Conventional and multi-omics assessments of subacute inhalation toxicity due to propylene glycol and vegetable glycerin aerosol produced by electronic cigarettes.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Effects of Aftermarket Electronic Cigarette Pods on Device Power Output and Nicotine, Carbonyl, and ROS Emissions.

Aftermarket pods designed to operate with prevalent electronic nicotine delivery system (ENDS) products such as JUUL are marketed as low-cost alternatives that allow the use of banned flavored liquids. Subtle differences in the design or construction of aftermarket pods may intrinsically modify the performance of the ENDS device and the resulting nicotine and toxicant emissions relative to the original equipment manufacturer's product. In this study, we examined the electrical output of a JUUL battery and the aerosol emissions when four different brands of aftermarket pods filled with an analytical-grade mixture of propylene glycol, glycerol, and nicotine were attached to it and puffed by machine. The aerosol emissions examined included total particulate matter (TPM), nicotine, carbonyl compounds (CCs), and reactive oxygen species (ROS). We also compared the puff-resolved power and TPM outputs of JUUL and aftermarket pods. We found that all aftermarket pods drew significantly greater electrical power from the JUUL battery during puffing and had different electrical resistances and resistivity. In addition, unlike the case with the original pods, we found that with the aftermarket pods, the power provided by the battery did not vary greatly with flow rate or puff number, suggesting impairment of the temperature control circuitry of the JUUL device when used with the aftermarket pods. The greater power output with the aftermarket pods resulted in up to three times greater aerosol and nicotine output than the original product. ROS and CC emissions varied widely across brands. These results highlight that the use of aftermarket pods can greatly modify the performance and emissions of ENDS. Consumers and public health authorities should be made aware of the potential increase in the level of toxicant exposure when aftermarket pods are employed.

Comprehensive characterization of volatile and semi-volatile compounds in e-liquids for electronic cigarette using gas chromatography accurate mass spectrometry.

The consumption of electronic cigarettes is a habit with an increasing prevalence, particularly among youths. Knowing the composition of e-liquids used in these devices represents the first step to understand the potential impact of e-smoking in the health of consumers. Herein, a non-target screening methodology was applied to the identification of volatile and semi-volatile compounds in a set of e-liquids from different suppliers, with different flavors, and containing different kinds of additives, such as nicotine or cannabidiol. To this end, samples were characterized by gas chromatography accurate mass spectrometry, using a time-of-flight mass analyzer. Combination of deconvoluted electronic ionization mass spectra with linear retention index values, obtained for two columns with different selectivity, permitted the identification of more than 250 chemicals with different confidence levels. Among them, respiratory pro-inflammatory compounds, acetals of propylene glycol and glycerin with aldehydes, nicotine-related and non-related alkaloids, and psychoactive cannabinoids were confirmed as concerning compounds in e-liquid samples. Concentration ratios between propylene glycol acetals and parent aldehydes varied in the range from 2% (ethyl vanillin) to more than 80% (case of benzaldehyde). The ratios between the concentrations of delta-9-tetrahydrocannabinol and cannabidiol in e-liquids stayed in the range from 0.02% to 0.3%.

Exposure, Retention, Exhalation, Symptoms, and Environmental Accumulation of Chemicals During JUUL Vaping.

Little is known about the chemical exposures that electronic cigarette (EC) users receive and emit during JUUL vaping and if exposures produce symptoms dose dependently. This study examined chemical exposure (dose), retention, symptoms during vaping, and the environmental accumulation of exhaled propylene glycol (PG), glycerol (G), nicotine, and menthol in a cohort of human participants who vaped JUUL "Menthol" ECs. We refer to this environmental accumulation as "EC exhaled aerosol residue" (ECEAR). Chemicals were quantified using gas chromatography/mass spectrometry in JUUL pods before and after use, lab-generated aerosols, human exhaled aerosols, and in ECEAR. Unvaped JUUL "Menthol" pods contained ∼621.3 mg/mL of G, ∼264.9 mg/mL of PG, ∼59.3 mg/mL of nicotine, ∼13.3 mg/mL of menthol, and ∼0.1 mg/mL of the coolant WS-23. Eleven experienced male EC users (aged 21-26) provided exhaled aerosol and residue samples before and after vaping JUUL pods. Participants vaped ad libitum for 20 min, while their average puff count (22 ± 6.4) and puff duration (4.4 ± 2.0) were recorded. The transfer efficiency of nicotine, menthol, and WS-23 from the pod fluid into the aerosol varied with each chemical and was generally similar across flow rates (9-47 mL/s). At 21 mL/s, the average mass of each chemical retained by the participants who vaped 20 min was 53.2 ± 40.3 mg for G, 18.9 ± 14.3 mg for PG, 3.3 ± 2.7 mg for nicotine, and 0.5 ± 0.4 mg for menthol, with retention deduced to be ∼90-100% for each chemical. There was a significant positive relationship between the number of symptoms during vaping and total chemical mass retained. ECEAR accumulated on enclosed surfaces where it could contribute to passive exposure. These data will be valuable to researchers studying human exposure to EC aerosols and agencies that regulate EC products.

