Assessment of the Exposure to Tobacco-Specific Nitrosamines and Minor Tobacco Alkaloids in Users of Various Tobacco/Nicotine Products

Abstract

Tobacco-specific nitrosamines (TSNAs), in particular, the human carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN), are important toxicants in tobacco and also (as contaminants) in nicotine products. In a clinical study comprising a period of 74 h under confinement, we investigated the exposure to NNK, NNN, N′nitrosoanabasine (NAB), and N′-nitrosoanatabine (NAT) as well as to the minor tobacco alkaloids anabasine (AB) and anatabine (AT) by measuring suitable biomarkers in habitual users of combustible cigarettes (CCs), electronic cigarettes (ECs), heated tobacco products (HTPs), oral tobacco (OT), and nicotine replacement therapy products (NRTs). Non-users (NU) of any tobacco/nicotine products served as the (negative) control group. Smokers exhibited the highest levels for all biomarkers measured, except for AB in urine, which was found to be highest in OT users. Somewhat elevated levels compared to NU, EC, and NRT groups were also observed in the users of HTPs. In the users of tobacco-containing products (CC, HTP, and OT), most frequently the biomarkers significantly correlated with the dose markers such as daily consumption, urinary nicotine equivalents (Nequ), and plasma cotinine (CotP). In conclusion, except for smokers (CC) and OT users, exposure of users of ECs, HTPs, and NRTs to TSNAs as well as the minor tobacco alkaloids AB and AT is marginal and statistically not distinguishable from that of NU. Finally, our results for NNN in the saliva provide preliminary evidence for the formation of NNN from the precursor nornicotine in the presence of thiocyanate as a catalyst. The latter hypothesis requires experimental verification.

Assessment of the Exposure to Aromatic Amines in Users of Various Tobacco/Nicotine Products

“…3-ABP and 4-ABP excretions in the night and day urine fractions of smokers (CC) showed a characteristic pattern with lower levels in the urine fractions collected overnight compared to those collected during the day. This is notably different from all urinary biomarkers of exposure in smokers (CC), where a reverse pattern (if any) was observed. ,, Reasons for this phenomenon are discussed below. Excretion levels for the five other groups (non-CC users including NU) were found to be similar with slight elevations in some urine fractions of all four aromatic amines in HTP users (Figure ).…”

“…All biomarkers which exhibited day versus night excretion rates in smokers (CC) showed higher levels in the fraction collected overnight compared to that collected during the day. 28,29,35 We explained this by the fact that about 15% more cigarettes were consumed in the time period between 3 pm and midnight (which is mainly reflected in the amounts of biomarkers in the urine fraction collected overnight and completed with the first morning urine) than in the time period between 7 am until 5 pm (when smoking was allowed and is mainly reflected in the urine fractions collected during the day). 28 This is illustrated in Figure 3, which shows the time patterns of 4-ABP in comparison to those of nicotine equivalents and 2cyanoethyl-mercaturic acid (CEMA, a biomarker for exposure to acrylonitrile).…”

“…Briefly, 10 subjects per group, which were self-reported exclusive users of the respective products for at least 6 months, were confined for 74 h to a clinic. Product use (own brands, described in more detail elsewhere , ) was allowed between 8 am and midnight during the subjects’ stay in the clinic.…”

“…The “during-the-day” urine was collected between 7 am (after the first morning urine) and 5 pm of the same day. A collection scheme for the biological samples has been published previously. − …”

Anabasine and Anatabine Exposure Attributable to Cigarette Smoking: National Health and Nutrition Examination Survey (NHANES) 2013–2014

“…This differentiation also holds true for certain nicotine products that contain low or non-detectable levels of anabasine and anatabine [ 4 ]. For example, exclusive use of e-cigarettes, heat-not-burn products, or NRT products resulted in urinary anabasine and anatabine levels that were not statistically distinguishable from non-users and were significantly lower than levels resulting from exclusive cigarette smoking [ 7 ]. Additionally, numerous products are currently marketed as containing synthetic nicotine rather than tobacco-derived nicotine; measuring urinary anabasine and anatabine could differentiate people who use “tobacco-free” nicotine from those who use other tobacco-derived nicotine products [ 5 ].…”