Cigarette smoke (CS) affects immune functions, leading to severe outcomes in smokers. Robust evidence addresses the immunotoxic effects of combustible tobacco products. As heat-not-burn tobacco products (HNBT) vaporize lower levels of combustible products, we here compared the effects of cigarette smoke (CS) and HNBT vapor on Jurkat T cells. Cells were exposed to air, conventional cigarettes or heatsticks of HNBT for 30 min and were stimulated or not with phorbol myristate acetate (PMA). Cell viability, proliferation, reactive oxygen species (ROS) production, 8-OHdG, MAP-kinases and nuclear factor κB (NFκB) activation and metallothionein expression (MTs) were assessed by flow cytometry; nitric oxide (NO) and cytokine levels were measured by Griess reaction and ELISA, respectively. Levels of metals in the exposure chambers were quantified by inductively coupled plasma mass spectrometry. MT expressions were quantified by immunohistochemistry in the lungs and liver of C57Bl/6 mice exposed to CS, HNBT or air (1 h, twice a day for five days: via inhalation). While both CS and HBNT exposures increased cell death, CS led to a higher number of necrotic cells, increased the production of ROS, NO, inflammatory cytokines and MTs when compared to HNBT-exposed cells, and led to a higher expression of MTs in mice. CS released higher amounts of metals. CS and HNBT exposures decreased PMA-induced interleukin-2 (IL-2) secretion and impaired Jurkat proliferation, effects also seen in cells exposed to nicotine. Although HNBT vapor does not activate T cells as CS does, exposure to both HNBT and CS suppressed proliferation and IL-2 release, a pivotal cytokine involved with T cell proliferation and tolerance, and this effect may be related to nicotine content in both products.

This study aimed to elucidate the origin of the widespread nicotine contamination of plant-derived commodities, by conducting field experiments with various herbs and spice plants. By scattering tobacco and cigarette butts on the field and subsequent nicotine analyses of the acceptor plants, we verified that the alkaloid is leached out into the soil and is taken up by the crop plants. This path of contamination pertains even when there is only one cigarette butt per square meter. Even such minor pollution results - at least in the case of basil and peppermint - in considerable high nicotine contaminations, which exceed the maximum residue level by more than 20-fold.The data reported here clearly outline the large practical relevance of this soil-borne contamination path and imply that unthoughtful disposal of cigarette butts in the field by farm workers may be the reason for the widespread occurrence of nicotine contamination in plant-derived commodities. Therefore, such misbehavior needs to be prevented using education and sensitization, and by including this issue into the guidelines of good agricultural practice.

Quantifying population exposure level to tobacco smoke is important for investigating its adverse effects on human health. We aimed to investigate the feasibility and application of using population hair concentrations of nicotine and cotinine to indicate their exposure level to tobacco smoke among pregnant women. Our study recruited 256 mothers who delivered healthy babies and collected their hair samples from scalp, of which 172 mothers were self-reported non-passive smokers and the other 84 mothers were self-reported passive smokers. We analyzed nicotine and cotinine concentrations of the hair section grown during the early pregnancy. The linear relationship between cotinine and nicotine was developed and validated by internal cross-validation method. Our results revealed that self-reported passive smokers had higher concentrations of nicotine [2.08 (1.00–4.46) ng/mg hair, i.e. median value (inter-quartile range)] and cotinine [0.063 (0.041–0.148) ng/mg hair] than non-passive smokers [1.35 (0.58–2.59) ng/mg hair of nicotine and 0.049 (0.022–0.087) ng/mg hair of cotinine, respectively]. There existed a linear regression model between hair cotinine and nicotine concentrations, i.e. [cotinine] = 0.024 × [nicotine]+0.0184 (R2 = 0.756) for this population. The internal cross-validation squared correlation coefficient slightly increased from 0.689 to 0.734 with the training subjects varying from 20% to 90%, suggesting that this regression model had high robustness and predictive accuracy. It was concluded that nicotine in maternal hair can evaluate the hair cotinine level and reflect maternal passive exposure level to ambient tobacco smoke with high sensitivity.

Aerosols from eight e-cigarettes at different nicotine levels and flavoring were characterized as particle number size distributions in the range 5.6–560 nm by FMPS and CPC. Results were used to provide dosimetry estimates applying the MMPD model.Particle number concentrations varied between 3.26 × 109 and 4.09 × 109 part cm−3 for e-liquids without nicotine and between 5.08 × 109 and 5.29 × 109 part cm−3 for e-liquids with nicotine. No flavor effects were detected on particle concentration data. Particle size distributions were unimodal with modes between 107–165 nm and 165–255 nm, for number and volume metrics, respectively.Averagely, 6.25 × 1010 particles were deposited in respiratory tree after a single puff. Highest deposition densities and mean layer thickness of e-cigarette liquid on the lung epithelium were estimated at lobar bronchi.Our study shows that e-cigarette aerosol is source of high particle dose in respiratory system, from 23% to 35% of the daily dose of a no-smoking individual.

Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals. This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6–9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency. Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.

Although concerns have been raised about co-selection for antibiotic resistance and various antibiotics and non-antibiotic agents, the data on their association in urban sludge is still limited. In addition, antibiotic contamination can result in not only the toxicity but also the antibiotic resistance. In this study, the first large-scale identification of antibiotics and non-antibiotic agents concern for co-selection of resistance against antibiotics was conducted in urban sludge. Co-occurrence analysis showed that antibiotic resistance genes (ARGs) had no significant correlation with the corresponding antibiotics. Therefore, the results of co-occurrence analysis based on antibiotic concentration and ARG abundance were always ambiguous and difficult to interpret. However, antibiotic resistance was positively correlated with highly toxic compounds such as diclofenac, enrofloxacin and nicotine, suggesting that environmental contaminants might influence antibiotic resistance while exerting toxicity through mechanisms such as changes in microbial community and enzyme activity. The close correlation between class 1 integrase gene (intI1) and diclofenac/enrofloxacin indicated that the co-selection scenario between environmental contaminants and ARGs was likely mediated via intI1. In total, the derived co-occurrence patterns improve our understanding of the co-selection between ARGs, antibiotics and non-antibiotic agents, and also reaffirm the importance of potential role of non-antibiotic agents in the global spread of antibiotic resistance.

Chemical analysis of plasma samples of wild fish from the Sava River (Croatia) revealed the presence of 90 different pharmaceuticals/illicit drugs and their metabolites (PhACs/IDrgs). The concentrations of these PhACs/IDrgs in plasma were 10 to 1000 times higher than their concentrations in river water. Antibiotics, allergy/cold medications and analgesics were categories with the highest plasma concentrations. Fifty PhACs/IDrgs were identified as chemicals of concern based on the fish plasma model (FPM) effect ratios (ER) and their potential to activate evolutionary conserved biological targets. Chemicals of concern were also prioritized by calculating exposure-activity ratios (EARs) where plasma concentrations of chemicals were compared to their bioactivities in comprehensive ToxCast suite of in vitro assays. Overall, the applied prioritization methods indicated stimulants (nicotine, cotinine) and allergy/cold medications (prednisolone, dexamethasone) as having the highest potential biological impact on fish. The FPM model pointed to psychoactive substances (hallucinogens/stimulants and opioids) and psychotropic substances in the cannabinoids category (i.e. CBD and THC). EAR confirmed above and singled out additional chemicals of concern - anticholesteremic simvastatin and antiepileptic haloperidol. Present study demonstrates how the use of a combination of chemical analyses, and bio-effects based risk predictions with multiple criteria can help identify priority contaminants in freshwaters. The results reveal a widespread exposure of fish to complex mixtures of PhACs/IDrgs, which may target common molecular targets. While many of the prioritized chemicals occurred at low concentrations, their adverse effect on aquatic communities, due to continuous chronic exposure and additive effects, should not be neglected.

Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.

Electronic cigarette (e-cigarette) use has steadily increased since 2010. Indoor e-cigarette use exposes bystanders to a new source of particulate matter (PM) air pollution. Elevated short-term exposures to PM with a lower measuremented aerodynamic diameter (≤2.5 μm), PM₂.₅ and ultrafine particles (UFPs) have been linked to increased risk of adverse respiratory and cardiac events. This exposure study estimated concentrations of PM₂.₅ and UFPs from indoor e-cigarette use at 0.5 meters (m) and 1 m away from an e-cigarette user and investigated whether these indoor concentrations varied across three common e-cigarette models. One e-cigarette user tested three different e-cigarettes containing the same nicotine solution on three separate occasions and measured concentrations on PM₂.₅ and UFPs at 0.5 and 1 m in a ∼38 m³ office. Continuous measures of PM₂.₅ and UFPs were taken for 5.5 min before e-cigarette use, then the user puffed seven times for 6.5 min (exposure), and for 10 min after ceasing e-cigarette use. Following the initiation of e-cigarette use, levels of PM₂.₅ increased 160-fold at a distance of 0.5 m, and 103-fold at 1 m. The corresponding increases in UFP counts were 5.2, and 3.0-fold higher, respectively. The PM₂.₅ concentrations and UFP counts between e-cigarette models were statistically significantly different at 1 m, but not at 0.5 m. There was substantial variability between distances, e-cigarettes, and replicates. This study indicates that e-cigarette vapors influence PM₂.₅ and UFPs concentrations/counts at close proximity distances indoors; additional research is needed to characterize the composition of those particles and evaluate the impacts of other e-cigarette solutions on indoor air quality.