Emissions from Conventional and Electronic Waterpipes Relative to Cigarettes and a Heated Tobacco Product

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Wilkinson, Anna Clarke, Ian M. Fearon, Ronan Barry This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4637991/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Harms associated with tobacco product use, including waterpipe, are due to inhalational exposure to toxicants either present in tobacco or formed during the process of combustion. We assessed levels of 37 toxicants in aerosol emissions from conventional waterpipe heated with different charcoals and also with a heat management device (HMD), from the IQOS heated tobacco product (HTP), and the ‘OOKA’ electronic waterpipe. We also utilised literature data on toxicant yields in 3R4F reference cigarette smoke. When taking use patterns into account, toxicant yields were substantially lower in conventional waterpipe aerosol compared with cigarette smoke. Toxicant yields in electronic waterpipe aerosol were substantially lower than those in conventional waterpipe aerosol, both on a per session basis and when taking typical use patterns into account. Numerous toxicants in conventional waterpipe aerosol were absent in electronic waterpipe aerosol. In summary, during typical use conventional waterpipe emits fewer, and lower levels of, a number of toxicants relative to combustible cigarette smoke. In addition, electronically heating shisha further reduces toxicant levels, and many toxicants are absent in OOKA electronic waterpipe aerosol. These findings have important implications concerning toxicant exposure among waterpipe users, and for understanding how to potentially reduce health risks associated with waterpipe use. Hookah waterpipe shisha electronic waterpipe cigarette heated tobacco product Figures Figure 1 Figure 2 introduction Waterpipe smoking is a form of tobacco use which although global is particularly prevalent in Middle Eastern, Eastern Mediterranean and Eastern European countries 1 – 3 . Waterpipe use involves heating shisha, a mixture which includes tobacco, flavourings, glycerol and sweeteners. The heat source for waterpipe is most commonly wood or coconutderived charcoal briquettes, which are placed on top of the shisha in the bowl or head of the waterpipe, typically separated by a layer of aluminium foil, and lit 4 , 5 . During use, puffing on the mouthpiece of the waterpipe hose draws air over the charcoal and through the shisha, and the resulting aerosol is bubbled through water before being inhaled by the user 4 – 7 . This bubbling potentially removes some of the smoke toxicants, though its primary purpose is to cool the smoke prior to inhalation 4 , 7 . The health risks associated with the use of smoked tobacco products, including waterpipe, arise due to the inhalational exposure of harmful and potentially harmful constituents (HPHCs) and other toxicants 8 , 9 , which may be harmful to the cardiovascular and respiratory systems and may also be carcinogenic 2 , 4 , 5 , 7 , 10 , 11 . These toxicants are either present in the tobacco itself and transferred into the smoke during heating or generated during the processes of pyrolysis and combustion 12 – 14 . However, the largest mass of toxicants present in waterpipe smoke, which include polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene and carbon monoxide (CO), are contributed by the smouldering charcoal 15 , 16 . Other toxicants such as acrolein may be generated upon heating of glycerol and sugars in the shisha tobacco 17 , 18 . Given the association between toxicant generation, exposure, and health risks among tobacco product users, the aim of this study was to assess the levels of HPHCs and other toxicants in aerosols generated from waterpipe heated using different means, including wood and coconutderived charcoal heating, coconutderived charcoal heating in the presence of a heat management device (HMD), and electronic heating. The study addresses a call for more research into emissions from conventionally and electronicallyheated waterpipes 2 and provides muchneeded information concerning the toxicant exposure and the potential for health risks associated with waterpipe use. We additionally assessed toxicant levels in aerosol from the IQOS 3.0 heated tobacco product (HTP), and our findings are placed into context using literature data on 3R4F reference cigarette smoke toxicant levels 19 . RESULTS Study Products Emissions Yields Data concerning absolute yields of the 37 analytes assessed in the machinegenerated emissions from 3R4F reference cigarettes, the IQOS 3.0 HTP used with TEREA Teak sticks, the conventional PM1 shisha smoking machine used with wood and coconutderived charcoal and also with a HMD, and the OOKA electronic waterpipe, are presented in Table 2 . These values are presented as weight per session (waterpipe products) or weight per stick (3R4F reference cigarettes and IQOS 3.0 HTP). Graphical representation of the percentage reductions in analyte yields in electronic waterpipe aerosol compared to yields in the three conventional waterpipe aerosols can be found in Fig. 1 , for those analytes which were detected in conventional waterpipe aerosols. In addition, emissions yields data are presented as weight per puff volume concentrations in Supplementary Table 3. Table 2 Absolute Yields of Emission Analytes from Conventional and Electronic Waterpipe, Reference Cigarettes, and a Heated Tobacco Product. Data are presented as means ± SD from 3 replicates. a Data taken from those reported by Eldridge et al 19 . b Based on 2 replicates. c Average yield when HMD used with 0%, 50% and 100% ventilation settings. Conventional Waterpipe Heated with WoodDerived Charcoal Conventional Waterpipe Heated with CoconutDerived Charcoal Conventional Waterpipe Heated with CoconutDerived Charcoal within a HMD OOKA Electronic Waterpipe IQOS 3.0 (ILUMA) HTP 3R4F Reference Cigarette a Analyte Yield TCM (mg/session) 5224 ± 155 4492 ± 388 3842 ± 509 3257 ± 354 NA NA TPM (mg/stick) NA NA NA NA 33.8 ± 0.6 44.1 ± 2.4 Water (mg/session or stick) 2936.1 ± 123.8 2638.9 ± 215.6 2509.9 ± 315.0 2079.2 ± 142.9 12.89 ± 0.09 15.9 ± 0.7 Nicotine (mg/session or stick) 5.65 ± 0.24 8.70 ± 0.94 5.06 ± 0.98 4.33 ± 0.33 1.08 ± 0.05 1.97 ± 0.04 NFDPM (mg/stick) NA NA NA NA 19.82 ± 0.52 26.3 ± 0.7 Glycerol (mg/session or stick) 1426.7 ± 31.8 1107.9 ± 47.2 750.0 ± 164.1 786.2 ± 31.4 4.73 ± 0.27 ND Propylene Glycol (mg/session or stick) 54.1 ± 3.4 47.7 ± 5.5 39.6 ± 8.9 32.2 ± 2.8 0.0 ± 0.0 ND CO (mg/session or stick) 354.1 ± 22.7 224.2 ± 30.6 71.4 ± 47.6 0.0 ± 0.0 0.20 ± 0.02 31.2 ± 1.0 Benzo[a]pyrene (ng/session or stick) 67.7 ± 27.4 28.9 ± 2.4 7.6 ± 0.2 0.0 ± 0.0 0.0 ± 0.0 13.59 ± 0.69 Formaldehyde (µg/session or stick) 833 ± 126 864 ± 48 589 ± 69 156 ± 30 8 ± 1 72.2 ± 5.8 Acetaldehyde (µg/session or stick) 1275 ± 156 979 ± 72 789 ± 183 303 ± 22 162 ± 23 1235 ± 39 Acetone (µg/session or stick) 477 ± 26 191 ± 152 222 ± 48 9 ± 16 22 ± 4 576 ± 33 Acrolein (µg/session or stick) 368 ± 65 166 ± 108 349 ± 129 14 ± 16 8 ± 1 124.9 ± 8.5 Propionaldehyde (µg/session or stick) 187 ± 27 145 ± 13 63 ± 9 0.0 ± 0.0 10 ± 1 129.7 ± 6.0 Crotonaldehyde (µg/session or stick) 0.0 ± 0.0 0.0 ± 0.0 47 ± 38 0.0 ± 0.0 0.0 ± 0.0 46.4 ± 3.6 2Butanone (µg/per session or stick) 87 ± 20 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 158.7 ± 8.0 Butyraldehyde (µg/session or stick) 108 ± 93 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 21 ± 1.0 86.8 ± 1.1 NNN (ng/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 311.6 ± 20.6 NAT (ng/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 18 ± 1.0 323.0 ± 22.9 NAB (ng/session or stick puffs) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 37.0 ± 3.0 NNK (ng/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 309.6 ± 27.6 1,3Butadiene (µg/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 90.5 ± 25.8 Isoprene (µg/session or stick) 4.9 ± 8.5 7.8 ± 13.5 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 1042.0 ± 76.0 Acrylonitrile (µg/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 33.7 ± 1.5 Benzene (µg/session or stick) 541.0 ± 47.8 256.9 ± 9.8 246.4 ± 62.7 0.0 ± 0.0 0.0 ± 0.0 99.2 ± 5.6 Toluene (µg/session or stick) 174.1 ± 24.8 111.6 ± 46.8 41.2 ± 20.7 0.0 ± 0.0 0.0 ± 0.0 164.0 ± 8.4 1Aminonaphthalene (ng/session or stick) 4.9 ± 5.7 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 22.9 ± 1.5 2Aminonaphthalene (ng/session or stick) 3.4 ± 3.7 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 13.4 ± 0.5 3Aminobiphenyl (ng/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 4.5 ± 0.5 4Aminobiphenyl (ng/session or stick) 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 2.7 ± 0.1 Ammonia (µg/session or stick) 77 ± 16 110.0 ± 25.6 88.3 ± 13.3 0.0 ± 0.0 0.0 ± 0.0 29.8 ± 0.9 Phenol (µg/session or stick) 109.9 ± 3.1 b 98.0 ± 5.9 74.9 ± 17.5 0.0 ± 0.0 0.6 ± 0.1 14.7 ± 0.6 m, pCresol (µg/session or stick) 0.0 ± 0.0 b 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 13.3 ± 0.9 oCresol (µg/session or stick) 0.0 ± 0.0 b 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 4.7 ± 0.2 Catechol (µg/session or stick) 591.6 ± 65.1 b 615.9 ± 21.4 485.6 ± 61.3 161.6 ± 14.9 10.0 ± 0.5 97.7 ± 5.4 Resorcinol (µg/session or stick) 0.0 ± 0.0 b 0.0 ± 0.0 0.0 ± 0.0 3.6 ± 0.5 0.0 ± 0.0 2.3 ± 0.4 Hydroquinone (µg/session or stick) 402.6 ± 55.7 b 278.2 ± 21.4 374.9 ± 46.4 115.2 ± 13.0 8.7 ± 0.3 86.7 ± 4.9 Abbreviations: SD, standard deviation; HTP, heated tobacco product; HMD, heat management device; TCM, total collected matter; TPM, total particulate matter; NFDPM, nicotinefree dry particulate matter; CO, carbon monoxide; NNN, N ’nitrosonornicotine; NAT, N ’nitrosoanatabine; NAB, N nitrosoanabasine ; NNK, 4(methylnitrosamino)-1(3pyridyl)-1butanone; NA, not applicable; ND, not determined. Compared with cigarette smoke and HTP aerosol, some analytes were present in aerosol from the conventional waterpipe variants at higher levels when examined on a per stick/per session basis. For CO and glycerol, these arise due to the method of heating and the level of the humectant in the shisha tobacco, respectively. Of note, waterpipe aerosol CO yields were lower when using coconutderived, as opposed to woodderived charcoal as a heating source, and were lowered even further by the use of a HMD. Furthermore, CO was completely absent in aerosol generated from the electronic waterpipe due to it operating at temperatures lower than those which support combustion, and present at extremely low levels in HTP aerosol. The tobaccospecific nitrosamines (TSNAs) NNN, NNK, NAT and NAB were detected in 3R4F reference cigarette smoke at high levels but were not detected in the aerosol from either the conventional waterpipe variants or the electronic waterpipe. Of the TSNAs, only NAT was detected, at low levels, in IQOS 3.0 aerosol. Of the aldehydes assessed, formaldehyde was detected in aerosol from the conventional waterpipe variants at levels greater than those in 3R4F reference cigarette smoke. While this was also the case for the electronic waterpipe, formaldehyde levels in the electronic waterpipe aerosol were approximately 74–82% lower than those in conventional waterpipe aerosol. Formaldehyde was detected in HTP aerosol at levels approximately 90% lower than those in 3R4F reference cigarette smoke. Acetaldehyde was detected in conventional waterpipe aerosol at levels similar to, or lower than, those in 3R4F reference cigarette smoke