
Figure 1.
Flow chart on identification, exclusion and inclusion of studies considered in this systematic review on WBE studies of tobacco/nicotine product use according to the PRISMA guidelines (136).
Table 1.
Population-normalized consumption of nicotine (PNC, mg/d/1000 persons) based on Cot or Cot + OH-Cot levels in WW reported in 170 data sets from 60 publications.
| All | Europe | America | Asia | Australia/New Zealand | |
|---|---|---|---|---|---|
| N (data sets) | 170 | 107 | 18 | 20 | 25 |
| Mean | 2769 | 2947 | 2543 | 2028 | 2763 |
| SD | 1866 | 1428 | 1112 | 1543 | 3480 |
| Median | 2394 | 2650 | 2673 | 1442 | 1800 |
| 5% Percentile | 807 | 1227 | 189 | 564 | 571 |
| 95% Percentile | 5633 | 5673 | 3940 | 4262 | 8588 |
| Min | 86 | 669 | 162 | 440 | 86 |
| Max | 17000 | 7056 | 4433 | 7034 | 17000 |

Figure 2.
Mean WBE-derived nicotine consumption in 4 continents. Error bars represent the variation between 5% and 95% quantiles.
Table 2.
Studies investigating long-term time trends for WBE-assessed tobacco/nicotine consumption.
| Study | Country | Period (years) | Time trends in nicotine consumption observed | Comparison to sales/surveys | Interpretation by authors |
|---|---|---|---|---|---|
| Mackie et al. 2019 (53) | Australia | 2010–2017 (7 years) |
|
|
|
| Bade et al. 2020 (102) | Australia | 2015–2019 (4 years) |
|
|
|
| Garcia-Lor et al. 2020 (18) | Italy | 2013–2015 (2 years) |
|
|
|
| Zheng et al. 2020 (63) | China | 2012–2017 (5 years) |
|
|
|
| Gao et al. 2020 (31) | China | 2014–2016 (2 years) |
|
|
|
| Boogaerts et al. 2021 (25) | Lithuania | 2018–2019 (1 year) |
|
|
|
| Campo et al. 2023 (137) | Spain | 2018–2020 (2 years)* |
| * Contradictory statements for study period: 2014–2017 in the text |
|
| Thai et al. 2023 (138) | Australia | 2017–2020 (3 years) |
|
|
|
| Wang et al. 2024 (59) | Australia | 2013–2021 (8 years) |
|
|
|
Table 3.
Conditions and assumptions applied in two scenarios of Monte Carlo Simulations (MCSs) for WW concentrations of cotinine (Cot), anabasine (AB) and 2-cyanoethyl mercapturic acid (2CyEMA) of a hypothetical WWTP serving a large city.
| Input variables | Mean value (unit) | Uncertainty | Distribution | Assumptions and Rationale |
|---|---|---|---|---|
| Pop: Catchment population size of the WWTP | 1500000 | 15% | Normal | |
| F: Flow rate of WWTP | 350,000,000 (L/d) | 15% | Normal | |
| UERBM: Daily urinary excretion rates of the BMs | In the rows below, the group- and BM-specific UER values are listed. These are derived from a controlled study with 10 subjects per group (159, 160, 169). As uncertainty, the relative standard errors (RSE) are provided. Specifics are indicated in the last column. Most distributions are between normal and lognormal. As a first approach, normal distributions are assumed. It is assumed that UERs are valid for steady-state conditions. | |||
| UERCotCC | 5.736 (mg/d) | 18% | Normal | |
| UERCotEC | 2.309 (mg/d) | 23% | Normal | UECot values were obtained from reported nicotine equivalents (Nic+10) (160) assuming that Nic+10 represents 95% of the absorbed nicotine dose and that 32.3% are excreted as Cot (free + conjugated) (50) |
| UERCotHTP | 4.240 (mg/d) | 17% | Normal | |
| UERCotONP | 6.625 (mg/d) | 18% | Normal | No values for UERCotONP are available. It is assumed that the UER for ONP users is between those of CC and OT users. |
| UERCotNRT | 2.220 (mg/d) | 31% | Normal | There were mainly nicotine gum users in the controlled study (160) |
| UERCotOT | 7.174 (mg/d) | 19% | Normal | There were mainly snus users in the controlled study (160) |
| UERCotNU | 0.020 (mg/d) | 47% | Normal | |
| UERABCC | 14.6 (µg/d) | 21% | Normal | UERAB values were obtained from the published controlled study (169) |
| UERABEC | 0.50 (µg/d) | 25% | Normal | Outliers were excluded |
