E-cigarette Refill Liquids Research Articles

Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats

BackgroundThe popularity of electronic cigarettes (ECs) has increased dramatically despite their unknown health consequences. Because the abuse liability of ECs is one of the leading concerns of the Food and Drug Administration (FDA), models to assess it are urgently needed to inform FDA regulatory decisions regarding these products. The purpose of this study was to assess the relative abuse liability of an EC liquid compared to nicotine alone in rats. Because this EC liquid contains non-nicotine constituents that may enhance its abuse liability, we hypothesized that it would have greater abuse liability than nicotine alone. MethodsNicotine alone and nicotine dose-equivalent concentrations of EC liquid were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, acquisition of self-administration, reinforcing efficacy (i.e., elasticity of demand), blockade of these behavioral effects by mecamylamine, nicotine pharmacokinetics and nicotinic acetylcholine receptor binding and activation. ResultsThere were no significant differences between formulations on any measure, except that EC liquid produced less of an elevation in ICSS thresholds at high nicotine doses. ConclusionsCollectively, these findings suggest that the relative abuse liability of this EC liquid is similar to that of nicotine alone in terms of its reinforcing and reinforcement-enhancing effects, but that it may have less aversive/anhedonic effects at high doses. The present methods may be useful for assessing the abuse liability of other ECs to inform potential FDA regulation of those products.

Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats

The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 μl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela’s inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out.

Impact of electronic-cigarette refill liquid on rat testis

Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17βHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.

Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats

This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.

Impact of e-cigarette refill liquid exposure on rat kidney

Electronic-cigarettes (e-cigarette), the alternative to classic cigarettes are becoming extremely popular but their safety is not still established. Recent studies have showed cytotoxic effects of the electronic cigarette and its recharge e-liquid, in vitro. The present study was designed to evaluate e-cigarette liquid nephrotoxicity in rats. For this purpose, 32 rats were treated for 28 days as follows: Control group was injected intraperitoneally with NaCl 9 g/l; e-cigarette 0% treated group received an intraperitoneal injection of e-liquid without nicotine diluted in NaCl 9 g/l, e-cigarette treated group, received an intraperitoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l and nicotine-treated group received an intraperitoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l. In nicotine group, creatinine level was increased, whereas urea and acid uric levels were decreased. In e-liquid-exposed groups, levels of uric acid and mainly urea were lower. Interestingly, after e-liquid exposure, oxidative stress status showed increased total protein and sulfhydril content, whereas superoxide dismutase and catalase activities were decreased. However, the levels of lipid peroxides were not increased after e-liquid exposure. Histological studies identified excess of cells with reduced and dark nuclei exclusively located in the renal collecting ducts. Thus, e-liquid seems to alter anti-oxidant defense and to promote minor changes in renal function parameters. This preliminary study raises some flags about possible nephrotoxicity of e-cigarette liquids in rats. As some features observed in rats may not be observed in human smokers, additional studies are needed to further qualify conclusions that might be applicable to actual users of e-cigarettes.

Transdermal nicotine absorption handling e-cigarette refill liquids

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm2/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm2 corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm2. Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids.

New solid surface fluorescence methodology for lead traces determination using rhodamine B as fluorophore and coacervation scheme: Application to lead quantification in e-cigarette refill liquids

A new environmental friendly methodology based on fluorescent signal enhancement of rhodamine B dye is proposed for Pb(II) traces quantification using a preconcentration step based on the coacervation phenomenon. A cationic surfactant (cetyltrimethylammonium bromide, CTAB) and potassium iodine were chosen for this aim. The coacervate phase was collected on a filter paper disk and the solid surface fluorescence signal was determined in a spectrofluorometer. Experimental variables that influence on preconcentration step and fluorimetric sensitivity have been optimized using uni-variation assays. The calibration graph using zero th order regression was linear from 7.4×10−4 to 3.4μgL−1 with a correlation coefficient of 0.999. Under the optimal conditions, a limit of detection of 2.2×10−4μgL−1 and a limit of quantification of 7.4×10−4μgL−1 were obtained. The method showed good sensitivity, adequate selectivity with good tolerance to foreign ions, and was applied to the determination of trace amounts of Pb(II) in refill solutions for e-cigarettes with satisfactory results validated by ICP-MS. The proposed method represents an innovative application of coacervation processes and of paper filters to solid surface fluorescence methodology.