depending on the charcoal used or the presence of the HMD. Acetaldehyde levels in electronic waterpipe aerosol were approximately 75% lower than those in cigarette smoke, and between approximately 61% and 76% lower than the levels in conventional waterpipe aerosol. Acrolein was detected at levels in conventional waterpipe aerosol at levels higher than those in 3R4F reference cigarette smoke, and the levels were dependent on the type of charcoal used. This analyte was detected in electronic waterpipe aerosol at levels approximately 89% lower than in cigarette smoke and between approximately 91% and 96% lower than levels in conventional waterpipe aerosol. Other aldehydes including propionaldehyde, crotonaldehyde and butyraldehyde were present in aerosols from some of the conventional waterpipe variants assessed, and at levels of the same magnitude as those in 3R4F reference cigarette smoke but were absent in aerosol from the electronic waterpipe. Other analytes detected in conventional waterpipe aerosols at levels comparable to or higher than those in 3R4F reference cigarette smoke include benzene, toluene and ammonia, three analytes which were absent in electronic waterpipe and HTP aerosols. Phenol was present in the conventional waterpipe aerosols at levels higher than those in 3R4F reference cigarette smoke but was absent in the electronic waterpipe aerosol. Some analytes, including 1,3butadiene, isoprene, acrylonitrile, and cresols, were detected in cigarette smoke but were absent in the aerosols of all other products tested. Estimated Weekly Emissions Yields Based on assumed weekly consumption of 2 waterpipe sessions per week and 20 cigarettes per day as stated by the German Federal Institute for Risk Assessment 20 , absolute emissions yields on a per session (conventional and electronic waterpipe) or a per stick (IQOS 3.0 and 3R4F reference cigarettes) basis were used to calculate estimated weekly emissions yields. Data arising from this analysis are presented for nicotine and the nine analytes mandated for lowering in cigarette smoke in the World Health Organization (WHO) Study Group on Tobacco Product Regulation (TobReg) proposal 21 in Fig. 2 , expressed as percentage estimated weekly yields from conventional and electronic waterpipes relative to yields from 3R4F reference cigarettes. Weekly estimated nicotine yields from the conventional waterpipe variants, and also from the electronic waterpipe, were vastly lower than those from both the reference cigarette and the HTP. Of the TobReg analytes, NNN, NNK and 1,3butadiene were absent in conventional and electronic waterpipe emissions and HTP aerosol and their estimated weekly yields were therefore zero. Of the aldehydes, weekly estimated acrolein yields from the conventional waterpipe variants were estimated at between 4.1% and 1.9%, and for the electronic waterpipe 0.2%, of the reference cigarette yield. Weekly acetaldehyde yields were approximately 1% of reference cigarette yields for the conventional waterpipe variants, 0.35% for the electronic waterpipe, and approximately 13% for the HTP. Formaldehyde yields ranged between approximately 10% and 17% of reference cigarette yields for the HTP and the conventional waterpipe variants, and approximately 3% for the electronic waterpipe. For other TobReg analytes, benzene and benzo[a]pyrene estimated weekly yields were zero for both the electronic waterpipe and the HTP and for the conventional waterpipe variants ranged from 7.8–0.8% of reference cigarette estimated weekly yields. Finally, relative to the reference cigarette weekly estimated yield, the CO yield was approximately 0.6% for the HTP, and zero for the electronic waterpipe due to the absence of this analyte in electronic waterpipe aerosol. The weekly estimated CO yield for the conventional waterpipe variants ranged from approximately 3–16% of the reference cigarette yield. DISCUSSION In this study assessing aerosol yields from conventional and electronic waterpipes, a HTP, and a reference cigarette, our findings suggest that conventional waterpipe may expose users to lower levels of HPHCs and other harmful toxicants than combusted tobacco cigarettes. For a number of analytes, including the TobReg analytes CO, benzo[a]pyrene, formaldehyde, acetaldehyde, benzene and acrolein, we also demonstrate that the potential for exposure during conventional waterpipe use can be reduced either by using different types of charcoal or by placing the charcoal in a HMD on top of the shisha head before the charcoal is lit. However, while the use of different charcoals and/or a HMD may reduce the infiltration of toxicants such as CO into the conventional waterpipe aerosol, they are still present in substantial amounts. Heating the shisha tobacco by electronic means further reduces the levels of, or removes, these toxicants. In the case of CO, benzo[a]pyrene, propionaldehyde, crotonaldehyde, 2butanone, butyraldehyde, benzene, toluene and phenol, all were absent in the electronic waterpipe aerosol. Overall, our findings suggest that conventional waterpipe is a relatively low exposure and potentially low toxicity heated tobacco product, in which the aerosol is contaminated by toxicants arising from combustion of the charcoal or charring of the shisha tobacco. This contamination can be mitigated and/or eliminated by various means such as using different charcoal or a HMD, or by heating the shisha tobacco by electronic means at temperatures lower than those which support combustion. Our findings generally concur with those in the extant literature, including chemistry assessments which have reported lower levels of acrolein and crotonaldehyde in charcoalheated shisha compared with cigarette smoke, and the absence of NNK, NNN and benzo[a]pyrene, in waterpipe aerosol 22 . Our findings also concur with clinical studies which have reported lower exposure to HPHCs and other toxicants among waterpipe users compared with cigarette smokers 11 , 23 – 26 . Regarding our findings for the electronic waterpipe, Hourani et al 15 reported substantial reductions in levels of PAHs (80% reduction) and CO (90% reduction) in aerosols generated from waterpipes which used electrical heating elements compared with aerosol levels from waterpipe which used conventional charcoal heating. In our study, PAHs including benzo[a]pyrene, 1aminonapthalene and 2aminonapthelene, and CO, were detected in conventional waterpipe aerosol but were absent in electronic waterpipe aerosol. In contrast to the previous study however, Hourani et al 15 reported that the levels of volatile aldehydes such as acrolein were severalfold higher in the waterpipe heated using an electrical heating element compared with conventional charcoalheated waterpipe. In our study, aerosol aldehyde yields of formaldehyde, acetaldehyde, acrolein, propionaldehyde, crotonaldehyde and butyraldehyde were substantially lower in electronic waterpipe aerosol, with those reductions, depending on the conventional waterpipe assessed, ranging from approximately 62% for acetaldehyde to 100% for propionaldehyde, crotonaldehyde and butyraldehyde. For formaldehyde and acrolein, percentage reductions were between approximately 74% and 82% and between approximately 91% and 96%, respectively, depending on the conventional waterpipe heating method. The reasons for these differences are unclear. One potential reason is that the electronic waterpipe used in our study uses precise temperature control which the aftermarket electrical heating elements for conventional waterpipe used by Hourani et al 15 may not provide. Such uncontrolled heating may increase the levels of aldehydes, which can be formed as thermal breakdown products of the humectants propylene glycol and glycerol 18 , 27 which are used as additives in shisha tobacco 28 , 29 . It is important, when undertaking both absolute and relative human health risk assessments of tobacco and nicotine products, and to understand any risks associated with realworld use, to take use patterns such as quantity and frequency of use into account 30 . In this paper, we utilised our aerosol yield data and integrated this with estimated average consumption patterns (2 waterpipe sessions per week and 20 cigarettes per day 20 ) to generate an overall assessment of the potential for exposure to nicotine and the nine analytes mandated for lowering in cigarette smoke in the WHO TobReg proposal 21 . Using this approach, we demonstrated that overall exposure associated with the use of conventional waterpipe, electronic waterpipe, and the IQOS HTP, was either substantially reduced or eliminated for the analytes assessed. This has the potential to mitigate the health risks associated with tobacco product use, although due to the nonlinearity of the exposureresponse the degree of risk mitigation cannot be estimated 31 – 34 . These exposure mitigations are however likely to have implications for both individual and population health. For example, in vitro and animal studies have demonstrated a reduced toxicological and pathological impact of waterpipe aerosol compared with cigarette smoke 22 , 35 , 36 . In human clinical studies, the reduced exposure profile of the IQOS HTP has been shown to result, at least in the short to mediumterm, in beneficial changes in indicators of disease risk 37 – 39 , though similar studies have not been conducted for waterpipes. Importantly, our emissions analysis, as well as data in the literature, may serve to correct certain misperceptions regarding waterpipe use 40 . Firstly, it has been reported that waterpipe tobacco has a significantly higher nicotine content than cigarettes, with one head of shisha tobacco reportedly containing the nicotine equivalent of 70 cigarettes 41 . In this paper, while we report that the nicotine concentration in the aerosol from both conventional and electronic waterpipe was approximately 2 to 4times higher than that in 3R4F reference cigarette smoke when assessed on a per session or per stick basis. However, it has to be considered that waterpipe use sessions last much longer than cigarette smoking sessions and include substantially more puffs 40 . When these factors are taken into account, aerosol nicotine content on an amount per puff volume or on a per puff basis are substantially lower for conventional waterpipe compared with cigarettes, and even lower for the OOKA electronic waterpipe assessed in the study. This is supported by previous findings that waterpipe use was associated with significantly lower intake of nicotine 11 , 23 , 25 , 26 and this is also associated with significantly lower exposure to NNK, naphthalene, fluorene, acrylonitrile, acrolein, 1–3,butadiene and other toxicants among waterpipe users compared with cigarette smokers 11 , 23 – 25 . It has also been asserted that smoke exposure from a single waterpipe session could be as much as that from 100–200 cigarettes 42 – 44 . This contrasts with the findings of this study, in which the greatest difference between the levels of a toxicant, formaldehyde, in conventional waterpipe aerosol compared with cigarette smoke on an amount per puff volume or on a per puff basis was a 10fold difference. Furthermore, this does not take into account typical use patterns to arrive at a human health risk estimate, as undertaken in this study, based on realworld emissions yields and potential for exposure. When taking use patterns into account, out data suggest that the potential for overall exposure to HPHCs and