.6 (25.11)
> 50 to 100 mm – n (%)31 (62.0%)34 (66.7%)39 (76.5%)32 (62.7%)48 (94.1%)16 (31.4%)43 (84.3%)
mPES, subscales c
Satisfaction – Mean (SD)2.9 (1.42)3.6 (1.71)3.4 (1.36)3.9 (1.66)5.2 (1.66)1.9 (1.04)3.8 (1.45)
Psychological Reward – Mean (SD)2.7 (1.49)2.7 (1.63)2.7 (1.63)2.9 (1.69)3.6 (1.84)2.1 (1.24)2.9 (1.54)
Aversion – Mean (SD)1.5 (0.89)1.5 (0.64)1.3 (0.65)1.3 (0.54)1.8 (0.94)1.3 (0.66)1.5 (0.72)
Relief – Mean (SD)3.1 (1.75)3.4 (1.84)3.4 (1.71)3.5 (1.91)4.4 (1.96)2.1 (1.45)3.5 (1.70)

a Product liking VAS questionnaire (“Do you like the product effect?”) rating scales with “Not at all (0 mm)” to “Extremely (100 mm)”.

b Intent to Use Product Again VAS questionnaire (“If given the opportunity, would you use this product again?”) rating scales with “Definitely would Not (0 mm)”, “Don’t care (50 mm)”, to “Definitely would (100 mm)”.

c The subscales of modified Product Evaluation Scale (mPES):

  • Satisfaction = average score from 4 questions (“Was it satisfying?”, “Did it taste good?”, “Did you enjoy the sensations in your mouth?” and “Did you enjoy it?”);

  • Psychological reward = average scores from 5 questions (“Did it calm you down?”, “Did it make you feel more awake?”, “Did it make you feel less irritable?”, “Did it help you concentrate?”, and “Did it reduce your hunger for food?”);

  • Aversion = average score from 2 questions (“Did it make you dizzy?” and “Did it make you nauseous?”);

  • Relief = score from a question (“Did it immediately relieve your craving for a cigarette?”). Each item was rated on a 7-point Likert scale ranging from 1 (“Not at all”) to 7 (“Extremely”).

Abbreviations: SD = standard deviation; mPES = modified Product Evaluation Scale; VAS = visual analog square.

Figure 3.

Linear regression of (A) AUC0–last vs. nicotine consumption and (B) Cmax vs. nicotine consumption. Dot lines show the represented fixed effects regression between AUC0–last or Cmax and estimated nicotine consumption derived a linear mixed-model that adjusted the intercepts and slopes by study. R2 indicates the coefficient of determination derived from a simple linear regression (crude regression) taking all data of two studies.

DOI: https://doi.org/10.2478/cttr-2024-0007 | Journal eISSN: 2719-9509 (formerly 1612-9237)
Journal RSS Feed
Language: English, French, German
Page range: 173 - 188
Submitted on: Jan 28, 2024
Accepted on: Apr 24, 2024
Published on: Aug 21, 2024
Published by: Beiträge zur Tabakforschung GmbH
In partnership with: Paradigm Publishing Services
Keywords:
Clinical study,
e-cigarette,
nicotine pharmacokinetics
Related subjects:
Life sciences,
Life sciences, other

© 2024 Dai Yuki, Lesley Giles, Sylvain Larroque, Sam Harbo, Anthony Hemsley, Javier Martinez, published by Beiträge zur Tabakforschung GmbH
This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License.

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