Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices.

Users of e-cigarettes are unwitting volunteers participating in a worldwide epidemiological study. Because of the obvious benefits of e-cigarettes compared with traditional cigarette smoking, these electronic devices have been introduced all around the world to support tobacco smoking cessation. Same potential harm reduction could be considered by cannabis vaping for marijuana smokers. However, the toxicities of liquids and aerosols remain under investigation because although the use of e-cigarettes is likely to be less harmful than traditional cigarette smoking, trace levels of contaminants have been identified. Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e-pipes, have been developed and commercialised. Consequently, misuse of electronic devices has increased, and experimentation has been documented on Internet web fora. Although legal and illegal drugs are currently consumed with these e-devices, no scientific papers are available to support the observations reported by numerous media and web fora. Moreover, building on illegal drug vaping and vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative use of vaping) could present therapeutic benefits, as occurs with medical cannabis vaporisation with table vaporisers. This review seeks to synthesise the problems of e-cigarette and liquid refill toxicity in order to introduce the dangers of illegal and legal drugs consumed using vaping and vaporisation for recreational purposes, and finally, to present the potential therapeutic benefits of vaping as a new administration route for legal drugs

Carbon monoxide analysis method in human blood by Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS): Relevance for postmortem poisoning diagnosis.

Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 μmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 μmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings

Confirmation of natural gas explosion from methane quantification by headspace gas chromatography-mass spectrometry (HS-GC-MS) in postmortem samples: a case report

A new analytical approach for measuring methane in tissues is presented. For the first time, the use of in situ-produced, stably labelled CDH3 provides a reliable and precise methane quantification. This method was applied to postmortem samples obtained from two victims to help determine the explosion origin. There was evidence of methane in the adipose tissue (82nmol/g) and cardiac blood (1.3nmol/g) of one victim, which corresponded to a lethal methane outburst. These results are discussed in the context of the available literature to define an analysis protocol for application in the event of a gas explosio

Total Blood Carbon Monoxide: Alternative to Carboxyhemoglobin as Biological Marker for Carbon Monoxide Poisoning Determination.

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 μmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 μmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses

A fatal case of oxygen embolism in a hospital

This case reports on a 68-year-old man who was found dead in hospital next to his bed. Before this, he had been treated with intravenous antibiotics for pneumonia. The body was found with a peripheral venous catheter connected to a nasal cannula delivering oxygen (O2) from the wall. Extensive medico–legal examinations were performed, including post-mortem computed tomography (CT), complete conventional autopsy, histological and immunohistochemistry analysis, toxicological analysis and post-mortem chemistry. Additionally, CT-guided gas sampling was performed at multiple sites to collect samples for gas analysis. During the external examination, massive subcutaneous emphysema was visible over the entire surface of the body. The CT scan revealed the presence of gas throughout the vascular system, and in the subcutaneous and muscular tissues. The autopsy confirmed the presence of lobar pneumonia and multiple gas bubbles in the vascular system. The gas analysis results showed a subnormal concentration of oxygen, confirming the suspected pure O2 embolism. Moreover, the carbon dioxide (CO2) concentration in the gas sample from the heart was elevated to a level similar to those found in scuba diving fatalities. This could come from degassing of dissolved CO2 that accumulated and was trapped in the cardiac cavity. Based on the results of the different exams performed, and especially the gas analysis results, it was concluded that the cause of death was O2 embolism

Stability of postmortem methemoglobin: Artifactual changes caused by storage conditions.

Hemoglobin is the protein in red blood cells that carries and distributes oxygen to the body. Methemoglobinemia is a blood disorder in which an abnormal amount of methemoglobin (MetHb), a form of hemoglobin (Hb), is produced from either inadequate MetHb reductase activity or too much MetHb production or by exposure to oxidizing agents. This could lead to anoxia and death if it is not treated. However, this parameter has not been investigated as a valid post-mortem indicator because random MetHb levels have been observed in various studies: MetHb increases can be observed due to autoxidation during storage, and MetHb decreases can be observed due to MetHb reductase or microbial activity in post-mortem samples. MetHb variations can also come from the blood state and can interfere in the optical measurements of MetHb. We have studied the post-mortem MetHb concentrations according to various storage conditions. Based on our results, both the post-mortem delay and the delay before analysis should be reduced whenever possible to avoid changes in MetHb. If the analysis is delayed for a short period of time (two weeks), the blood sample taken at autopsy should not be frozen but collected in EDTA preservative and stored under refrigeration (4-6°C) until analysis. If the analysis is delayed for a longer period (more than two weeks), the blood sample should be frozen with cryoprotectant at -80°C or -196°C

