Aurélie Berthet

E-Cigarettes: A Review of New Trends in Cannabis Use

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely “vape” deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination.

Heat-Not-Burn Tobacco Cigarettes: Smoke by Any Other Name

Heat-Not-Burn Tobacco Cigarettes: Smoke by Any Other Name The tobacco industry’s most recent response to the documented harms of cigarette smoking was to launch new heatnot-burn (HNB) tobacco cigarettes.1 Philip Morris International (PMI) created IQOS (I-Quit-Ordinary-Smoking): disposable tobacco sticks soaked in propylene glycol, which are inserted in a holder in the HNB cigarette. The tobacco is heated with an electric blade at 350°C. The cigarettes are marketed by PMI as a “revolutionary technology that heats tobacco without burning it, giving you the true taste of tobacco, with no smoke, no ash and less smell.”2 In many countries, laws that protect people from passive smoke only apply to smoked tobacco products. Philip Morris International claims that IQOS releases no smoke because the tobacco does not combust and the tobacco leaves are only heated not burned. However, there can be smoke without fire. The harmful components of tobacco cigarette smoke are products of incomplete combustion (pyrolysis) and the degradation of tobacco cigarettes through heat (thermogenic degradation). Complete combustion occurs at a high temperature (>1300°C), higher than the heat generated by smoking a tobacco cigarette (<800°C). Typical markers of pyrolysis and thermogenic degradation of tobacco cigarettes are acetaldehyde, an irritant carcinogenic volatile organic compound, benzo[a]pyrene, a carcinogenic polycyclic aromatic hydrocarbon, and carbon monoxide. Pilot programs for IQOS began in 2014 in Japan and in 2015 in Switzerland and Italy. An internet survey in Japan published in 2015 suggested that younger individuals (15 to 39 years of age) were more likely to use IQOS, as were former smokers and current smokers.3 Since 2016, a total of 19 countries have allowed the sale of IQOS cigarettes. In June 2016, data from PMI revealed that IQOS had captured 2.2% of the cigarette market in Japan. IQOS is not yet sold in the United States, but in December 2016, PMI submitted a modified risk tobacco product application to the US Food and Drug Administration. If successful, PMI will be less restricted in its marketing for the IQOS than for conventional tobacco cigarettes. Smokers and nonsmokers need accurate information about toxic compounds released in IQOS smoke. This information should come from sources independent of the tobacco industry, but the only analyses we found were from PMI and PMI competitors.1 Methods | We compared the contents of IQOS (IQOS Holder, IQOS Pocket Charger, Marlboro HeatSticks [regular], and Heets, Philipp Morris SA) smoke with the contents of conventional cigarettes (Lucky Strike Blue Lights). We used a smoking device designed and tested in our facility to capture the mainstream aerosol and developed to meet standards for common cigarettes and e-cigarettes.4 We followed the International Organization for Standardization standards for puff volume (35 mL) at 2 puffs per minute, based on observation of IQOS smokers, who took a mean of 14 puffs during 5 to 6 minutes. We analyzed volatile organic compounds and nicotine by gas chromatography coupled to a flame ionization detector and polycyclic aromatic hydrocarbons using high-performance liquid chromatography coupled to a fluorescence detector, as previously described.4 We trapped polycyclic aromatic hydrocarbons from IQOS cigarette smoke in a glass filter (Whatman 37 mm Ø GF/B) mounted in line with an XAD2 cartridge. For each sampling, 10 IQOS cigarettes were smoked. Each sampling support was desorbed in 10 mL of acetonitrile and sonicated for 1 hour. The eluate was evaporated in a vacuum concentrator (Speed Vac SC-200, ThermoFisher Scientific) set with 30 millibars and 27g until the residue was almost dry to prevent evaporation of the most volatile polycyclic aromatic hydrocarbons. The residue was filtered with polytetrafluoroethylene membrane (Acrodisc CR 13 mm, 0.45 μm, Pall Life Sciences) before it was analyzed with a high-performance liquid chromatography device (Ultimate 3000, ThermoFisher Scientific) equipped with a fluorescence detector (FLD3000RS), UV detector (VWD-3000), and a separation column Nucleodur EC 150 × 3 mm C18 3 μm (Macherey-Nagel) under isocratic conditions (1.2 mL · min−1). We injected 2 μL into the high-performance liquid chromatography chain; methanol/ water (70/30) with acetonitrile was the eluent solvent at an initial ratio of 100% to 0% (4 minutes) and a linear gradient up to 100% acetonitrile (12 minutes). We did not analyze polycyclic aromatic hydrocarbons generated by conventional cigarettes and present the mean values in the 35 best-selling cigarettes brands in the United States, as reported by Vu et al.5 We monitored the temperature near the heater blade inside the IQOS holder and the core of the conventional cigarette at a sampling rate of 3 Hz with a type k thermocouple.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

In Vitro and In Vivo Effectiveness of an Innovative Silver-Copper Nanoparticle Coating of Catheters to Prevent Methicillin-Resistant Staphylococcus aureus Infection