Unraveling propylene glycol-induced lipolysis of the biosynthesis pathway in ultra-high temperature milk using high resolution mass spectrometry untargeted lipidomics and proteomics.

In July 2022, the food safety accident that excessive propylene glycol was detected in milk processing factory raised widespread concerns about quality and nutrition of milk with illegal additive. To the best of our knowledge, the influences of propylene glycol to lipids in milk had not been systematically explored. Therefore, spatiotemporal distributions of lipids related to propylene glycol reaction and changes of sensory quality were investigated by food exogenous. Briefly, 10 subclasses (Cer, DG, HexCer, LPC, LPE, PC, PE, PI, SPH and TG) included 147 lipids and 38 pivotal enzymes were annotated. Propylene glycol altered lysophospholipidase and phospholipase A2 through altering structural order in lipids domains surrounding proteins to inhibit glycerophospholipid metabolism and initiated obvious changes in PC (10.45-27.91 mg kg-1) and PE (12.92-49.02 mg kg-1). This study offered insights into influences of propylene glycol doses and storage time on milk metabolism at molecular level to assess the quality of milk.

Did JUUL alter the content of menthol pods in response to US FDA flavour enforcement policy?

BACKGROUND: The JUUL electronic cigarette (e-cigarette) remains popular in the USA and has a big prevalence among youth. In response to the popularity of JUUL and similar devices among youth, the US Food and Drug Administration issued in February 2020 an enforcement policy to remove all flavoured cartridge/pod-based e-cigarettes from the market except for tobacco and menthol. Subsequent studies showed that some users of the now-removed flavoured JUUL pods (especially cool mint) switched to menthol-flavoured JUUL pods with similar satisfaction. METHODS: We quantified menthol, nicotine, propylene glycol (PG) and vegetable glycerol (VG) in JUUL pod samples (Menthol, Classic Menthol and Cool Mint) that were purchased in 2017, 2018 and 2020 (only Menthol) to evaluate composition differences before and after the enforcement policy. We also analysed the samples to detect other cooling agents using a screening gas chromatography-mass spectrometry headspace method that we developed for this purpose. RESULTS: Menthol concentration was significantly higher in 2020 products than in products from prior years. Moreover, other cooling agents varied across pods. The PG/VG volume ratio was 27/63 in all pods examined. CONCLUSION: This study highlights how regulations intended to reduce e-cigarette prevalence among youth may influence changes in tobacco product characteristics in ways that regulators may not have foreseen.

Computational modeling method to estimate secondhand exposure potential from exhalations during e-vapor product use under various real-world scenarios.

Potential secondhand exposure of exhaled constituents from e-vapor product (EVP) use is a public health concern. We present a computational modeling method to predict air levels of exhaled constituents from EVP use. We measured select constituent levels in exhaled breath from adult e-vapor product users, then used a validated computational model to predict constituent levels under three scenarios (car, office, and restaurant) to estimate likely secondhand exposure to non-users. The model was based on physical/thermodynamic interactions between air, vapor, and particulate phase of the aerosol. Input variables included space setting, ventilation rate, total aerosol amount exhaled, and aerosol composition. Exhaled breath samples were analyzed after the use of four different e-liquids in a cartridge-based EVP. Nicotine, propylene glycol, glycerin, menthol, formaldehyde, acetaldehyde, and acrolein levels were measured and reported based on a linear mixed model for analysis of covariance. The ranges of nicotine, propylene glycol, glycerin, and formaldehyde in exhaled breath were 89.44-195.70 µg, 1199.7-3354.5 µg, 5366.8-6484.7 µg, and 0.25-0.34 µg, respectively. Acetaldehyde and acrolein were below detectable limits; thus, no estimated exposure to non-EVP users is reported. The model predicted that nicotine and formaldehyde exposure to non-users was substantially lower during EVPs use compared to cigarettes. The model also predicted that exposure to propylene glycol, glycerin, nicotine and formaldehyde among non-users was below permissible exposure limits.