other toxicants associated with waterpipe use are likely to be substantially lower than potential exposure due to cigarette smoking. Our study and its findings are subject to some limitations. Firstly, for the conventional waterpipe we assessed emissions using a standardised shisha smoking machine, two different types of charcoal, a HMD, and a single type of shisha tobacco. Our findings may not be generalisable to the many different types of conventional waterpipes, charcoals, HMDs, and shisha tobaccos, that are available to consumers. In addition, the OOKA electronic waterpipe assessed in this study, which heats a shisha tobacco blend very similar in composition to the shisha tobacco used for conventional waterpipe aerosol generation, is a very different device than ‘eshisha’ or ‘ehookah’ devices. The majority of ehookah devices operate in a manner not dissimilar to electronic cigarettes 5 , 45 and use a metallic coil to vaporise an eliquid solution which is flavoured to mimic the taste of shisha 5 . Given the marked dissimilarity between the electronic waterpipe assessed in this study and ‘ehookah’, our findings cannot be extrapolated to ehookah devices. Secondly, our study used a standardised puffing regimen to generate aerosols for all the products assessed. Realworld use patterns, in which users puff on the waterpipe differently to the puffing regimen prescribed by the ISO regimen used in this study, may give rise to different aerosol toxicant yields, as has been reported both for waterpipe 46 – 48 and other tobacco/nicotine products 49 . Thirdly, our reported relative differences in machinederived aerosol toxicant yields may not be indicative of actual relative exposure, and human clinical studies assessing biomarkers of exposure are required in order to assess relative exposure from different types of tobacco products and different waterpipe heating methods. That said, our finding that a number of HPHCs and other toxicants are absent in machinederived conventional and electronic waterpipe aerosols can be assumed to lead to an absence of exposure. Fourthly, we only measured 37 analytes in the tobacco product aerosols, and our findings are therefore limited to potential exposure to those chemicals. In summary, conventional waterpipe aerosol contains fewer, and lower levels of, a number of HPHCs and other toxicants relative to combustible cigarette smoke, both when assessed as analyte levels and also when taking into account typical use patterns. The levels of toxicants can be reduced either by using different types of charcoal or by using a HMD. In addition, heating the shisha tobacco by electronic means in the OOKA waterpipe drives toxicant levels down even further, and many of these toxicants, such as CO, acetaldehyde, acrolein, benzene and benzo[a]pyrene, are absent from the OOKA electronic waterpipe aerosol. These findings have important implications for understanding toxicant yields and potential exposure among waterpipe users, and for understanding how to potentially reduce the health risks associated with waterpipe use. Furthermore, similar to the manner in which innovation in electronic tobacco heating in HTPs may reduce the health risks associated with cigarette smoking, applying similar principles to waterpipe use, and using innovative non-combusting heating methods, can potentially reduce harms associated with waterpipe use. METHODS Study Products Images of the products assessed in this study can be found in Supplementary Table 1. Conventional waterpipe emissions were generated using a PM1 shisha smoking machine (Körber Technologies Instruments, Hamburg, Germany), a smoking machine specifically designed for the smoking of shisha tobacco. The shisha tobacco used was “Two Apples” (Al Fakher, Dubai, UAE). The charcoals used were Quick Light beech woodderived charcoal (Three Kings, Bladel, Netherlands) and BLACKCOCO’s CUBES26 coconutderived charcoal (BLACKCOCO’s GmbH, Heilbronn, Germany). The HMD used was a Lotus device (Kaloud, CA, US), which is comprised of an aluminium vessel in which the charcoal is placed. This vessel is then housed on the head of the waterpipe, approximately 3 mm above the shisha tobacco and controls the transfer of heat to the tobacco. The combustible cigarette was a Kentucky 3R4F reference cigarette (University of Kentucky, KY, US). The HTP used was an IQOS 3.0 device (“ILUMA”; Philip Morris International (PMI), Lausanne, Switzerland), used with TEREA “Teak” tobacco sticks (PMI) which are specifically designed for use with the IQOS 3.0 inductive heating HTP. The electronic waterpipe used was an OOKA waterpipe with “Two Apples” OOKA pods (Advanced Inhalation Rituals, Dubai, UAE), which were selected since they contain a shisha tobacco blend very similar in composition to the shisha tobacco used for conventional waterpipe aerosol generation. Unlike conventional shisha, which uses heat convection through the air stream and heat radiation from the bottom of the foil, OOKA uses heat conduction to heat the shisha molasses. OOKA has a thin-film heating element on the wall of a micro-oven which conducts heat into the OOKA pod. Sensors placed around the micro-oven allow the temperature to be accurately measured allowing the OOKA to rapidly modify the heat energy inside the pod to reduce accidental overheating associated with conventional charcoalheated waterpipes. PM1 Shisha Smoking Machine Preparation A 10 g sample of shisha tobacco was placed into the head of the PM1 shisha smoking machine. The head was covered in aluminium foil and a puncher used to create uniform perforations. Either wood or coconutderived charcoal was placed centrally on the foil and lit using a gas lighter. The waterpipe head was connected to the bottle containing 750 ml deionized water, as per International Organisation for Standardisation (ISO) Technical Specification 22486 “Water pipe tobacco smoking machine - Definitions and standard conditions” 50 . The waterpipe head was protected from ambient air currents using a glass screen, a setup which is representative of typical use by consumers. When the PM1 shisha smoking machine was used with the Lotus HMD, the same amount of shisha tobacco was placed into the shisha head, the charcoal was placed into the HMD and lit, and the HMD was placed on top of the shisha tobacco. The Lotus HMD can be set to allow different ventilation levels, and levels of 100%, 50% and 0% were used in this study. Data are presented in this paper as average yields obtained when using these three different ventilation levels. Waterpipe Aerosol and Cigarette Smoke Collection & Analysis Puffing parameters used for waterpipe aerosol/cigarette smoke generation are shown in Table 1 . Conventional and electronic waterpipe aerosols generated using the PM1 shisha smoking machine and the OOKA electronic waterpipe were collected in a onehour session according to ISO 22486. Aerosol from the IQOS 3.0 HTP was generated using the Health Canada Intense (HCI) machine smoking regimen 51 . Aerosols from both conventional and electronic waterpipes, and the IQOS 3.0 HTP, were generated and analysed at ASL Analytic Service Laboratory GmbH (Hamburg, Germany), an ISO 17025 accredited laboratory. Mainstream smoke yields from 3R4F reference cigarettes were taken from a published study which generated cigarette smoke using the HCI machine smoking regimen, also at an ISO 17025 accredited laboratory 19 . Analytical Methods Details of the analytical methods used to measure emissions analytes can be found in Supplementary Table 2. Data Analyses Emissions generation and analytical chemistry assessments were performed in triplicate, unless otherwise stated. Data are presented using descriptive statistics (means ± standard deviations (SD) from the three replicates). Concentrations of analytes in the emissions from the products assessed are also presented; these data were calculated from the absolute yields using total puff volumes of 92.75 l for the conventional and electronic waterpipe products (175 puffs of 530 ml volume), 0.55 l for IQOS 3.0 (11 puffs of 55 ml volume), and 0.572 0.605 l for the 3R4F reference cigarette (based on an average number of 55 ml volume puffs, depending on the analyte, reported in Eldridge et al 19 ). We also further present data as estimated percentage weekly emissions yields from the conventional and electronic waterpipe and the IQOS 3.0 HTP relative to estimated weekly yields from conventional cigarettes. These were derived using assumed weekly consumption of 2 waterpipe sessions per week and 20 cigarettes per day, as stated by the German Federal Institute for Risk Assessment 20 . Declarations Acknowledgements The authors gratefully acknowledge the support of ASL Analytical Services Laboratory GmBH (Hamburg, Germany) in conducting the emissions generation and chemical analyses. Author contributions PJW, AC and RB designed the study. IMF assessed and contextualized the data and wrote the initial draft manuscript. All authors contributed to editing and approving the final manuscript. Data availability statement The datasets generated during the study are available from the corresponding author on reasonable request. Competing interests This study was funded by Advanced Inhalation Rituals Ltd, a manufacturer of conventional shisha tobacco products and of the OOKA electronic waterpipe and associated shisha tobacco pods. PJW, AC and RB are employees of Advanced Inhalation Rituals Ltd. IMF is a Non‑Executive Director with Advanced Inhalation Rituals Ltd, an independent consultant to tobacco and nicotine product manufacturers and contract research organisations, and a retained Scientific Advisory Board member of Qnovia, LLC. IMF holds shares in British American Tobacco and Qnovia, LLC. Funding This study was funded by Advanced Inhalation Rituals Ltd. References Almomen, S. et al. Effect of glycerol concentration on levels of toxicants emissions from water-pipe tobacco smoking (WTS). BMC Public Health 23 , 1858, doi:10.1186/s12889-023-16740-2 (2023). Kienhuis, A. S. & Talhout, R. Options for waterpipe product regulation: A systematic review on product characteristics that affect attractiveness, addictiveness and toxicity of waterpipe use. Tob Induc Dis 18 , 69, doi:10.18332/tid/125079 (2020). Tee, G. H. et al. Systematic review on international practices in controlling waterpipe tobacco smoking. Asian Pac J Cancer Prev 16 , 3659-3665, doi:10.7314/apjcp.2015.16.9.3659 (2015). Jukema, J. B., Bagnasco, D. E. & Jukema, R. A. Waterpipe smoking: not necessarily less hazardous than cigarette smoking : Possible consequences for (cardiovascular) disease. Neth Heart J 22 , 91-99, doi:10.1007/s12471-013-0501-0 (2014). Bhatnagar, A. et al. Water Pipe (Hookah) Smoking and Cardiovascular Disease Risk: A Scientific Statement From the American Heart Association. Circulation 139 , e917-e936, doi:10.1161/cir.0000000000000671 (2019). Erythropel, H. C. et al. Quantification of Flavorants and Nicotine in Waterpipe Tobacco and Mainstream Smoke and Comparison to E-cigarette Aerosol. Nicotine Tob Res 23 , 600-604, doi:10.1093/ntr/ntaa114 (2021). Yadav, S. Decoding Waterpipe Tobacco Smoking: A Comprehensive Narrative Review Exploring Mechanics, Health Risks, Regulatory Challenges, and Public Health Imperatives. Cureus 16 , e52168, doi:10.7759/cureus.52168 (2024). Food and Drug Administration. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List. Docket No. FDA–2012–N–0143. Federal Register 77 (2012). Primack, B. A. et al. Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking. Public Health Rep 131 , 76-85, doi:10.1177/003335491613100114 (2016). Darawshy, F., Abu Rmeileh, A., Kuint, R. & Berkman, N. Waterpipe smoking: a review of pulmonary and health effects. Eur Respir Rev 30 , doi:10.1183/16000617.0374-2020 (2021). Etemadi, A. et al. Urinary Biomarkers of Carcinogenic Exposure among Cigarette, Waterpipe, and Smokeless Tobacco Users and Never Users of Tobacco in the Golestan Cohort Study. Cancer Epidemiol Biomarkers Prev 28 , 337-347, doi:10.1158/1055-9965.Epi-18-0743 (2019). Baker, R. R. Smoke generation inside a burning cigarette: Modifying combustion to develop cigarettes that may be less hazardous to health. Progress in Energy and Combustion Science 32 , 373-385, doi:https://doi.org/10.1016/j.pecs.2006.01.001 (2006). Hertz-Schünemann, R. et al. High-resolution time and spatial imaging of tobacco and its pyrolysis products during a cigarette puff by microprobe sampling photoionisation mass spectrometry. Anal Bioanal Chem 407 , 2293-2299, doi:10.1007/s00216-014-8447-7 (2015). White, J. L. et al. Effect of pyrolysis temperature on the mutagenicity of tobacco smoke condensate. Food Chem Toxicol 39 , 499-505, doi:10.1016/s0278-6915(00)00155-1 (2001). El Hourani, M. et al. Comparison of CO, PAH, Nicotine, and Aldehyde Emissions in Waterpipe Tobacco Smoke Generated Using Electrical and Charcoal Heating Methods. Chem Res Toxicol 32 , 1235-1240, doi:10.1021/acs.chemrestox.9b00045 (2019). Monzer, B., Sepetdjian, E., Saliba, N. & Shihadeh, A. Charcoal emissions as a source of CO and carcinogenic PAH in mainstream narghile waterpipe smoke. Food Chem Toxicol 46 , 2991-2995, doi:10.1016/j.fct.2008.05.031 (2008). Stevens, J. F. & Maier, C. S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res 52 , 7-25, doi:10.1002/mnfr.200700412 (2008). Landmesser, A. et al. Assessment of the potential vaping-related exposure to carbonyls and epoxides using stable isotope-labeled precursors in the e-liquid. Arch Toxicol 95 , 2667-2676, doi:10.1007/s00204-021-03097-x (2021). Eldridge, A., Betson, T. R., Gama, M. V. & McAdam, K. Variation in tobacco and mainstream smoke toxicant yields from selected commercial cigarette products. Regul Toxicol Pharmacol 71 , 409-427, doi:10.1016/j.yrtph.2015.01.006 (2015). Deutsche Bundesinstitut fur Riskobewertung. Frequently asked questions about waterpipes , (2018). Burns, D. M. et al. Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal. Tob Control 17 , 132-141, doi:10.1136/tc.2007.024158 (2008). Tellez, C. S. et al. Comparative Genotoxicity and Mutagenicity of Cigarette, Cigarillo, and Shisha Tobacco Products in Epithelial and Cardiac Cells. Toxicol Sci 184 , 67-82, doi:10.1093/toxsci/kfab101 (2021). Jacob, P., 3rd et al. Comparison of nicotine and carcinogen exposure with water pipe and cigarette smoking. Cancer Epidemiol Biomarkers Prev 22 , 765-772, doi:10.1158/1055-9965.Epi-12-1422 (2013). Radwan, G., Hecht, S. S., Carmella, S. G. & Loffredo, C. A. Tobacco-specific nitrosamine exposures in smokers and nonsmokers exposed to cigarette or waterpipe tobacco smoke. Nicotine Tob Res 15 , 130-138, doi:10.1093/ntr/nts099 (2013). Kaplan, B. et al. Waterpipe tobacco smoke: Characterization of toxicants and exposure biomarkers in a cross-sectional study of waterpipe employees. Environ Int 127 , 495-502, doi:10.1016/j.envint.2019.03.074 (2019). Primack, B. A. et al. Comparison of toxicant load from waterpipe and cigarette tobacco smoking among young adults in the USA. Tob Control , doi:10.1136/tobaccocontrol-2017-054226 (2018). Gillman, I. G., Pennington, A. S. C., Humphries, K. E. & Oldham, M. J. Determining the impact of flavored e-liquids on aldehyde production during Vaping. Regulatory Toxicology and Pharmacology 112 , 104588, doi:https://doi.org/10.1016/j.yrtph.2020.104588 (2020). Uebelacker, L. et al. [In vitro exposure of the shisha tobacco ingredient glycerol to human mucosa cells and lymphocytes]. Laryngorhinootologie 98 , 398-407, doi:10.1055/a-0885-1826 (2019). Jaccard, G., Tafin Djoko, D., Korneliou, A. & Belushkin, M. Analysis of waterpipe aerosol constituents in accordance with the ISO standard 22486. Toxicol Rep 7 , 1344-1349, doi:10.1016/j.toxrep.2020.10.007 (2020). Staal, Y. C. M., Bos, P. M. J. & Talhout, R. Methodological Approaches for Risk Assessment of Tobacco and Related Products. Toxics 10 , doi:10.3390/toxics10090491 (2022). Cox, L. A., Jr. Low-dose nonlinear effects of smoking on coronary heart disease risk. Dose Response 10 , 219-232, doi:10.2203/dose-response.11-038.Cox (2012). Zou, L. et al. Non-linear dose–response relationship between cigarette smoking and pancreatic cancer risk: Evidence from a meta-analysis of 42 observational studies. European Journal of Cancer 50 , 193-203, doi:https://doi.org/10.1016/j.ejca.2013.08.014 (2014). Cox, L. A. Implications of nonlinearity, confounding, and interactions for estimating exposure concentration-response functions in quantitative risk analysis. Environmental Research 187 , 109638, doi:https://doi.org/10.1016/j.envres.2020.109638 (2020). Smith, C. J., Fischer, T. H. & Sears, S. B. Environmental Tobacco Smoke, Cardiovascular Disease, and the Nonlinear Dose-Response Hypothesis. Toxicological Sciences 54 , 462-472, doi:10.1093/toxsci/54.2.462 (2000). Ghosh, B. et al. Effect of sub-chronic exposure to cigarette smoke, electronic cigarette and waterpipe on human lung epithelial barrier function. BMC Pulm Med 20 , 216, doi:10.1186/s12890-020-01255-y (2020). Mayyas, F. et al. Comparison of the cardiac effects of electronic cigarette aerosol exposure with waterpipe and combustible cigarette smoke exposure in rats. Life Sci 251 , 117644, doi:10.1016/j.lfs.2020.117644 (2020). Haziza, C. et al. Favorable Changes in Biomarkers of Potential Harm to Reduce the Adverse Health Effects of Smoking in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 2). Nicotine Tob Res 22 , 549-559, doi:10.1093/ntr/ntz084 (2020). Lüdicke, F. et al. Effects of Switching to a Heat-Not-Burn Tobacco Product on Biologically Relevant Biomarkers to Assess a Candidate Modified Risk Tobacco Product: A Randomized Trial. Cancer Epidemiol Biomarkers Prev 28 , 1934-1943, doi:10.1158/1055-9965.Epi-18-0915 (2019). Lüdicke, F. et al. Effects of Switching to the Menthol Tobacco Heating System 2.2, Smoking Abstinence, or Continued Cigarette Smoking on Clinically Relevant Risk Markers: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 2). Nicotine Tob Res 20 , 173-182, doi:10.1093/ntr/ntx028 (2018). Chaouachi, K. A critique of the WHO TobReg's "Advisory Note" report entitled: "Waterpipe tobacco smoking: health effects, research needs and recommended actions by regulators". J Negat Results Biomed 5 , 17, doi:10.1186/1477-5751-5-17 (2006). World Health Organization. Tobacco Free Initiative. The truth about waterpipe use , (2024). Yadav, S. & Rawal, G. Waterpipe Tobacco Smoking: A Mini-review. J Transl Int Med 6 , 173-175, doi:10.1515/jtim-2016-0013 (2018). World Health Organization. Tobacco use in Shisha. Studies on waterpipe smoking in Egypt , (2006). Centers for Disease Control and Prevention. Hookahs , (2021). Kotecha, S., Jawad, M. & Iliffe, S. Knowledge, attitudes and beliefs towards waterpipe tobacco smoking and electronic shisha (e-shisha) among young adults in London: a qualitative analysis. Prim Health Care Res Dev 17 , 166-174, doi:10.1017/s1463423615000237 (2016). Eddingsaas, N. C. et al. Effect of user puffing topography on total particulate matter, nicotine and volatile carbonyl emissions from narghile waterpipes. Tob Control 29 , s117-s122, doi:10.1136/tobaccocontrol-2019-054966 (2020). Cobb, C. O. et al. Comparison of puff topography, toxicant exposure, and subjective effects in low- and high-frequency waterpipe users: a double-blind, placebo-control study. Nicotine Tob Res 17 , 667-674, doi:10.1093/ntr/ntu196 (2015). Maziak, W. et al. Nicotine exposure in daily waterpipe smokers and its relation to puff topography. Addict Behav 36 , 397-399, doi:10.1016/j.addbeh.2010.11.013 (2011). Wadkin, R., Allen, C. & Fearon, I. M. E-cigarette puffing topography: The importance of assessing user behaviour to inform emissions testing. Drug Test Anal 15 , 1222-1232, doi:10.1002/dta.3322 (2023). International Organization for Standardization. (2019). Government of Canada. Tobacco reporting regulations. SOR/2000-273 , (2000). Additional Declarations Competing interest reported. This study was funded by Advanced Inhalation Rituals Ltd, a manufacturer of conventional shisha tobacco products and of the OOKA electronic waterpipe and associated shisha tobacco pods. PJW, AC and RB are employees of Advanced Inhalation Rituals Ltd. IMF is a Non Executive Director with Advanced Inhalation Rituals Ltd, an independent consultant to tobacco and nicotine product manufacturers and contract research organisations, and a retained Scientific Advisory Board member of Qnovia, LLC. IMF holds shares in British American Tobacco and Qnovia, LLC. Supplementary Files SupplementaryMaterials.pdf Cite Share Download PDF Status: Published Journal Publication published 30 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Oct, 2024 Reviews received at journal 31 Aug, 2024 Reviewers agreed at journal 21 Aug, 2024 Reviews received at journal 28 Jul, 2024 Reviewers agreed at journal 10 Jul, 2024 Reviewers invited by journal 05 Jul, 2024 Editor assigned by journal 05 Jul, 2024 Editor invited by journal 01 Jul, 2024 Submission checks completed at journal 01 Jul, 2024 First submitted to journal 25 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4637991","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":329491642,"identity":"10e20735-d2b3-42fb-bfe3-1fed30ae22f0","order_by":0,"name":"Peter J. Wilkinson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYJCCAw8OSIBoxgcMBkCKnYGNgaGAgJYEiBZmA7AWZpAWAwLWJBwAU2xgjQS1mDPwGB5IOGORJ9/ee6ziR8E9Bnln5mMPfuDRYtnAY3Ag4YZEscGZc2k3ewyKGQwPs6Ub9uDRYnCAd8OBhA8SiRskcsxu8BgkMBg285hJ8BCjZf6MHLPCP1Atkn8IarkhkdhwI8eMGWSLPDOPmTQ+Wyyb+T8AvQ902JkzxtIyBgk8Bsxs6cYy+EKMvS35w4djdYnz23sMP775kyAn39587OGbCjwOY0YTAAYgbtUQLRgi8g0EtIyCUTAKRsGIAwAs+E+8raBOagAAAABJRU5ErkJggg==","orcid":"","institution":"Advanced Inhalation Rituals Ltd, Festival Office Tower","correspondingAuthor":true,"prefix":"","firstName":"Peter","middleName":"J.","lastName":"Wilkinson","suffix":""},{"id":329491644,"identity":"d78c228a-1ed3-4388-b6c6-a16e8f4dd8c4","order_by":1,"name":"Anna Clarke","email":"","orcid":"","institution":"Advanced Inhalation Rituals Ltd, Festival Office Tower","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Clarke","suffix":""},{"id":329491646,"identity":"eb0a399b-73e5-482a-b87e-5d460bc3ac1d","order_by":2,"name":"Ian M. Fearon","email":"","orcid":"","institution":"whatIF? Consulting Ltd","correspondingAuthor":false,"prefix":"","firstName":"Ian","middleName":"M.","lastName":"Fearon","suffix":""},{"id":329491648,"identity":"1b9f8415-1ddb-473e-acb4-acd1b8ba59a9","order_by":3,"name":"Ronan Barry","email":"","orcid":"","institution":"Advanced Inhalation Rituals Ltd, Festival Office Tower","correspondingAuthor":false,"prefix":"","firstName":"Ronan","middleName":"","lastName":"Barry","suffix":""}],"badges":[],"createdAt":"2024-06-25 17:00:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4637991/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4637991/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-90721-w","type":"published","date":"2025-04-30T15:57:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60896272,"identity":"0833b3fe-ae65-4d6f-9cc7-7f50ced4c76a","added_by":"auto","created_at":"2024-07-23 09:56:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":143075,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReductions in Aerosol Yields from the Electronic Waterpipe Compared to Yields from the Conventional Waterpipe Variants.