THR PubMed Research

Key challenges for in vitro testing of oral tobacco and nicotine products for regulatory applications: Recommendations for using in vitro toxicity and disease models

Purpose: The report aims to develop scientific and technical recommendations for in-vitro assessment of oral tobacco and nicotine products.

Scope: It provides an overview of oral products, discusses methods for generating test extracts, recommends testing practices for toxicity and disease models and identifies areas for future research.

Development: The publication was prepared by a working group associated with the ninth Institute for In Vitro Sciences workshop on oral tobacco and nicotine product testing, held in January 2024.

Source context: Listed affiliations include the Institute for In Vitro Sciences and independent or contract laboratories, as well as BAT, JT International, Altria, RAI Services Company, Swedish Match and an Imperial Brands company. This context should be considered when interpreting the recommendations.

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Current Tobacco/Nicotine Use and Pelvic Pain and Urgency/Frequency (PUF)-Defined Urinary Symptom Burden Among Lebanese University-Aged Adults: A Cross-Sectional Study

Methods: This cross-sectional study included 476 Lebanese university students and recent graduates aged 18-30. Urinary symptoms were assessed with the Pelvic Pain and Urgency/Frequency questionnaire.

Results: Current smokers represented 35.1% of the sample. Low-threshold screening-positive symptoms were present in 82.0% of smokers versus 18.1% of non-smokers. Higher-threshold symptoms were present in 40.1% versus 1.9%.

Adjusted analysis: Current smoking remained strongly associated with both symptom thresholds after adjustment for age, caffeine intake, sex, body mass index and university type. A dose-response pattern was also observed among cigarette/cigar users.

Limitation: The study was cross-sectional and questionnaire-based. The results describe screening associations rather than confirmed clinical diagnoses or proof of causation.

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The Association Between E-cigarette Use and Sleep Duration Among Adolescents and Young Adults: A Structured Narrative Review

Scope: This structured narrative review synthesised evidence on e-cigarette use, sleep duration and sleep disturbances among adolescents and young adults.

Evidence: Six empirical studies and one narrative review met the inclusion criteria.

Findings: Exclusive e-cigarette use was repeatedly associated with approximately 30-80% higher odds of insufficient sleep, while dual users generally had stronger associations and in some studies were up to three times more likely to report inadequate sleep.

Interpretation: The authors suggest nicotine-related arousal and withdrawal may contribute, but sleep problems may also increase susceptibility to vaping.

Limitation: Longitudinal and mechanistic studies are needed to determine causal pathways.

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Chronic nicotine vapor-induced enhancement of ethanol drinking-in-the-dark is associated with reduced medial prefrontal cortical activity

Purpose: The study developed a mouse model to examine how nicotine vapor exposure affects binge-like alcohol consumption and brain activity.

Results: Nicotine vapor selectively increased alcohol intake and blood ethanol concentrations without increasing consumption of the control solution.

Brain findings: Nicotine exposure was associated with reduced activity in the prelimbic and medial orbitofrontal regions of the medial prefrontal cortex. Alcohol consumption was inversely related particularly to medial orbitofrontal activity.

Mechanism: Blocking nicotinic acetylcholine receptors reduced the nicotine-related increase in alcohol intake during some sessions.

Limitation: These findings are from mice and require human research before clinical conclusions can be drawn.

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Important issue but wrong solution

Publication type: This is a commentary by J. Robert Branston and Coral Gartner published in Addiction.

Context: PubMed keywords include Australia, enforcement, illicit products, nicotine, tobacco and vaping products/e-cigarettes. The paper references the wider debate about whether Australia has lost control of its tobacco and nicotine markets.

Limitation: PubMed provides no abstract. This explainer therefore does not invent or reconstruct the authors' specific arguments or preferred policy solution.

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Inhibiting CYP2A5 enzyme in mice decreases circulating cotinine after nicotine administration and increases dopamine in the brain

Purpose: Researchers examined whether inhibiting the mouse CYP2A5 enzyme could slow nicotine metabolism and alter brain dopamine levels.

Methods: Mice received nicotine with or without Ginkgo biloba, quercetin or 8-methoxypsoralen. Researchers measured serum cotinine, brain dopamine and liver CYP2A5 activity.

Results: 8-methoxypsoralen inhibited nicotine metabolism by approximately 55% and increased brain dopamine. Chronic Ginkgo biloba and quercetin did not detectably inhibit nicotine metabolism, although Ginkgo biloba increased dopamine.

Limitation: This was an experimental mouse study and does not establish safety or effectiveness of nicotine-metabolism inhibitors as smoking-cessation treatments in humans.

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High-Resolution Mass Spectrometric Analysis of Selected DNA Adducts in Smokeless Tobacco Users' Oral Cells

Background: Smokeless tobacco is an established cause of oral, oesophageal and pancreatic cancers. DNA adducts are considered important intermediates in carcinogenesis.

Methods: Researchers used high-resolution mass spectrometry to measure selected DNA adducts in oral cells from 24 smokeless tobacco users and 25 people who used no tobacco or nicotine products.

Results: Several adducts, including γ-OH-Acr-dGuo, γ-OH-Cro-dGuo and 7-Et-Gua, were significantly higher among smokeless tobacco users. Two other measured markers were not significantly different.

Conclusion: The study provides new human data showing substantial elevations of selected DNA adducts in oral cells associated with smokeless tobacco use.

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Differential Mutagenic Response of Rat Liver and Lung to Nicotine-Derived Nitrosamine Ketone (NNK)

Purpose: Researchers examined the mutagenic effects of nicotine-derived nitrosamine ketone, or NNK, in rat lung and liver tissue.

Methods: Big Blue rats received NNK at doses ranging from 0.001 to 30 mg/kg for 28 days. Genetic mutations were measured using two sequencing and mutation-detection approaches.

Findings: The no-genotoxic-effect level was 1 mg/kg in liver and 0.1 mg/kg in lung. Benchmark-dose analysis also indicated greater sensitivity of lung tissue. Mutation patterns differed between the two organs.

Limitation: This was an animal study designed for toxicology and risk-assessment research and does not directly establish human cancer risk.

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