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure

Accuracy profile validation of a new analytical method for propane measurement using headspace-gas chromatography-mass spectrometry

Propane can be responsible for several types of lethal intoxication and explosions. Quantifying it would be very helpful to determine in some cases the cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of propane measurements do already exist. The main drawback of these GC-MS methods described in the literature is the absence of a specific propane internal standard necessary for accurate quantitative analysis. The main outcome of the following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS) applicable to the routine determination of propane concentration in forensic toxicology laboratories. To date, no stable isotope of propane is commercially available. The development of an in situ generation of standards is thus presented. An internal-labeled standard gas (C3DH7) is generated in situ by the stoichiometric formation of propane by the reaction of deuterated water (D2O) with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use this internal standard to quantify propane concentrations and, therefore, to obtain precise measurements. Consequently, a complete validation with an accuracy profile according to two different guidelines, the French Society of Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft für toxikologische und Forensische Chemie (GTFCh), is presented

Changes in aroma and sensory profile of food ingredients smoked in the presence of a zeolite filter

During smoking, formation of desirable smoky compounds and carcinogenic polycyclic aromatic hydrocarbons (PAH) are inextricably linked. We have previously developed a zeolite filter technology (PureSmoke Technology or PST) that reduces the PAH content of a smoke stream, particularly reducing the concentration of benzo[a]pyrene, a known carcinogen, by up to 93%. The aim of this work was to determine whether there were changes in the volatile and sensory profiles of ingredients smoked using PST compared to the traditional smoking process (Trad). Smoked tomato flakes (either PST or Trad) were added to either low-fat or full-fat cream cheese for sensory profiling and consumer preference tests, and volatile analysis was carried out using solid phase microextraction (SPME) followed by gas chromatography-mass spectrometry (GC-MS). The sensory analysis showed a significant decrease (p < 0.01) in bitterness when the PST was employed and a significant decrease in overall smoky aroma and flavor (p < 0.001), which resulted in an increase in the perception of cheesy aroma and flavor. This was consistent with a decrease in many of the smoky aroma compounds, particularly the guaiacols. However, consumer preference tests showed that there was no adverse effect on the flavor of the products, and there was even a tendency for the PST product to be preferred to the Trad product (p = 0.096). The smoke compounds were quantitated and compared in smoked tomato paste. Odor activity values (OAVs) calculated from the literature thresholds suggested that guaiacol and 4-alk(en)yl-substituted guaiacols are likely to be among the most highly odor-active compounds in these smoked ingredients

Sonocrystallisation of ZIF-8 in water with high excess of ligand: Effects of frequency, power and sonication time

A systematic study on the sonocrystallisation of ZIF-8 (zeolitic imidazolate framework-8) in a water-based system was investigated under different mixing speeds, ultrasound frequencies, calorimetric powers and sonication time. Regardless of the synthesis technique, pure crystals of ZIF-8 with high BET (Brunauer, Emmett and Teller) specific surface area (SSA) can be obtained in water after only 5 s. Furthermore, 5 s sonication produced even smaller crystals (~0.08 µm). The type of technique applied for producing the ZIF-8 crystals did not have any significant impact on crystallinity, purity and yield. Crystal morphology and size were affected by the use of ultrasound and mixing, obtaining nanoparticles with a more spherical shape than in silent condition (no ultrasound and mixing). However, no specific trends were observed with varying frequency, calorimetric power and mixing speed. Ultrasound and mixing may have an effect on the nucleation step, causing the fast production of nucleation centres. Furthermore, the BET SSA increased with increasing mixing speed. With ultrasound, the BET SSA is between the values obtained under silent condition and with mixing. A competition between micromixing and shockwaves has been proposed when sonication is used for ZIF-8 production. The former increases the BET SSA, while the latter could be responsible for porosity damage, causing a decrease of the surface area. © 2021 The Author(s