\u003c/strong\u003e Data are expressed as percentage reductions for those analytes which were present in the aerosol of at least one conventional waterpipe variant.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4637991/v1/97e43c583d757bd058d49114.png"},{"id":60896274,"identity":"7d124772-f51b-4b47-b553-606284fdf9ef","added_by":"auto","created_at":"2024-07-23 09:56:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":110805,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy Product Aerosol Yields Based on Estimated Weekly Consumption.\u003c/strong\u003e Data are machine aerosol yields (see Table 2) for the products indicated with assumed weekly consumption of 2 waterpipe sessions per week and 20 cigarettes per day, as stated by the German Federal Institute for Risk Assessment \u003csup\u003e20\u003c/sup\u003e. Values are shown as percentages of emissions relative to emissions from 3R4F reference cigarettes. Analytes shown are nicotine and those mandated for lowering in cigarette smoke in the World Health Organization Study Group on Tobacco Product Regulation (TobReg) proposal \u003csup\u003e21\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4637991/v1/7842839dcff840d06ad36899.png"},{"id":81987451,"identity":"3ec9d805-a58f-4b24-b0ab-4d8787ccf5fb","added_by":"auto","created_at":"2025-05-05 16:02:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1930310,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4637991/v1/e52a3ad4-b9a5-4a12-a283-42db844b9469.pdf"},{"id":60896273,"identity":"35e0667e-090d-4276-a8bd-aaf52e1c72d2","added_by":"auto","created_at":"2024-07-23 09:56:18","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":671162,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4637991/v1/780fda3054cec20f3dceaeb7.pdf"}],"financialInterests":"Competing interest reported. This study was funded by Advanced Inhalation Rituals Ltd, a manufacturer of conventional shisha tobacco products and of the OOKA electronic waterpipe and associated shisha tobacco pods. PJW, AC and RB are employees of Advanced Inhalation Rituals Ltd. IMF is a Non Executive Director with Advanced Inhalation Rituals Ltd, an independent consultant to tobacco and nicotine product manufacturers and contract research organisations, and a retained Scientific Advisory Board member of Qnovia, LLC. IMF holds shares in British American Tobacco and Qnovia, LLC.","formattedTitle":"Emissions from Conventional and Electronic Waterpipes Relative to Cigarettes and a Heated Tobacco Product","fulltext":[{"header":"introduction","content":"\u003cp\u003eWaterpipe smoking is a form of tobacco use which although global is particularly prevalent in Middle Eastern, Eastern Mediterranean and Eastern European countries\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Waterpipe use involves heating shisha, a mixture which includes tobacco, flavourings, glycerol and sweeteners. The heat source for waterpipe is most commonly wood or coconutderived charcoal briquettes, which are placed on top of the shisha in the bowl or head of the waterpipe, typically separated by a layer of aluminium foil, and lit\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. During use, puffing on the mouthpiece of the waterpipe hose draws air over the charcoal and through the shisha, and the resulting aerosol is bubbled through water before being inhaled by the user\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. This bubbling potentially removes some of the smoke toxicants, though its primary purpose is to cool the smoke prior to inhalation\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe health risks associated with the use of smoked tobacco products, including waterpipe, arise due to the inhalational exposure of harmful and potentially harmful constituents (HPHCs) and other toxicants\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, which may be harmful to the cardiovascular and respiratory systems and may also be carcinogenic\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. These toxicants are either present in the tobacco itself and transferred into the smoke during heating or generated during the processes of pyrolysis and combustion\u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. However, the largest mass of toxicants present in waterpipe smoke, which include polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene and carbon monoxide (CO), are contributed by the smouldering charcoal\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Other toxicants such as acrolein may be generated upon heating of glycerol and sugars in the shisha tobacco\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGiven the association between toxicant generation, exposure, and health risks among tobacco product users, the aim of this study was to assess the levels of HPHCs and other toxicants in aerosols generated from waterpipe heated using different means, including wood and coconutderived charcoal heating, coconutderived charcoal heating in the presence of a heat management device (HMD), and electronic heating. The study addresses a call for more research into emissions from conventionally and electronicallyheated waterpipes\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and provides muchneeded information concerning the toxicant exposure and the potential for health risks associated with waterpipe use. We additionally assessed toxicant levels in aerosol from the IQOS 3.0 heated tobacco product (HTP), and our findings are placed into context using literature data on 3R4F reference cigarette smoke toxicant levels\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003eStudy Products Emissions Yields\u003c/h2\u003e\n \u003cp\u003eData concerning absolute yields of the 37 analytes assessed in the machinegenerated emissions from 3R4F reference cigarettes, the IQOS 3.0 HTP used with TEREA Teak sticks, the conventional PM1 shisha smoking machine used with wood and coconutderived charcoal and also with a HMD, and the OOKA electronic waterpipe, are presented in Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e. These values are presented as weight per session (waterpipe products) or weight per stick (3R4F reference cigarettes and IQOS 3.0 HTP). Graphical representation of the percentage reductions in analyte yields in electronic waterpipe aerosol compared to yields in the three conventional waterpipe aerosols can be found in Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e, for those analytes which were detected in conventional waterpipe aerosols. In addition, emissions yields data are presented as weight per puff volume concentrations in Supplementary Table\u0026nbsp;3.\u003c/p\u003e\n \u003cp\u003e\u003cimg 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\"\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u003cstrong\u003eAbsolute Yields of Emission Analytes from Conventional and Electronic Waterpipe, Reference Cigarettes, and a Heated Tobacco Product.\u003c/strong\u003e Data are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD from 3 replicates. \u003csup\u003ea\u003c/sup\u003eData taken from those reported by Eldridge \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan\u003e19\u003c/span\u003e\u003c/sup\u003e. \u003csup\u003eb\u003c/sup\u003eBased on 2 replicates. \u003csup\u003ec\u003c/sup\u003eAverage yield when HMD used with 0%, 50% and 100% ventilation settings.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConventional Waterpipe Heated with WoodDerived Charcoal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConventional Waterpipe Heated with CoconutDerived Charcoal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConventional Waterpipe Heated with CoconutDerived Charcoal within a HMD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOOKA Electronic Waterpipe\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIQOS 3.0 (ILUMA) HTP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3R4F Reference Cigarette\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAnalyte\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eYield\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTCM (mg/session)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5224\u0026thinsp;\u0026plusmn;\u0026thinsp;155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4492\u0026thinsp;\u0026plusmn;\u0026thinsp;388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3842\u0026thinsp;\u0026plusmn;\u0026thinsp;509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3257\u0026thinsp;\u0026plusmn;\u0026thinsp;354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTPM (mg/stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater (mg/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2936.1\u0026thinsp;\u0026plusmn;\u0026thinsp;123.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2638.9\u0026thinsp;\u0026plusmn;\u0026thinsp;215.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2509.9\u0026thinsp;\u0026plusmn;\u0026thinsp;315.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2079.2\u0026thinsp;\u0026plusmn;\u0026thinsp;142.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNicotine (mg/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNFDPM (mg/stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlycerol (mg/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1426.7\u0026thinsp;\u0026plusmn;\u0026thinsp;31.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1107.9\u0026thinsp;\u0026plusmn;\u0026thinsp;47.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e750.0\u0026thinsp;\u0026plusmn;\u0026thinsp;164.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e786.2\u0026thinsp;\u0026plusmn;\u0026thinsp;31.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropylene Glycol (mg/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCO (mg/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e354.1\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e224.2\u0026thinsp;\u0026plusmn;\u0026thinsp;30.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.4\u0026thinsp;\u0026plusmn;\u0026thinsp;47.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBenzo[a]pyrene (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.7\u0026thinsp;\u0026plusmn;\u0026thinsp;27.