Impact of glycol-based solvents on indoor air quality-Artificial fog and exposure pathways of formaldehyde and various carbonyls.

Artificial fog is commonly employed in the entertainment industry and indoor household celebrations. The fog is generated from glycol-based solvents, which can also be found in e-cigarettes and personal care products. Although potential health impacts of glycol inhalation are frequently cited by studies of e-cigarette smoking, the dynamics and the chemical composition of glycol-based aerosols have never been studied systematically. The objective of this work is to investigate the impact of glycol-based aerosol on indoor air quality. Specifically, we targeted artificial fogs generated with common glycols, including propylene glycol (PG) and triethylene glycol (TEG). With the aid of a novel aerosol collecting and monitoring instrument setup, we obtained time-resolved aerosol profiles and their chemical compositions in an experimental room. Artificial fog has given rise to a significant amount of ultra-fine particulate matter, demonstrating its negative impact on indoor air quality. Additionally, we found a high concentration (9.75 mM) of formaldehyde and other carbonyls in fog machine fluids stored for months. These compounds are introduced to the indoor air upon artificial fog application. We propose that carbonyls have accumulated from the oxidative decomposition of glycols, initiated by OH radicals and singlet oxygens (1 O2 ) and likely sustained by autooxidation. Oxidation of glycols by indoor oxidants has never been reported previously. Such chemical processes can represent an unrecognized source of toxic carbonyl compounds which is also applicable to other glycol-based solvents.

A Simple Method to Simultaneously Determine the Level of Nicotine, Glycerol, Propylene Glycol, and Triacetin in Heated Tobacco Products by Gas Chromatography-Flame-Ionization Detection.

BACKGROUND: Currently, there is no validated and available method internationally to determine the contents of nicotine and aerosolizing agents, namely glycerol and propylene glycol, added onto the heatsticks for use in heated smoking devices. OBJECTIVE: To determine the concentrations of nicotine, propylene glycol, glycerol and triacetin in heated tobacco products (HTPs) which is essential to understanding their health effects on smokers as well as secondhand smokers. METHODS: A simple methodology was developed and validated to simultaneously determine nicotine, propylene glycol, glycerol, and triacetin concentrations present in heatsticks. The tobacco material was extracted with a mixture of methanol-acetonitrile (7 + 3, by volume) with 1,3-butanediol and n-heptadecane as internal standards and analyzed with gas chromatography with flame-ionization detection (GC-FID). RESULTS: Good linearity was achieved over the following concentration ranges: 0.1-1.0 mg/mL for nicotine, 0.03-2.0 mg/mL for propylene glycol, 0.5-10.0 mg/mL for glycerol, and 0.1-4.0 mg/mL triacetin, with a coefficient of determination ≥0.995. The limits of detection and quantification were 0.0009 and 0.003 mg/mL for nicotine, 0.02 and 0.02 mg/mL for propylene glycol, 0.03 and 0.09 mg/mL for glycerol, and 0.005 and 0.02 mg/mL for triacetin, respectively. Good recoveries were obtained for nicotine at 89.8-102.0%, propylene glycol at 95.5-102.5%, glycerol at 95.2-102.6%, and triacetin at 90.6-103.1%. CONCLUSION: This method provides an affordable and reliable technique for routine analysis of nicotine and aerosolizing chemicals present in HTPs which is necessary to assess their impact to public health. HIGHLIGHTS: Many gaps remain in research on HTPs, in particular, country levels information on the content of the products are limited. This article contains information on a newly developed method to simultaneously determine nicotine, propylene glycol, glycerol and triacetin present in the tobacco material and butts of heatsticks for HTPs.

Electronic cigarette aerosol increases the risk of organ dysfunction by enhancing oxidative stress and inflammation.