ABSTRACT In this study, silver/copper (Ag/Cu)-coated catheters were investigated for their efficacy in preventing methicillin-resistant Staphylococcus aureus (MRSA) infection in vitro and in vivo. Ag and Cu were sputtered (67/33% atomic ratio) on polyurethane catheters by direct-current magnetron sputtering. In vitro, Ag/Cu-coated and uncoated catheters were immersed in phosphate-buffered saline (PBS) or rat plasma and exposed to MRSA ATCC 43300 at 104 to 108 CFU/ml. In vivo, Ag/Cu-coated and uncoated catheters were placed in the jugular vein of rats. Directly after, MRSA (107 CFU/ml) was inoculated in the tail vein. Catheters were removed 48 h later and cultured. In vitro, Ag/Cu-coated catheters preincubated in PBS and exposed to 104 to 107 CFU/ml prevented the adherence of MRSA (0 to 12% colonization) compared to uncoated catheters (50 to 100% colonization; P < 0.005) and Ag/Cu-coated catheters retained their activity (0 to 20% colonization) when preincubated in rat plasma, whereas colonization of uncoated catheters increased (83 to 100%; P < 0.005). Ag/Cu-coating protection diminished with 108 CFU/ml in both PBS and plasma (50 to 100% colonization). In vivo, Ag/Cu-coated catheters reduced the incidence of catheter infection compared to uncoated catheters (57% versus 79%, respectively; P = 0.16) and bacteremia (31% versus 68%, respectively; P < 0.05). Scanning electron microscopy of explanted catheters suggests that the suboptimal activity of Ag/Cu catheters in vivo was due to the formation of a dense fibrin sheath over their surface. Ag/Cu-coated catheters thus may be able to prevent MRSA infections. Their activity might be improved by limiting plasma protein adsorption on their surfaces.

Drug vaping applied to cannabis: Is “Cannavaping” a therapeutic alternative to marijuana?

Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoids forms can be used. Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas, and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of “cannavaping,” defined as the “vaping” of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids. The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively. Conversely, “therapeutic cannavaping” could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.

A new alternative method for testing skin irritation using a human skin model: A pilot study☆

BACKGROUND Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. OBJECTIVES To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). METHODOLOGY Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). RESULTS We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). CONCLUSIONS This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.

A systematic review of passive exposure to cannabis

Passive exposure to cannabis smoke may induce effects on behavior and psychomotor skills, and have legal consequences, including the risk of being falsely considered as a cannabis user. This can become a concern, especially in occupational contexts or when driving vehicles. In order to enable a differentiation between a passive and an active exposure to cannabis and to limit the likeliness to be detected positive following passive exposure, this review identified specific biomarkers of passive exposure in urine, blood, oral fluid, hair, and sebum. Out of 958 papers identified on passive exposure to cannabis, 21 were selected. Although positive tests had been observed in all matrices following extremely high passive exposure, some distinctive features were observed in each matrix compared to cannabis active use. More specifically, in everyday life conditions, 11-nor-delta-9-THC-carboxylic acid (THC-COOH) urinary level should be detected below the positivity threshold used to confirm active smoking of cannabis, especially after normalization to creatinine level. Measuring delta-9-tetrahydrocannabinol (THC) and THC-COOH in blood is an appropriate alternative for appraising passive exposure as low and very low concentrations of THC and THC-COOH, respectively, should be measured. In hair, oral fluid (OF) and sweat/sebum emulsion, no THCCOOH should be detected. Its presence in hair argues for regular cannabis consumption and in OF or sweat for recent consumption. The experts should recommend to persons who have to demonstrate abstinence from cannabis to avoid heavily smoky and unventilated environments.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME).

UNLABELLED Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. AIMS (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. METHODS Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. RESULTS Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. CONCLUSION Age is a factor that should be considered when biological limit values are developed.

Effectiveness of hand washing on the removal of iron oxide nanoparticles from human skin ex vivo

ABSTRACT In this study, the effectiveness of washing with soap and water in removing nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (α-Fe2O3) or maghemite (γ-Fe2O3) powder, with primary particle diameters between 20–30 nm, were applied to two samples each of fresh and frozen ex vivo human skin in two independent experiments. The permeation of nanoparticles through skin, and the removal of nanoparticles after washing with soap and water were investigated. Bare iron oxide nanoparticles remained primarily on the surface of the skin, without penetrating beyond the stratum corneum. Skin exposed to iron oxide nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively, of the original dose after washing. In the event of dermal exposure to chemicals, removal is essential to avoid potential local irritation or permeation across skin. Although manufactured at an industrial scale and used extensively in laboratory experiments, limited data are available on the removal of engineered nanoparticles after skin contact. Our finding raises questions about the potential consequences of nanoparticles remaining on the skin and whether alternative washing methods should be proposed. Further studies on skin decontamination beyond use of soap and water are needed to improve the understanding of the potential health consequences of dermal exposure to nanoparticles.