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFormaldehyde (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e833\u0026thinsp;\u0026plusmn;\u0026thinsp;126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e864\u0026thinsp;\u0026plusmn;\u0026thinsp;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e589\u0026thinsp;\u0026plusmn;\u0026thinsp;69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e156\u0026thinsp;\u0026plusmn;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcetaldehyde (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1275\u0026thinsp;\u0026plusmn;\u0026thinsp;156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e979\u0026thinsp;\u0026plusmn;\u0026thinsp;72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e789\u0026thinsp;\u0026plusmn;\u0026thinsp;183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e162\u0026thinsp;\u0026plusmn;\u0026thinsp;23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1235\u0026thinsp;\u0026plusmn;\u0026thinsp;39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcetone (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e477\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e191\u0026thinsp;\u0026plusmn;\u0026thinsp;152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e222\u0026thinsp;\u0026plusmn;\u0026thinsp;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e576\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcrolein (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e368\u0026thinsp;\u0026plusmn;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166\u0026thinsp;\u0026plusmn;\u0026thinsp;108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e349\u0026thinsp;\u0026plusmn;\u0026thinsp;129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropionaldehyde (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e187\u0026thinsp;\u0026plusmn;\u0026thinsp;27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e145\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e129.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrotonaldehyde (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2Butanone (\u0026micro;g/per session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eButyraldehyde (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108\u0026thinsp;\u0026plusmn;\u0026thinsp;93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNNN (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e311.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNAT (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323.0\u0026thinsp;\u0026plusmn;\u0026thinsp;22.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNAB (ng/session or stick puffs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNNK (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e309.6\u0026thinsp;\u0026plusmn;\u0026thinsp;27.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e1,3Butadiene (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsoprene (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1042.0\u0026thinsp;\u0026plusmn;\u0026thinsp;76.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcrylonitrile (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBenzene (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e541.0\u0026thinsp;\u0026plusmn;\u0026thinsp;47.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e246.4\u0026thinsp;\u0026plusmn;\u0026thinsp;62.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eToluene (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e174.1\u0026thinsp;\u0026plusmn;\u0026thinsp;24.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.6\u0026thinsp;\u0026plusmn;\u0026thinsp;46.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e164.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e1Aminonaphthalene (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2Aminonaphthalene (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3Aminobiphenyl (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4Aminobiphenyl (ng/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmmonia (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110.0\u0026thinsp;\u0026plusmn;\u0026thinsp;25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhenol (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003em, pCresol (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eoCresol (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCatechol (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e591.6\u0026thinsp;\u0026plusmn;\u0026thinsp;65.1\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e615.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e485.6\u0026thinsp;\u0026plusmn;\u0026thinsp;61.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e161.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eResorcinol (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHydroquinone (\u0026micro;g/session or stick)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e402.6\u0026thinsp;\u0026plusmn;\u0026thinsp;55.7\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e278.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e374.9\u0026thinsp;\u0026plusmn;\u0026thinsp;46.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eAbbreviations: SD, standard deviation; HTP, heated tobacco product; HMD, heat management device; TCM, total collected matter; TPM, total particulate matter; NFDPM, nicotinefree dry particulate matter; CO, carbon monoxide; NNN, \u003cem\u003eN\u003c/em\u003e\u0026rsquo;nitrosonornicotine; NAT, \u003cem\u003eN\u003c/em\u003e\u0026rsquo;nitrosoanatabine; NAB, \u003cem\u003eN\u003c/em\u003enitrosoanabasine ; NNK, 4(methylnitrosamino)-1(3pyridyl)-1butanone; NA, not applicable; ND, not determined.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eCompared with cigarette smoke and HTP aerosol, some analytes were present in aerosol from the conventional waterpipe variants at higher levels when examined on a per stick/per session basis. For CO and glycerol, these arise due to the method of heating and the level of the humectant in the shisha tobacco, respectively. Of note, waterpipe aerosol CO yields were lower when using coconutderived, as opposed to woodderived charcoal as a heating source, and were lowered even further by the use of a HMD. Furthermore, CO was completely absent in aerosol generated from the electronic waterpipe due to it operating at temperatures lower than those which support combustion, and present at extremely low levels in HTP aerosol. The tobaccospecific nitrosamines (TSNAs) NNN, NNK, NAT and NAB were detected in 3R4F reference cigarette smoke at high levels but were not detected in the aerosol from either the conventional waterpipe variants or the electronic waterpipe. Of the TSNAs, only NAT was detected, at low levels, in IQOS 3.0 aerosol.\u003c/p\u003e\n \u003cp\u003eOf the aldehydes assessed, formaldehyde was detected in aerosol from the conventional waterpipe variants at levels greater than those in 3R4F reference cigarette smoke. While this was also the case for the electronic waterpipe, formaldehyde levels in the electronic waterpipe aerosol were approximately 74\u0026ndash;82% lower than those in conventional waterpipe aerosol. Formaldehyde was detected in HTP aerosol at levels approximately 90% lower than those in 3R4F reference cigarette smoke. Acetaldehyde was detected in conventional waterpipe aerosol at levels similar to, or lower than, those in 3R4F reference cigarette smoke depending on the charcoal used or the presence of the HMD. Acetaldehyde levels in electronic waterpipe aerosol were approximately 75% lower than those in cigarette smoke, and between approximately 61% and 76% lower than the levels in conventional waterpipe aerosol. Acrolein was detected at levels in conventional waterpipe aerosol at levels higher than those in 3R4F reference cigarette smoke, and the levels were dependent on the type of charcoal used. This analyte was detected in electronic waterpipe aerosol at levels approximately 89% lower than in cigarette smoke and between approximately 91% and 96% lower than levels in conventional waterpipe aerosol. Other aldehydes including propionaldehyde, crotonaldehyde and butyraldehyde were present in aerosols from some of the conventional waterpipe variants assessed, and at levels of the same magnitude as those in 3R4F reference cigarette smoke but were absent in aerosol from the electronic waterpipe.\u003c/p\u003e\n \u003cp\u003eOther analytes detected in conventional waterpipe aerosols at levels comparable to or higher than those in 3R4F reference cigarette smoke include benzene, toluene and ammonia, three analytes which were absent in electronic waterpipe and HTP aerosols. Phenol was present in the conventional waterpipe aerosols at levels higher than those in 3R4F reference cigarette smoke but was absent in the electronic waterpipe aerosol. Some analytes, including 1,3butadiene, isoprene, acrylonitrile, and cresols, were detected in cigarette smoke but were absent in the aerosols of all other products tested.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003eEstimated Weekly Emissions Yields\u003c/h2\u003e\n \u003cp\u003eBased on assumed weekly consumption of 2 waterpipe sessions per week and 20 cigarettes per day as stated by the German Federal Institute for Risk Assessment\u003csup\u003e\u003cspan\u003e20\u003c/span\u003e\u003c/sup\u003e, absolute emissions yields on a per session (conventional and electronic waterpipe) or a per stick (IQOS 3.0 and 3R4F reference cigarettes) basis were used to calculate estimated weekly emissions yields. Data arising from this analysis are presented for nicotine and the nine analytes mandated for lowering in cigarette smoke in the World Health Organization (WHO) Study Group on Tobacco Product Regulation (TobReg) proposal\u003csup\u003e\u003cspan\u003e21\u003c/span\u003e\u003c/sup\u003e in Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e, expressed as percentage estimated weekly yields from conventional and electronic waterpipes relative to yields from 3R4F reference cigarettes. Weekly estimated nicotine yields from the conventional waterpipe variants, and also from the electronic waterpipe, were vastly lower than those from both the reference cigarette and the HTP. Of the TobReg analytes, NNN, NNK and 1,3butadiene were absent in conventional and electronic waterpipe emissions and HTP aerosol and their estimated weekly yields were therefore zero.\u003c/p\u003e\n \u003cp\u003eOf the aldehydes, weekly estimated acrolein yields from the conventional waterpipe variants were estimated at between 4.1% and 1.9%, and for the electronic waterpipe 0.2%, of the reference cigarette yield. Weekly acetaldehyde yields were approximately 1% of reference cigarette yields for the conventional waterpipe variants, 0.35% for the electronic waterpipe, and approximately 13% for the HTP. Formaldehyde yields ranged between approximately 10% and 17% of reference cigarette yields for the HTP and the conventional waterpipe variants, and approximately 3% for the electronic waterpipe.\u003c/p\u003e\n \u003cp\u003eFor other TobReg analytes, benzene and benzo[a]pyrene estimated weekly yields were zero for both the electronic waterpipe and the HTP and for the conventional waterpipe variants ranged from 7.8\u0026ndash;0.8% of reference cigarette estimated weekly yields. Finally, relative to the reference cigarette weekly estimated yield, the CO yield was approximately 0.6% for the HTP, and zero for the electronic waterpipe due to the absence of this analyte in electronic waterpipe aerosol. The weekly estimated CO yield for the conventional waterpipe variants ranged from approximately 3\u0026ndash;16% of the reference cigarette yield.