An electronic cigarette is a rechargeable device that produces an inhaled aerosol containing varying levels of nicotine, and inorganic and organic toxicants and carcinogenic compounds. The aerosol is generated by heating a solution of propylene glycol and glycerin with nicotine and flavoring ingredients at a high temperature. The e-cigarette was developed and marketed as a safer alternative to the regular cigarette which is known to be injurious to human health. However, published studies suggest that the aerosol of e-cigarette can also have adverse health effects. The main objective of this review is to briefly describe some consequences of e-cigarette smoking, and to present data showing that the resulting increased oxidative stress and inflammation are likely to be involved in effecting to lung damage. Other organs are also likely to be affected. The aerosol contains varying amounts of organic and inorganic toxicants as well as carcinogens, which might serve as the source of such deleterious events. In addition, the aerosol also contains nicotine, which is known to be addictive. E-cigarette smoking releases these toxicants into the air leading to inhalation by nonsmokers in residential or work place areas. Unlike regular tobacco smoke, the long-term consequences of direct and secondhand exposure to e-cigarette aerosol have not been extensively studied but based on available data, e-cigarette aerosol should be considered harmful to human health.

Chemical analysis of fresh and aged Australian e-cigarette liquids.

OBJECTIVES: To assess the chemical composition of electronic cigarette liquids (e-liquids) sold in Australia, in both their fresh and aged forms. DESIGN, SETTING: Gas chromatography-mass spectrometry analysis of commercial e-liquids sold in Australia (online and physical stores). MAIN OUTCOME MEASURES: Chemical composition of 65 Australian e-liquids - excipients/solvents, flavouring chemicals, other known e-liquid constituents (including nicotine), and polycyclic aromatic hydrocarbons - before and after an accelerated ageing process that simulated the effects of vaping. RESULTS: The measured levels of propylene glycol and glycerol often diverged from those recorded on the e-liquid label. All e-liquids contained one or more potentially harmful chemicals, including benzaldehyde, menthol, trans-cinnamaldehyde, and polycyclic aromatic hydrocarbons. Nicotine or nicotyrine were detected in a small proportion of e-liquids at extremely low concentrations. CONCLUSIONS: Australian e-liquids contain a wide variety of chemicals for which information on inhalation toxicity is not available. Further analyses are required to assess the potential long term effects of e-cigarette use on health.

Ratio of Propylene Glycol to Glycerol in E-Cigarette Reservoirs Is Unchanged by Vaping As Determined by 1H NMR Spectroscopy.

E-cigarette liquids (e-liquids) contain propylene glycol (PG) and/or glycerol (GL) to deliver flavorants/nicotine. It has recently been suggested that the PG:GL ratio in e-cigarette reservoirs changes during vaping, leaving almost entirely GL after aerosolizing much of a 30:70 PG:GL mixture. To evaluate this directly, we analyzed e-liquids from e-cigarettes before and after aerosolization using 4 different coils, and aerosol samples generated using high and low e-liquid levels. The PG:GL ratios of initial and final e-liquids and aerosol samples were comparable. This is important because a large change in e-liquid composition could substantially alter the aerosol profile during a vaping session.

The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols.

In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests. Whilst informative on induction of a finite endpoint and relative risk posed by test articles, such assays could benefit from mechanistic supplementation. The ToxTracker and Aneugen Clastogen Evaluation analysis can indicate the activation of reporters associated with (geno)toxicity, including DNA damage, oxidative stress, the p53-related stress response and protein damage. Here, we tested for the different effects of a selection of neat e-liquids, EVP aerosols and Kentucky reference 1R6F cigarette smoke samples in the ToxTracker assay. The assay was initially validated to assess whether a mixture of e-liquid base components, propylene glycol (PG) and vegetable glycerine (VG) had interfering effects within the system. This was achieved by spiking three positive controls into the system with neat PG/VG or phosphate-buffered saline bubbled (bPBS) PG/VG aerosol (nicotine and flavour free). PG/VG did not greatly affect responses induced by the compounds. Next, when compared to cigarette smoke samples, neat e-liquids and bPBS aerosols (tobacco flavour; 1.6% freebase nicotine, 1.6% nicotine salt or 0% nicotine) exhibited reduced and less complex responses. Tested up to a 10% concentration, EVP aerosol bPBS did not induce any ToxTracker reporters. Neat e-liquids, tested up to 1%, induced oxidative stress reporters, thought to be due to their effects on osmolarity in vitro. E-liquid nicotine content did not affect responses induced. Additionally, spiking nicotine alone only induced an oxidative stress response at a supraphysiological level. In conclusion, the ToxTracker assay is a quick, informative screen for genotoxic potential and mechanisms of a variety of (compositionally complex) samples, derived from cigarettes and EVPs. This assay has the potential for future application in the assessment battery for next-generation (smoking alternative) products, including EVPs.

Room air constituent concentrations from use of electronic nicotine delivery systems and cigarettes using different ventilation conditions.