| UERABHTP | 2.51 (µg/d) | 22% | Normal | |
| UERABONP | 0.38 (µg/d) | 32% | Normal | No data for ONP were available, the UERAB values for NRT users were applied |
| UERABNRT | 0.38 (µg/d) | 32% | Normal | |
| UERABOT | 22.2 (µg/d) | 50% | Normal | There were mainly snus users in the controlled study (160) |
| UERABNU | 0.21 (mg/d) | 12% | Normal | |
| UER2CyEMACC | 186.4 (µg/d) | 18% | Normal | UER2CyEMA values were obtained from the published controlled study (159) |
| UER2CyEMAEC | 2.52 (µg/d) | 39% | Normal | |
| UER2CyEMAHTP | 14.00 (µg/d) | 28% | Normal | |
| UER2CyEMAONP | 0.58 (µg/d) | 6% | Normal | |
| UER2CyEMANRT | 0.58 (µg/d) | 6% | Normal | Due to obvious outliers, UER2CyEMA values of NU were used |
| UER2CyEMAOT | 0.58 (µg/d) | 6% | Normal | |
| UER2CyEMANU | 0.58 (µg/d) | 6% | Normal | |
| UER for DU (only in Scenario 2) | It is assumed that DUs (simultaneous use of CCs and ECs) exhibit the same daily nicotine uptake as CCs do and would have the same UERCot. For a 20 CPD (cigarettes per day) smoker this could be achieved by reducing the consumption to 10 CPD (= 50% reduction) and simultaneously carry out 25 EC sessions per day. UERABDU and UER2CyEMADU were therefore reduced by 50% compared to the corresponding UER levels for CC-only users. | |||
| Scenario 1: No dual use of CC and EC is assumed | |||
| fCC : Fraction of smokers of CC in the total Pop |
| A constant yearly net decrease of 0.01 is assumed |
|
| fEC : Fraction of vapers (EC) in the total Pop |
| A constant yearly net increase of 0.0036 is assumed |
|
| fHTP : Fraction of HTP users in the total Pop |
| A constant yearly net increase of 0.0018 is assumed |
|
| fONP : Fraction of ONP users in the total Pop |
| A constant yearly net increase of 0.0011 is assumed |
|
| fNRT : Fraction of NRT (any type) users in the total Pop |
| A constant rate of NRT product use over the 10 study years is assumed |
|
| fOT : Fraction of OT (any type) users in the total Pop |
| A constant yearly decrease of 0.00063 is assumed |
|
| fNU : Fraction of non-users (NU) users in the total Pop |
| Fraction of NU arises as a result of subtracting all user groups from the total Pop | |
| Scenario 2: Dual use of CC and EC is assumed | |||
| fCC : Fraction of smokers of CC in the total Pop |
| A constant yearly net decrease of = 0.01 is assumed; from Year 7 to Year 10 an increase of 0.001/year is assumed (back-switchers from DU group) | See Scenario 1 |
| fEC : Fraction of vapers (EC) in the total Pop |
| A constant yearly net increase of 0.004 is assumed; from Year 7 to Year 10 an additional increase of 0.001/year is assumed (DU staying with EC only) |
|
| fHTP : Fraction of HTP users in the total Pop |
| A constant yearly net increase of 0.003 is assumed |
|
| fONP : Fraction of ONP users in the total Pop |
| A constant yearly net increase of 0.002 is assumed |
|
| fNRT : Fraction of NRT (any type) users in the total Pop |
| A constant decrease of 0.0005 of NRT product use over time is assumed |
|
| fOT : Fraction of OT (any type) users in the total Pop |
| A constant yearly decrease of 0.0005 of OT use is assumed |
|
| fDU : Fraction of dual users (DU) of CC and EC in the total Pop |
| A constant yearly increase of 0.001 until Year 7 followed by a net decrease of 0.002 until Year 10 is assumed |
|
| fNU : Fraction of non-users (NU) users in the total Pop |
| Fraction of NU arises as a result of subtracting all user groups from the total Pop | |

Figure 3.
Monte Carlo simulations (MCSs) of Scenario 1 and 2 over 10 years for WW concentrations of cotinine (top), AB (middle) and 2CyEMA (bottom).

Figure 4.
Monte Carlo simulations of Scenario 1 and 2 over 10 years for the WW concentration ratios AB/cotinine (top) and 2CyEMA/cotinine (bottom).