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study assessing aerosol yields from conventional and electronic waterpipes, a HTP, and a reference cigarette, our findings suggest that conventional waterpipe may expose users to lower levels of HPHCs and other harmful toxicants than combusted tobacco cigarettes. For a number of analytes, including the TobReg analytes CO, benzo[a]pyrene, formaldehyde, acetaldehyde, benzene and acrolein, we also demonstrate that the potential for exposure during conventional waterpipe use can be reduced either by using different types of charcoal or by placing the charcoal in a HMD on top of the shisha head before the charcoal is lit. However, while the use of different charcoals and/or a HMD may reduce the infiltration of toxicants such as CO into the conventional waterpipe aerosol, they are still present in substantial amounts. Heating the shisha tobacco by electronic means further reduces the levels of, or removes, these toxicants. In the case of CO, benzo[a]pyrene, propionaldehyde, crotonaldehyde, 2butanone, butyraldehyde, benzene, toluene and phenol, all were absent in the electronic waterpipe aerosol. Overall, our findings suggest that conventional waterpipe is a relatively low exposure and potentially low toxicity heated tobacco product, in which the aerosol is contaminated by toxicants arising from combustion of the charcoal or charring of the shisha tobacco. This contamination can be mitigated and/or eliminated by various means such as using different charcoal or a HMD, or by heating the shisha tobacco by electronic means at temperatures lower than those which support combustion.\u003c/p\u003e \u003cp\u003eOur findings generally concur with those in the extant literature, including chemistry assessments which have reported lower levels of acrolein and crotonaldehyde in charcoalheated shisha compared with cigarette smoke, and the absence of NNK, NNN and benzo[a]pyrene, in waterpipe aerosol\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Our findings also concur with clinical studies which have reported lower exposure to HPHCs and other toxicants among waterpipe users compared with cigarette smokers\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Regarding our findings for the electronic waterpipe, Hourani \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e reported substantial reductions in levels of PAHs (80% reduction) and CO (90% reduction) in aerosols generated from waterpipes which used electrical heating elements compared with aerosol levels from waterpipe which used conventional charcoal heating. In our study, PAHs including benzo[a]pyrene, 1aminonapthalene and 2aminonapthelene, and CO, were detected in conventional waterpipe aerosol but were absent in electronic waterpipe aerosol. In contrast to the previous study however, Hourani \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e reported that the levels of volatile aldehydes such as acrolein were severalfold higher in the waterpipe heated using an electrical heating element compared with conventional charcoalheated waterpipe. In our study, aerosol aldehyde yields of formaldehyde, acetaldehyde, acrolein, propionaldehyde, crotonaldehyde and butyraldehyde were substantially lower in electronic waterpipe aerosol, with those reductions, depending on the conventional waterpipe assessed, ranging from approximately 62% for acetaldehyde to 100% for propionaldehyde, crotonaldehyde and butyraldehyde. For formaldehyde and acrolein, percentage reductions were between approximately 74% and 82% and between approximately 91% and 96%, respectively, depending on the conventional waterpipe heating method. The reasons for these differences are unclear. One potential reason is that the electronic waterpipe used in our study uses precise temperature control which the aftermarket electrical heating elements for conventional waterpipe used by Hourani \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e may not provide. Such uncontrolled heating may increase the levels of aldehydes, which can be formed as thermal breakdown products of the humectants propylene glycol and glycerol\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e which are used as additives in shisha tobacco\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is important, when undertaking both absolute and relative human health risk assessments of tobacco and nicotine products, and to understand any risks associated with realworld use, to take use patterns such as quantity and frequency of use into account\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. In this paper, we utilised our aerosol yield data and integrated this with estimated average consumption patterns (2 waterpipe sessions per week and 20 cigarettes per day\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e) to generate an overall assessment of the potential for exposure to nicotine and the nine analytes mandated for lowering in cigarette smoke in the WHO TobReg proposal\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Using this approach, we demonstrated that overall exposure associated with the use of conventional waterpipe, electronic waterpipe, and the IQOS HTP, was either substantially reduced or eliminated for the analytes assessed. This has the potential to mitigate the health risks associated with tobacco product use, although due to the nonlinearity of the exposureresponse the degree of risk mitigation cannot be estimated\u003csup\u003e\u003cspan additionalcitationids=\"CR32 CR33\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. These exposure mitigations are however likely to have implications for both individual and population health. For example, \u003cem\u003ein vitro\u003c/em\u003e and animal studies have demonstrated a reduced toxicological and pathological impact of waterpipe aerosol compared with cigarette smoke\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. In human clinical studies, the reduced exposure profile of the IQOS HTP has been shown to result, at least in the short to mediumterm, in beneficial changes in indicators of disease risk\u003csup\u003e\u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e, though similar studies have not been conducted for waterpipes.\u003c/p\u003e \u003cp\u003eImportantly, our emissions analysis, as well as data in the literature, may serve to correct certain misperceptions regarding waterpipe use\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. Firstly, it has been reported that waterpipe tobacco has a significantly higher nicotine content than cigarettes, with one head of shisha tobacco reportedly containing the nicotine equivalent of 70 cigarettes\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. In this paper, while we report that the nicotine concentration in the aerosol from both conventional and electronic waterpipe was approximately 2 to 4times higher than that in 3R4F reference cigarette smoke when assessed on a per session or per stick basis. However, it has to be considered that waterpipe use sessions last much longer than cigarette smoking sessions and include substantially more puffs\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. When these factors are taken into account, aerosol nicotine content on an amount per puff volume or on a per puff basis are substantially lower for conventional waterpipe compared with cigarettes, and even lower for the OOKA electronic waterpipe assessed in the study. This is supported by previous findings that waterpipe use was associated with significantly lower intake of nicotine\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and this is also associated with significantly lower exposure to NNK, naphthalene, fluorene, acrylonitrile, acrolein, 1\u0026ndash;3,butadiene and other toxicants among waterpipe users compared with cigarette smokers\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. It has also been asserted that smoke exposure from a single waterpipe session could be as much as that from 100\u0026ndash;200 cigarettes\u003csup\u003e\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. This contrasts with the findings of this study, in which the greatest difference between the levels of a toxicant, formaldehyde, in conventional waterpipe aerosol compared with cigarette smoke on an amount per puff volume or on a per puff basis was a 10fold difference. Furthermore, this does not take into account typical use patterns to arrive at a human health risk estimate, as undertaken in this study, based on realworld emissions yields and potential for exposure. When taking use patterns into account, out data suggest that the potential for overall exposure to HPHCs and other toxicants associated with waterpipe use are likely to be substantially lower than potential exposure due to cigarette smoking.\u003c/p\u003e \u003cp\u003eOur study and its findings are subject to some limitations. Firstly, for the conventional waterpipe we assessed emissions using a standardised shisha smoking machine, two different types of charcoal, a HMD, and a single type of shisha tobacco. Our findings may not be generalisable to the many different types of conventional waterpipes, charcoals, HMDs, and shisha tobaccos, that are available to consumers. In addition, the OOKA electronic waterpipe assessed in this study, which heats a shisha tobacco blend very similar in composition to the shisha tobacco used for conventional waterpipe aerosol generation, is a very different device than \u0026lsquo;eshisha\u0026rsquo; or \u0026lsquo;ehookah\u0026rsquo; devices. The majority of ehookah devices operate in a manner not dissimilar to electronic cigarettes\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e and use a metallic coil to vaporise an eliquid solution which is flavoured to mimic the taste of shisha\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Given the marked dissimilarity between the electronic waterpipe assessed in this study and \u0026lsquo;ehookah\u0026rsquo;, our findings cannot be extrapolated to ehookah devices. Secondly, our study used a standardised puffing regimen to generate aerosols for all the products assessed. Realworld use patterns, in which users puff on the waterpipe differently to the puffing regimen prescribed by the ISO regimen used in this study, may give rise to different aerosol toxicant yields, as has been reported both for waterpipe\u003csup\u003e\u003cspan additionalcitationids=\"CR47\" citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e and other tobacco/nicotine products\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Thirdly, our reported relative differences in machinederived aerosol toxicant yields may not be indicative of actual relative exposure, and human clinical studies assessing biomarkers of exposure are required in order to assess relative exposure from different types of tobacco products and different waterpipe heating methods. That said, our finding that a number of HPHCs and other toxicants are absent in machinederived conventional and electronic waterpipe aerosols can be assumed to lead to an absence of exposure. Fourthly, we only measured 37 analytes in the tobacco product aerosols, and our findings are therefore limited to potential exposure to those chemicals.\u003c/p\u003e \u003cp\u003eIn summary, conventional waterpipe aerosol contains fewer, and lower levels of, a number of HPHCs and other toxicants relative to combustible cigarette smoke, both when assessed as analyte levels and also when taking into account typical use patterns. The levels of toxicants can be reduced either by using different types of charcoal or by using a HMD. In addition, heating the shisha tobacco by electronic means in the OOKA waterpipe drives toxicant levels down even further, and many of these toxicants, such as CO, acetaldehyde, acrolein, benzene and benzo[a]pyrene, are absent from the OOKA electronic waterpipe aerosol. These findings have important implications for understanding toxicant yields and potential exposure among waterpipe users, and for understanding how to potentially reduce the health risks associated with waterpipe use. Furthermore, similar to the manner in which innovation in electronic tobacco heating in HTPs may reduce the health risks associated with cigarette smoking, applying similar principles to waterpipe use, and using innovative non-combusting heating methods, can potentially reduce harms associated with waterpipe use.