The available data suggest that smokers partially compensate for a different smoke yield. While the factors and their interaction responsible for compensational smoking are not fully understood, there are data suggesting that a subgroup of smokers may partially compensate for nicotine. Even in this subgroup of smokers, however, the relative importance of the pharmacological versus

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Children are at a higher risk of developing an atopic eczema when exposed to ETS and genetically predisposed children are at higher risk of developing a sensitization against house dust mites.

Summary With increasing use of new generation tobacco/nicotine products (TNPs) instead or in addition to conventional cigarettes (CCs), the question arises, whether the user of these new TNPs and CCs can be distinguished on the basis of their exposure in terms of intake and uptake of specific chemicals. For this purpose, the exposure to chemicals for users of 5 product types including CCs, HNB (heat-not-burn products), electronic cigarettes (ECs), oral tobacco products (OT, with the focus on snus), nicotine replacement therapy (NRT) products (only nicotine gum (NG) was considered in this study) was evaluated on the basis of published data. For both intake and biomarker-based uptake, 4 relative exposure levels with the assigned values from 1 (lowest exposure) to 4 (highest exposure) were defined resulting in exposure level patterns. Unique single-biomarker-based exposure levels were found for smokers (11 chemicals), vapers (1 chemical) and non-users (NU, 1 chemical). A few selected biomarkers (usually with relative levels of 3–4) were found to be sufficient for unequivocal differentiation of one user/NU group from the other 5 groups. The impact of dual-product use is also briefly discussed. [Contrib. Tob. Nicotine Res. 30 (2021) 167–198]

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Aromatic amines (arylamines) such as o-toluidine, 2-aminonaphthalene, and 4-aminobiphenyl occur in the environment and are constituents of tobacco smoke. Human exposure to these aromatic amines has long been associated with an elevated risk of bladder cancer. A validated, specific, and sensitive method for measuring o-toluidine, 2-aminonaphthalene, and 4-aminobiphenyl in cigarette smokers and nonsmokers was developed. The method uses acid hydrolysis of the arylamine conjugates in urine, extraction with n-hexane, derivatization with pentafluoropropionic anhydride, and subsequent analysis with gas chromatography combined with mass spectrometry using negative ion chemical ionization. The limits of detection were 4 ng/L for o-toluidine and 1 ng/L for 2-aminonaphthalene and 4-aminobiphenyl. Smokers (N = 10) excreted significantly higher amounts of o-toluidine (204 versus 104 ng/24 h), 2-aminonaphthalene (20.8 versus 10.7 ng/24 h), and 4-aminobiphenyl (15.3 versus 9.6 ng/24 h) than nonsmokers (N = 10). Urinary arylamine excretion in smokers was associated with the extent of smoking as assessed by daily cigarette consumption, urinary excretion of nicotine equivalents (nicotine plus its five major metabolites), cotinine in saliva, and carbon monoxide in exhaled breath. All nonsmokers investigated had quantifiable amounts of o-toluidine, 2-aminonaphthalene, and 4-aminobiphenyl in their urine, confirming that other environmental sources of exposure to these compounds also occur. In conclusion, the analytical method is suitable for measuring short-term exposure to arylamines in urine of non-occupationally exposed smokers and nonsmokers.

Mercapturic acids (MAs) are metabolic end products formed from conjugates between glutathione and electrophilic compounds. MAs are, therefore, suitable biomarkers of exposure to toxicants, which are either electrophiles by themselves or metabolized to electrophilic intermediates. We developed and validated two LC-MS/MS methods which allow the complementary, rapid, and sensitive determination of MAs derived from acrolein, acrylamide, acrylonitrile, benzene, 1,3-butadiene, crotonaldehyde, N,N-dimethylformamide, ethylene, ethylene oxide, vinyl chloride, propylene oxide, styrene, toluene as well as methylating and ethylating agents. Since separate determinations of single or small groups of MAs are time-consuming and expensive, we multiplexed several individual methods into two LC-MS/MS methods covering 18 individual mercapturic acids. Method validation according to FDA guidelines showed excellent results in terms of robustness, accuracy, and sensitivity of the methods. Moreover, the use of a minimal, simple, and straightforward sample cleanup procedure further accelerated the analytical workflow, which allows a time- and cost-efficient analysis of up to 18 MAs derived from various toxicants in environmental levels. The methods were applied to urine samples derived from a strictly diet-controlled clinical study, including 25 smoking and 25 non-smoking subjects. Significant increase in the urine concentrations in smokers as compared to non-smokers (p < 0.01; Student t test) was observed for 13 individual MAs. Moreover, a dose dependence was obtained for the majority of the analytes. In conclusion, the newly developed assays represent a powerful tool for the fast and reliable quantification of 18 MAs in clinical studies. A first method application suggests several suitable biomarkers for nine relevant toxicants in tobacco smoke.

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