Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution rather than smoke and without tobacco combustion. Perceived as a safer alternative to conventional cigarettes, e-cigs are aggressively marketed as lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory guidelines. E-cigs have also gained popularity among never-smokers and teenagers, becoming an emergent public health issue. Despite the burgeoning worldwide consumption of e-cigs, their safety remains largely unproven and it is unknown whether these devices cause in vivo toxicological effects that could contribute to cancer. Here we demonstrate the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat lung model. We found that e-cigs have a powerful booster effect on phase-I carcinogen-bioactivating enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), and increase oxygen free radical production and DNA oxidation to 8-hydroxy-2′-deoxyguanosine. Furthermore, we found that e-cigs damage DNA not only at chromosomal level in peripheral blood, such as strand breaks in leucocytes and micronuclei formation in reticulocytes, but also at gene level such as point mutations in urine. Our results demonstrate that exposure to e-cigs could endanger human health, particularly among younger more vulnerable consumers.

Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.

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