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eStudy Products\u003c/p\u003e\n\u003cp\u003eImages of the products assessed in this study can be found in Supplementary Table\u0026nbsp;1. Conventional waterpipe emissions were generated using a PM1 shisha smoking machine (K\u0026ouml;rber Technologies Instruments, Hamburg, Germany), a smoking machine specifically designed for the smoking of shisha tobacco. The shisha tobacco used was \u0026ldquo;Two Apples\u0026rdquo; (Al Fakher, Dubai, UAE). The charcoals used were Quick Light beech woodderived charcoal (Three Kings, Bladel, Netherlands) and BLACKCOCO\u0026rsquo;s CUBES26 coconutderived charcoal (BLACKCOCO\u0026rsquo;s GmbH, Heilbronn, Germany). The HMD used was a Lotus device (Kaloud, CA, US), which is comprised of an aluminium vessel in which the charcoal is placed. This vessel is then housed on the head of the waterpipe, approximately 3 mm above the shisha tobacco and controls the transfer of heat to the tobacco. The combustible cigarette was a Kentucky 3R4F reference cigarette (University of Kentucky, KY, US). The HTP used was an IQOS 3.0 device (\u0026ldquo;ILUMA\u0026rdquo;; Philip Morris International (PMI), Lausanne, Switzerland), used with TEREA \u0026ldquo;Teak\u0026rdquo; tobacco sticks (PMI) which are specifically designed for use with the IQOS 3.0 inductive heating HTP. The electronic waterpipe used was an OOKA waterpipe with \u0026ldquo;Two Apples\u0026rdquo; OOKA pods (Advanced Inhalation Rituals, Dubai, UAE), which were selected since they contain a shisha tobacco blend very similar in composition to the shisha tobacco used for conventional waterpipe aerosol generation. Unlike conventional shisha, which uses heat convection through the air stream and heat radiation from the bottom of the foil, OOKA uses heat conduction to heat the shisha molasses. OOKA has a thin-film heating element on the wall of a micro-oven which conducts heat into the OOKA pod. Sensors placed around the micro-oven allow the temperature to be accurately measured allowing the OOKA to rapidly modify the heat energy inside the pod to reduce accidental overheating associated with conventional charcoalheated waterpipes.\u003c/p\u003e\n\u003cp\u003ePM1 Shisha Smoking Machine Preparation\u003c/p\u003e\n\u003cp\u003eA 10 g sample of shisha tobacco was placed into the head of the PM1 shisha smoking machine. The head was covered in aluminium foil and a puncher used to create uniform perforations. Either wood or coconutderived charcoal was placed centrally on the foil and lit using a gas lighter. The waterpipe head was connected to the bottle containing 750 ml deionized water, as per International Organisation for Standardisation (ISO) Technical Specification 22486 \u0026ldquo;Water pipe tobacco smoking machine - Definitions and standard conditions\u0026rdquo; \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. The waterpipe head was protected from ambient air currents using a glass screen, a setup which is representative of typical use by consumers. When the PM1 shisha smoking machine was used with the Lotus HMD, the same amount of shisha tobacco was placed into the shisha head, the charcoal was placed into the HMD and lit, and the HMD was placed on top of the shisha tobacco. The Lotus HMD can be set to allow different ventilation levels, and levels of 100%, 50% and 0% were used in this study. Data are presented in this paper as average yields obtained when using these three different ventilation levels.\u003c/p\u003e\n\u003cp\u003eWaterpipe Aerosol and Cigarette Smoke Collection \u0026amp; Analysis\u003c/p\u003e\n\u003cp\u003ePuffing parameters used for waterpipe aerosol/cigarette smoke generation are shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Conventional and electronic waterpipe aerosols generated using the PM1 shisha smoking machine and the OOKA electronic waterpipe were collected in a onehour session according to ISO 22486. Aerosol from the IQOS 3.0 HTP was generated using the Health Canada Intense (HCI) machine smoking regimen \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Aerosols from both conventional and electronic waterpipes, and the IQOS 3.0 HTP, were generated and analysed at ASL Analytic Service Laboratory GmbH (Hamburg, Germany), an ISO 17025 accredited laboratory. Mainstream smoke yields from 3R4F reference cigarettes were taken from a published study which generated cigarette smoke using the HCI machine smoking regimen, also at an ISO 17025 accredited laboratory \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAnalytical Methods\u003c/p\u003e\n\u003cp\u003eDetails of the analytical methods used to measure emissions analytes can be found in Supplementary Table\u0026nbsp;2.\u003c/p\u003e\n\u003ch3\u003eData Analyses\u003c/h3\u003e\n\u003cp\u003eEmissions generation and analytical chemistry assessments were performed in triplicate, unless otherwise stated. Data are presented using descriptive statistics (means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations (SD) from the three replicates). Concentrations of analytes in the emissions from the products assessed are also presented; these data were calculated from the absolute yields using total puff volumes of 92.75 l for the conventional and electronic waterpipe products (175 puffs of 530 ml volume), 0.55 l for IQOS 3.0 (11 puffs of 55 ml volume), and 0.572 0.605 l for the 3R4F reference cigarette (based on an average number of 55 ml volume puffs, depending on the analyte, reported in Eldridge \u003cem\u003eet al\u003c/em\u003e \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e). We also further present data as estimated percentage weekly emissions yields from the conventional and electronic waterpipe and the IQOS 3.0 HTP relative to estimated weekly yields from conventional cigarettes. These were derived using assumed weekly consumption of 2 waterpipe sessions per week and 20 cigarettes per day, as stated by the German Federal Institute for Risk Assessment \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the support of ASL Analytical Services Laboratory GmBH (Hamburg, Germany) in conducting the emissions generation and chemical analyses. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePJW, AC and RB designed the study. IMF assessed and contextualized the data and wrote the initial draft manuscript. All authors contributed to editing and approving the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during the study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Advanced Inhalation Rituals Ltd, a manufacturer of conventional shisha tobacco products and of the OOKA electronic waterpipe and associated shisha tobacco pods. PJW, AC and RB are employees of Advanced Inhalation Rituals Ltd. IMF is a Non‑Executive Director with Advanced Inhalation Rituals Ltd, an independent consultant to tobacco and nicotine product manufacturers and contract research organisations, and a retained Scientific Advisory Board member of Qnovia, LLC. IMF holds shares in British American Tobacco and Qnovia, LLC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Advanced Inhalation Rituals Ltd.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlmomen, S.\u003cem\u003e et al.\u003c/em\u003e Effect of glycerol concentration on levels of toxicants emissions from water-pipe tobacco smoking (WTS). \u003cem\u003eBMC Public Health\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 1858, doi:10.1186/s12889-023-16740-2 (2023).\u003c/li\u003e\n\u003cli\u003eKienhuis, A. S. \u0026amp; Talhout, R. 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(2019).\u003c/li\u003e\n\u003cli\u003eGovernment of Canada. \u003cem\u003eTobacco reporting regulations. SOR/2000-273\u003c/em\u003e, \u0026lt;https://laws-lois.justice.gc.ca/PDF/SOR-2000-273.pdf\u0026gt; (2000).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hookah, waterpipe, shisha, electronic waterpipe, cigarette, heated tobacco product","lastPublishedDoi":"10.21203/rs.3.rs-4637991/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4637991/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHarms associated with tobacco product use, including waterpipe, are due to inhalational exposure to toxicants either present in tobacco or formed during the process of combustion. We assessed levels of 37 toxicants in aerosol emissions from conventional waterpipe heated with different charcoals and also with a heat management device (HMD), from the IQOS heated tobacco product (HTP), and the \u0026lsquo;OOKA\u0026rsquo; electronic waterpipe. We also utilised literature data on toxicant yields in 3R4F reference cigarette smoke. When taking use patterns into account, toxicant yields were substantially lower in conventional waterpipe aerosol compared with cigarette smoke. Toxicant yields in electronic waterpipe aerosol were substantially lower than those in conventional waterpipe aerosol, both on a per session basis and when taking typical use patterns into account. Numerous toxicants in conventional waterpipe aerosol were absent in electronic waterpipe aerosol. In summary, during typical use conventional waterpipe emits fewer, and lower levels of, a number of toxicants relative to combustible cigarette smoke. In addition, electronically heating shisha further reduces toxicant levels, and many toxicants are absent in OOKA electronic waterpipe aerosol. These findings have important implications concerning toxicant exposure among waterpipe users, and for understanding how to potentially reduce health risks associated with waterpipe use.\u003c/p\u003e","manuscriptTitle":"Emissions from Conventional and Electronic Waterpipes Relative to Cigarettes and a Heated Tobacco Product","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 09:56:13","doi":"10.21203/rs.3.rs-4637991/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-08T05:41:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-31T07:09:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265188556599417494581922584938116345006","date":"2024-08-21T05:58:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-29T00:15:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165801700182903767040577972154126243452","date":"2024-07-10T12:01:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-05T09:06:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-05T09:04:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-01T12:40:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-01T12:37:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-25T16:58:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"57d08fcb-aef6-4dfe-b4fd-4d1fb6325c31","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T15:58:43+00:00","versionOfRecord":{"articleIdentity":"rs-4637991","link":"https://doi.org/10.1038/s41598-025-90721-w","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-04-30 15:57:04","publishedOnDateReadable":"April 30th, 2025"},"versionCreatedAt":"2024-07-23 09:56:13","video":"","vorDoi":"10.1038/s41598-025-90721-w","vorDoiUrl":"https://doi.org/10.1038/s41598-025-90721-w","workflowStages":[]},"version":"v1","identity":"rs-4637991","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4637991","identity":"rs-4637991","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}