To assess potential exposure of non-users to exhaled constituents from pod and cartridge electronic nicotine delivery systems (ENDS) products, an environmental clinical study was conducted with (n = 43) healthy adult smokers. Room air concentrations of 34 selected constituents (nicotine, propylene glycol, glycerin, 15 carbonyls, 12 volatile organic compounds, and 4 trace metals) and particle number concentration (0.3 to 25 µm) were compared from use of two ENDS products and conventional cigarettes using room ventilations representative of a residential, an office or a hospitality setting over a 4-h. exposure period. Products used were JUUL ENDS, Virginia Tobacco flavor (Group I), VUSE Solo, Original flavor (Group II) (5.0 and 4.8% nicotine by weight, respectively) and subjects' own conventional cigarettes (Group III). Cumulative 4-h room air sampling and particle counting were performed during prescribed (Groups I and II) and ad libitum product use (all Groups). Conventional cigarette use resulted in significantly more constituents detected and higher 4-h cumulative constituent concentrations compared to use of the ENDS products tested, except for the predominant ENDS ingredients, propylene glycol and glycerin. Use of conventional cigarettes also resulted in greater total particle number concentration than either prescribed or ad libitum use of either of the ENDS used in this study.

Effects of Lactobacillus hilgardii 4785 and Lactobacillus buchneri 40788 on the bacterial community, fermentation and aerobic stability of high-moisture corn silage.

AIMS: To evaluate the capacity of Lactobacillus hilgardii and Lactobacillus buchneri on modifying the bacterial community and improving fermentation and aerobic stability of high-moisture corn (HMC). METHODS AND RESULTS: High-moisture corn was untreated (CTR), treated with L. hilgardii (LH) or L. buchneri (LB) at 600 000 CFU per gram fresh weight, or with L. hilgardii and L. buchneri at 300 000 CFU per gram fresh weight each (LHLB), and stored for 10, 30 or 92 days. Compared to CTR, inoculated silages had higher Lactobacillaceae relative abundance, lower yeasts numbers and higher aerobic stability. Treatment with LHLB resulted in a higher acetic acid concentration than LH and higher 1,2 propanediol concentration than LB, such differences were numerically greater at 10 and 30 days but statistically greater at 92 days. At 10 days, all inoculated silages were more stable than CTR, but LHLB was even more stable than LB or LH. CONCLUSIONS: The combination of L. hilgardii and L. buchneri had a synergistic effect on yeast inhibition, leading to greater improvements in aerobic stability as early as 10 days after ensiling. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus hilgardii, especially in combination with L. buchneri, can improve the aerobic stability of HMC after a very short period of ensiling.

A comparison of the electrical characteristics, liquid composition, and toxicant emissions of JUUL USA and JUUL UK e-cigarettes.

In 2018, JUUL entered the UK market, where EU regulations limit liquid nicotine concentration to 20 mg/mL, approximately one-third the level of JUUL products sold in the USA. We hypothesized that JUUL's UK product was engineered to deliver greater electrical power and boost liquid vaporization such that the net nicotine delivery rate was similar to the US version. We compared electrical characteristics, liquid composition, and aerosol emissions of JUUL devices procured in the USA and the UK. Study outcomes included electrical power, total and freebase nicotine, propylene glycol/vegetable glycerin ratio, carbonyls, and reactive oxygen species. Liquids and aerosols were analyzed by GCMS, HPLC, and fluorescence. Compared to the US version, JUUL UK had approximately one-third the liquid nicotine concentration in the liquid (5.4 vs. 1.6 wt.%) and aerosol (4.7 and 1.3 wt.%). Other than nicotine concentration and yield, we found no differences in any other study outcome, including electrical power. Currently, JUUL UK emits nicotine at a far lower rate than the US product, offering an opportunity to study how this factor impacts user behavior, JUUL uptake, and other population-level outcomes across the two markets.

Determination of Thermal Decomposition Products Generated from E-Cigarettes.

An electronic cigarette (e-cigarette) is a product used to smoke aerosol by heating a solution of "e-liquid" that consists of propylene glycol (PG) and glycerol (GLY) containing nicotine and flavors. In this study, thermal decomposition products generated from three brands of e-cigarettes were determined at various electric power levels. When using neat PG or GLY instead of e-liquid, propylene oxide was detected only in the gas phase from PG and not detected from GLY. In contrast, glycidol was detected only from GLY and not from PG. Almost all of the glyoxal and acrolein was detected from GLY, but formaldehyde and methyl glyoxal were detected from both PG and GLY. Using commercially available e-liquids, the same results were obtained. Nearly all chemical compounds generated from e-cigarettes have a carbon number of 3 or less except for nicotine and flavors. We measured chemical compounds generated from e-cigarettes at various electric power levels (1-85 W). At an electric power of 10 W, the generation of chemical compounds was very low; however, when the electric power exceeded 40 W, it increased exponentially. As thermal decomposition products of e-liquid, acetaldehyde, acrolein, and propylene oxide mainly occur as gaseous matter, while glyoxal, methylglyoxal, and glycidol mainly occur as particulate matter. Formaldehyde exits in both gaseous and particulate matter forms. Thermal decomposition products can be divided into three groups: thermal decomposition products originating from PG and GLY, those originating from other sources, and those directly generated. Concentrations of these thermal decomposition products were mostly higher than those in traditional cigarettes. In particular, thermal decomposition products generated from one of the studied e-cigarettes were very high; e.g., formaldehyde reached 4400 µg/15 puffs at 50 W. E-cigarette users must know that hazardous substances are generated even within the recommended electric power limits.

Natural deep eutectic solvents and aqueous solutions as an alternative extraction media for propolis.

Ethanolic extracts of propolis are consumed for their health benefits even though direct consumption of alcoholic extracts is not always ideal. Natural Deep Eutectic Solvents (NADES) can potentially extract similar compounds as alcoholic extracts while being better for direct consumption. Therefore, in this work alternative solvents for the extraction of green propolis including its biomarker artepillin C were examined. Sixteen NADES made from low toxicity chemicals, including the essential amino acid l-lysine, were explored along with twelve individual NADES components and honey, which showed similar physical-chemical properties to NADES. At 50 °C NADES made from choline chloride-propylene glycol or lactic acid proved to be equal or better than the benchmark EtOH:Water 7:3 (v/v). Alternatively, aqueous l-lysine appeared as a potential solvent for the preparation of aqueous propolis extracts. From these findings NADES, honey and aqueous l-lysine solutions all demonstrated the potential to replace ethanol or water for extracting green propolis.

Identification of non-volatile migrants from baby bottles by UPLC-Q-TOF-MS.

Baby bottles made of polypropylene, Tritan® and silicone were evaluated regarding the migration of non-volatile compounds using UPLC-QTOF-MS. Twenty-seven compounds were identified. In all polypropylene samples the migration of 2.2'-(tridecylimino)bis-ethanol and derivatives thereof were detected in concentrations below the specific migration limit (1.2 mg.kg-1). Furthermore, clarifying agents and glycerol derivatives were detected. Tritan baby bottle showed the migration of one slip additive. On the other hand, twenty compounds were detected in silicone baby bottles. Most of them were unknown compounds derived from acrylates. Once the migrants were identified, the risk assessment was carried out using the Threshold of Toxicological Concern (TTC) approach. The risk assessment of migrants coming from silicone samples showed levels above the threshold recommended as safe for babies.

Prevalence of ethanol and other potentially harmful excipients in pediatric oral medicines: survey of community pharmacies in a Nigerian City.

OBJECTIVE: Excipients are needed in the formulation of oral liquid medicines intended for children; they have however been reported to trigger safety issues. This study evaluated the concentrations and prevalence of ethanol and other potentially harmful excipients in pediatric formulations marketed in South Eastern Nigeria in line with international labeling guidelines and allowable daily limits (ADL). The study sampled oral pediatric formulations offered for sale in registered pharmacies. Those with accessible information leaflets were assessed for the presence and quantity of previously flagged excipients with potential to harm the pediatric population. RESULT: Of the 380 oral pediatric medicines, 140 provided access to list/quantity of ingredients. 47.9% (67) of the formulations contain at least one of the flagged excipients while the remaining only listed the active ingredients. Ethanol had the highest occurrence (62.7%) and was more in cough/cold medicines. A homeopathic cough and cold remedy had concentration of 90% v/v. Ethanol and sucrose in some formulations exhibited concentrations with a potential of crossing their approved daily intake (ADI) (1-90% v/v and 1.7 g-3.7 g/5 ml respectively). Ethanol use in studied pediatric formulations was quite high, with ethanol-containing formulations being prescribed for children 0-6 years and older. Only 26 (38.8%) completely satisfied the labelling requirements for ethanol containing formulations.